From owner-ageing@net.bio.net Sun Jan 01 22:00:00 1995 Path: biosci!internet!biosci!not-for-mail From: biohelp (BIOSCI Administrator) Newsgroups: bionet.molbio.ageing Subject: UNSUBSCRIBING, BIOSCI ARCHIVES, ADDRESS DATABASE & BIOSCI FAQ Date: 1 Jan 1995 02:00:08 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 338 Sender: daemon@net.bio.net Distribution: world Message-ID: <199501011000.CAA09570@net.bio.net> Four important items follow: How to cancel e-mail subscriptions to BIOSCI newsgroups, BIOSCI archive searching, the BIOSCI FAQ, and the BIOSCI User Address Directory form. If you have not yet listed yourself in our BIOSCI user directory, please take a few minutes to complete and return the form below. If your personal information has changed since you listed yourself, please send us a complete new updated form. We can not make manual revisions to existing entries. Sincerely, Dave Kristofferson BIOSCI/bionet Manager biosci-help@net.bio.net **** How to cancel a BIOSCI e-mail subscription **** If you want to cancel your e-mail subscription to this group, PLEASE DO NOT POST YOUR UNSUBSCRIBE REQUEST TO THE NEWSGROUP ADDRESS (NOR REPLY TO A MESSAGE POSTED TO THE NEWSGROUP)!!! This would send your request to all of the readers of the newsgroup, but it might still not be seen by the BIOSCI staff - thus you would annoy many people and possibly not accomplish your goal anyway. IF YOU ARE LOCATED IN THE AMERICAS OR PACIFIC RIM COUNTRIES, please send a message to biosci@net.bio.net Instructions on how to subscribe/unsubscribe will be returned automatically, so the contents of your message do not matter. IF YOU ARE LOCATED IN EUROPE, AFRICA OR CENTRAL ASIA, please send a message to MXT@dl.ac.uk containing the word help in the body of the message to retrieve e-mail server instructions. 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We maintain three indexes which are searchable from the main gopher menu on net.bio.net: (1) an index of all BIOSCI postings; (2) an index of individual journal article references from the Table of Contents postings on the BIO-JOURNALS newsgroup; and (3) an index of BIOSCI users including regular mail and e-mail addresses, phone/FAX numbers, research interests, and newsgroup participation. E-mail users can search the BIOSCI archives by using our waismail e-mail server. For instructions send the message help to waismail@net.bio.net. Leave the Subject: line blank (anything entered on the Subject: line is ignored). WAIS software can also be used to search the archives as described in the BIOSCI FAQ (see below). 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Thanks again for your cooperation! --------------- please cut here and return portion below --------------- New information or Update to old record (enter N or U): date (DD-MM-YY): first name: middle initial: family name: job title: e-mail address: e-mail network: phone number: FAX number: institution: address1: address2: address3: city: state/province: country: postal code: research interest: research interest: comment: comment: comment: comment: comment: From owner-ageing@net.bio.net Sun Jan 01 22:00:00 1995 Path: biosci!daresbury!sunsite.doc.ic.ac.uk!agate!howland.reston.ans.net!news1.digex.net!news.iac.net!news From: ren@iac.net (John Thomas Renfro) Newsgroups: bionet.molbio.ageing Subject: Cancer Enzyme A Necrosis Inhibiter? Date: 31 Dec 1994 23:50:09 GMT Organization: Celsine Corporation Lines: 9 Message-ID: <3e4qnh$pdm@mississippi.iac.net> NNTP-Posting-Host: ip31.iac.net X-Newsreader: WinVN 0.92.6+ Geron Corporation, Menlo Park, California, have discovered that virtually all human tumors contain a unique enzyme that blocks the biological clocks of the tumor cells. What if a similar enzyme were introduced into normal human cells so that their DNA doesn't deteriorate when the normal cells divide? Wouldn't this be an immortal creature? And what would be the implications of such a discovery? From owner-ageing@net.bio.net Sun Jan 01 22:00:00 1995 Newsgroups: bionet.molbio.ageing Path: biosci!newshost.lanl.gov!news.ttu.edu!seas.smu.edu!convex!insosf1.infonet.net!news-feed-1.peachnet.edu!gatech!swrinde!ihnp4.ucsd.edu!library.ucla.edu!psgrain!charnel.ecst.csuchico.edu!csusac!csus.edu!netcom.com!luly From: luly@netcom.com (Robert Luly) Subject: Re: Cancer Enzyme A Necrosis Inhibiter? Message-ID: Organization: NETCOM On-line Communication Services (408 261-4700 guest) X-Newsreader: TIN [version 1.2 PL1] References: <3e4qnh$pdm@mississippi.iac.net> Date: Sun, 1 Jan 1995 00:58:35 GMT Lines: 16 John Thomas Renfro (ren@iac.net) wrote: : Geron Corporation, Menlo Park, California, have discovered that virtually : all human tumors contain a unique enzyme that blocks the biological : clocks of the tumor cells. : What if a similar enzyme were introduced into normal human cells so that : their DNA doesn't deteriorate when the normal cells divide? : Wouldn't this be an immortal creature? And what would be the implications : of such a discovery? I assume you are refering to telomeres and telomerase. My understanding is that telomeres insure the accuracy of DNA transcription so they do serve a purpose. Cancer dosn't care what it looks like it just wants to be imortal so it can fool around with the telomeres and not worry about the side effects. If we are careful we may be able to benifit from what we learn from cancer not just cure it. Lets hope so. From owner-ageing@net.bio.net Sun Jan 01 22:00:00 1995 Path: biosci!agate!howland.reston.ans.net!newsserver.jvnc.net!netnews.upenn.edu!cronkite.ocis.temple.edu!astro.ocis.temple.edu!gold From: gold@astro.ocis.temple.edu (Bert Gold) Newsgroups: bionet.molbio.ageing Subject: Hayflick's Book Date: 2 Jan 1995 16:34:15 GMT Organization: Temple University, Academic Computer Services Lines: 18 Message-ID: <3e99u7$8vn@cronkite.ocis.temple.edu> NNTP-Posting-Host: astro.ocis.temple.edu X-Newsreader: TIN [version 1.2 PL2] Netters: Have you read Leonard Hayflick's Book on "How and Why we Age" ? Are you interested in conversing about this book an attempt to provide a unified theory of current thinking on apoptosis and aging? Perhaps we can write some kind of minireview together... I would be interested in communicating with others thinking about this issue. Bert Gold From owner-ageing@net.bio.net Sun Jan 01 22:00:00 1995 Path: biosci!bloom-beacon.mit.edu!spool.mu.edu!uwm.edu!psuvax1!news.pop.psu.edu!news.cac.psu.edu!newsserver.jvnc.net!netnews.upenn.edu!cronkite.ocis.temple.edu!astro.ocis.temple.edu!gold From: gold@astro.ocis.temple.edu (Bert Gold) Newsgroups: bionet.molbio.ageing Subject: Apoptosis Revisited Date: 2 Jan 1995 16:40:52 GMT Organization: Temple University, Academic Computer Services Lines: 21 Message-ID: <3e9aak$8vn@cronkite.ocis.temple.edu> NNTP-Posting-Host: astro.ocis.temple.edu X-Newsreader: TIN [version 1.2 PL2] I am posting Richard Lockshin's response to my post because it is both informative and timely. Lockshin (rick@sjubiol.stjohns.edu) writes: > Several attempts have been made to clarify the point. See for instance, article by Zakeri and Lockshin, Ann. NY. Acad. Sci., : The Biological Clock... (1994) or Cope/Tomei book "Apoptosis" (Cold Spring Harbor). "programmed cell death" implies documentation of requirement for protein synthesis. "apoptosis" describes a morphology and potentially a mechanism of one of the most common types of controlled cell death. necrosis differs in that it is inherently uncontrolled and ends in osmotic lysis. Check out other major reviews on the subject, such as Ellis/Horvitz Ann Revs Cell Biol, etc. > Thank you for your response, Richard. Bert Gold From owner-ageing@net.bio.net Mon Jan 02 22:00:00 1995 Path: biosci!bloom-beacon.mit.edu!uhog.mit.edu!news.intercon.com!panix!jmm.dialup.access.net!morphy From: morphy@alumni.caltech.edu (Jones M. Murphy, Jr.) Newsgroups: bionet.molbio.ageing Subject: Re: Hayflick's Book Date: Tue, 3 Jan 1995 02:41:03 GMT Organization: We Are The World Lines: 306 Message-ID: References: <3e99u7$8vn@cronkite.ocis.temple.edu> NNTP-Posting-Host: 198.7.7.105 X-Newsreader: Trumpet for Windows [Version 1.0 Rev B final beta #1] In article <3e99u7$8vn@cronkite.ocis.temple.edu> gold@astro.ocis.temple.edu (Bert Gold) writes: >From: gold@astro.ocis.temple.edu (Bert Gold) >Subject: Hayflick's Book >Date: 2 Jan 1995 16:34:15 GMT >Netters: >Have you read Leonard Hayflick's Book on "How and Why we Age" ? >Are you interested in conversing about this book >an attempt to provide a unified theory of >current thinking on apoptosis and >aging? >Perhaps we can write some kind of minireview together... >I would be interested in communicating with others thinking about >this issue. >Bert Gold I posted this review in the sci-life-extension newsgroup: From: morphy@alumni.caltech.edu (Jones M. Murphy, Jr.) Subject: REVIEW:How And Why We Age, by Leonard Hayflick (Ballantine Books, 1994) Date: Wed, 5 Oct 1994 19:12:53 GMT Leonard Hayflick is a cell biologist specializing in aging--a biogerontologist, as he describes himself. He is co-discoverer of the Hayflick limit, which is the number of times cells from a particular kind of differentiated tissue divide before dying(0, for example, in the case of brain or muscle cells). The book is a detailed survey of aging in humans, covering demography, physiology, and psychology. It continues by describing various strategies aimed at slowing the aging process. The author appears to be quite skeptical of all strategies except caloric restriction. However, he feels it's an unacceptable sacrifice in terms of quality of life. The author also goes on to discuss the desirability of extending life. He appears to be much more interested in extending health, than extending life. His views are well thought out and provocative, although I disagree with him. I heartily recommend the book, despite the fact that it's really a detailed exposition of why we don't know what aging is! Jones By the way, the ISBN is 0-345-33918-5 Here's the scanned-in Table Of Contents, with apologies for any mispellings my scanner may have rendered. FOREWORD by Robert N. Butler, M.D...................................... Introduction...................... P A R T O N E: What Is Aging? 1. Defining Aging.................................. Chronological versus Biological Age 12 Longevity Aging, and Death Z5 How Old Are You-Really? 16 2. Some Animals Age, Some Do Not...... Animals That Do Not Age 21 Aging by Wear and Tear 23 Animals That Regenerate 24 "Big Bang" Reproduction and Aging 24 How Long Do Animals Live? 27 3. Redwood Trees Are Not Old......... Aging and Cell Lineages 35 Grafts and Aging 36 Roots, Shoots, and Aging 36 Programmed Aging 37 The Longevity of Seeds 39 4. Aging Is Not a Disease......... Normal Age Changes 44 Causes of Death 45 Age-related Illnesses 47 Population versus Individual Aging 48 PART TWO: Aging by The Numbers 6. The Demographic Facts of Life....... The Graying of America 54 The Statistics Today 57 The Statistics Tomorrow 59 Some Geographical Facts 59 fi. Actuarial Aging......................... The Likelihood of Death 64 Are We Living Longer? 66 How Many Years Are Left? 67 The Tables of Life 68 Life Tables for Animals 77 The Curves of Life 77 Rectangularizing the Survival Curve 83 Yes, We Are Living Longer 84 7. A Long and Healthy Life...-.. ...... What Is Your Active Life Expectation? 90 Extending Health and Compressing Illness ls Life Span Fixed Or Changing? 93 Do Some Occupations Favor Longevity? 94 What Will Happen When All Diseases Are Cured? 96 Why Do Women Live Longer than Men? 101 Is There a Weaker Sex? 104 Accelerated Aging in Humans 107 Why Are We Old at Age Sixty-Five? 108 PART THREE: How Do We Age? 8. Aging under Glass.................. Aging in a Bottle 112 An Old Dogma Dies 116 Transplanting Normal Cells 124 Aging Adult Cells 126 Accelerated Aging in a Bottle Carrel's Mistake 127 Life in the Cold 130 Cellular Memory 130 A Practical Use 131 Cell Aging and Cell Longevity 132 The Latent Period 136 9. The Baltimore Longitudinal Study of Aging................... Separating Facts from Myths 142 Changes in Appearance 143 Dental Changes 143 Weight and Metabolic Changes 143 Changes in the Cardiovascular System 144 Changes in Reaction Time 144 Cognitive Changes 144 Personality Changes 145 Changes in Sexual Activity 145 Changes in the Senses 146 Physiological Changes 146 Changes in Strength 147 Gender Differences in Aging 147 General Conclusions from the BLSA 148 10. How We Change with Age............................................... The Cardiovascular System 151 The Immune System 153 The Endocrine System 155 The Female Reproductive System 157 The Male Reproductive System 159 The Skeletal System 160 The Nervous System 161 The Brain 161 11. Aging from Head to Foot................................................. Height 166 Weight 167 Chest Size 168 Arm Span 168 Face 168 Skull 168 Skeleton 169 Body Composition Body Water 169 Skin 170 WRlNKLES . SWEAT GLANDS · TEMPERATURE CONTROL . HEALING CAPAClTY Fingernails 174 Hair 175 Hearing 176 Taste 177 Smell 178 Sight 179 Sleep 179 Nutrition 18l Metabolism 182 Capacity for Exercise 184 Chronic Diseases 185 Aging Has Its Compensations 185 PART FOUR: Why Do We Age? 12. Centenarians and Supercentenarians........................ Superlongevity throughout the Ages 190 LUIGI CORNARO AND THE SPARTAN LIFE . DESCARTES AND BACON . EARLY BLOOD TRANSFUSIONS . SUPERLONGEVOUS INDIVIDUALS . MODERN SKEPTICISM Are There Superlongevous People? 196 What about Centenarians? 202 The Increased Likelihood of Reaching Age One Hundred 2a Some Statistical Characteristics of Centenarians 206 13. Determining Life Span............................................... How Life Span Relates to Brain Weight and Body Weight 2 Body Temperature and Metabolic Rate 212 Lengthening Life Spans 213 Did Age Evolve? 215 The Importance of Redundancy 216 14. Theories of Aging Based on Purposeful Events..... Early Ideas About Aging 223 THE "VITAL SUBSTANCE" THEORY · THE GENETIC MUTATION THEORY . THE REPRODUCTIVE EXHAUSTION THEORY Why Modern Theories of Aging Are Still Speculative 226 Rules of the Game 228 Is Aging Accidental or Programmed? 229 Aging By Design 229 The Neuroendocrine Theory 231 Down the Brain-cell Drain 233 15. Theories of Aging Based on Random Events....... The Wear and Tear Theory 236 The Rate of Living Theory 239 The Waste Product Accumulation Theory 247 The Cross-linking Theory 242 The Free Radical Theory 244 The Immune System Theory 248 Theories of Errors and Repairs 250 The Order to Disorder Theory 257 Why Do We Age? 258 A Personal View 259 PART FIVE: Slowing Aging and Increasing Life Span 16. Early Attempts to Control Aging..... Should We Try to Cheat Death? 265 Should We to Control Aging? 267 Rejuvenating Substances 269 Alchemy 269 Cavorting 271 Scrotum Hokum and Other Nonsense 272 Cell Therapy 274 Yogurt 274 Sterilization 275 Procaine 276 17. How Exercise, Nutrition, and Weight Affect Longevity The Effect of Exercise on Aging and Life Span 278 The Longevity of College Athletes 280 The Longevity of Baseball Players 282 The Longevity of Old Athletes 282 Is There an Antiaging Diet? 283 How Does Caloric Restriction Work? 287 Can Humans Increase Their Longevity by Caloric Restriction? 289 Ideal Weight and Longevity 292 18. How Temperature, Light, Transfusions, and Suspended Animation Affect Longevity.............................................. Temperature and Aging 296 Suspended Animation 298 Cryonics 300 Aging in the Dark 301 Can Transfusions Affect Longevity? 302 19. The Clocks That Time Us.... ....... Our Perception of the Passage of Time 304 Circadian Rhythms 305 Where Is the Clock? 307 Aging Clocks 308 A Sure Way to Slow Aging 308 An Easy Way to Increase Your Longevity 310 PART SIX: The Future of Human Aging and Longevity zo. Life Extension and Antiaging Therapies........... Antiaging Therapies and Profits 314 How Do We Test What Cannot Be Measured? 31S What Would Happen if We Learned How to Manipulate Longevity? 315 At What Age Are We Most Productive? 316 21. Aging and Longevity in the Twenty-first Century.... The Effect of Genetics on Future Longevity 319 The Effect of Nurture on Future Longevity 321 Twenty-first-Century Demographics 322 Our Future Selves 325 Living the Rectangular Life 330 Can We Extend Our Life Span? 331 Research on Longevity and Aging Today 332 What Should Our Goals Be? 334 No More Aging: Blessing or Nightmare? 336 Immortality 338 The Population Bomb 339 How to Increase Life Expectation 341 From owner-ageing@net.bio.net Mon Jan 02 22:00:00 1995 Path: biosci!galaxy.ucr.edu!ihnp4.ucsd.edu!swrinde!cs.utexas.edu!howland.reston.ans.net!news.sprintlink.net!sun.cais.com!news.iac.net!news From: ren@iac.net (John Thomas Renfro) Newsgroups: bionet.molbio.ageing Subject: Collective Research Date: 3 Jan 1995 23:42:39 GMT Organization: Celsine Corporation Lines: 26 Message-ID: <3ecndf$99q@mississippi.iac.net> NNTP-Posting-Host: ip31.iac.net X-Newsreader: WinVN 0.92.6+ Ageing is a very complex process and indeed involves chemical and physiological death-mechanisms. But all of these mechanisms seem to be tied into the programming of the DNA. Further, specialized cells seem to die and reproduce at different rates. Skin cells die faster than brain cells, unless you were at my New Year's Eve Party. Tsk Tsk. If we could isolate this enzyme within cancer cells and re-design it to only interact with vital tissue and organs which maintain the awareness of the organism such as brain cells, then immortality could be possible. Further, if gene-therapy and mapping continues to advance at this rate, we could design a human-being with many interesting properties. How about someone who could regenerate flesh like the star-fish. The implications of creating a super-race has dark-overtones if used for martial gain. But if gene-gineering were handled with the goal of improving our lives, an immortal, resiliant race wouldn't be so bad. It has always been the goal of humanity to control pain and death. Don't you want to live forever? Nature's reason for the cycles of life and death are simple. ...to create a better tomatoE. But if humanity can learn to control the evolution of the human body through genetics, why would death be neccessary anymore? I would like to hear your opinion. From owner-ageing@net.bio.net Tue Jan 03 22:00:00 1995 Path: biosci!CS.Arizona.EDU!news.Arizona.EDU!hamblin.math.byu.edu!sol.ctr.columbia.edu!howland.reston.ans.net!pipex!sunsite.doc.ic.ac.uk!daresbury!not-for-mail From: draye@gena.ucl.ac.be (Xavier DRAYE) Newsgroups: bionet.molbio.ageing Subject: Re: Collective Research Date: 4 Jan 1995 08:44:46 -0000 Lines: 26 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <3edn5u$m31@mserv1.dl.ac.uk> X-Sender: draye@sci1.sri.ucl.ac.be Original-To: ageing@dl.ac.uk >The implications of creating a super-race has dark-overtones if used for >martial gain. But if gene-gineering were handled with the goal of >improving our lives, an immortal, resiliant race wouldn't be so bad. > >It has always been the goal of humanity to control pain and death. Don't >you want to live forever? > >Nature's reason for the cycles of life and death are simple. ...to create >a better tomatoE. But if humanity can learn to control the evolution of >the human body through genetics, why would death be neccessary anymore? > >I would like to hear your opinion. The first idea which comes to my mind is probably not so attractive... We are more than 6 10E9 peoples on the Earth, and it seems we could be faced soon with managing problems. Anyway, when you promise immortality, you should also promise a severe restriction *abolition?* of reproduction. This implies 1) that we be able to proceed to such a control, 2) that contraception becomes 100% efficient 3)... Xavier draye@gena.ucl.ac.be From owner-ageing@net.bio.net Tue Jan 03 22:00:00 1995 Path: biosci!newshost.lanl.gov!news.ttu.edu!seas.smu.edu!convex!insosf1.infonet.net!solaris.cc.vt.edu!swiss.ans.net!gatech!bloom-beacon.mit.edu!news.bu.edu!tholeva From: tholeva@bu.edu (Thomas Holeva) Newsgroups: bionet.molbio.ageing Subject: cholesterol Date: 4 Jan 1995 18:24:52 GMT Organization: Boston University Lines: 7 Message-ID: <3eep5k$85p@news.bu.edu> NNTP-Posting-Host: acs3.bu.edu X-Newsreader: TIN [version 1.2 PL0] Can anyone point me to some info on this supposed link between low cholesterol levels in the blood and an old age 'gene'. I heard something on this ahile back and am interested in knowing more. Thanks, Tom From owner-ageing@net.bio.net Tue Jan 03 22:00:00 1995 Newsgroups: bionet.molbio.ageing Path: biosci!daresbury!trane.uninett.no!eunet.no!nuug!EU.net!howland.reston.ans.net!ix.netcom.com!netcom.com!luly From: luly@netcom.com (Robert Luly) Subject: Re: hungry Message-ID: Organization: NETCOM On-line Communication Services (408 261-4700 guest) X-Newsreader: TIN [version 1.2 PL1] Date: Wed, 4 Jan 1995 22:07:49 GMT Lines: 14 There are a lot of people on earth, true but those who are crowded choose to be so. There is plenty of land left for people (and other animals too) without over crowding. I travel and I have seen this for myself. The only ones who want to stop all new births have allready been born, that's not very fair. It has been calculated that even if we eliminate all natural causes of death, we would live to an average age of 800 years before something gets you. I would not argue for unlimited births, but there would always be someone dieing to make room for more. From an evolutionary standpoint I think I can meke a good case for a longer life span due to the complexity of the world as we have made it. If good health could be maintained then you could remain a tax payer instead of a tax user.This is one way we could eliminate the national debt and with social security and medicade the 2 biggest liabilities for this country this may be the easiest solution. Think about it :) From owner-ageing@net.bio.net Tue Jan 03 22:00:00 1995 Newsgroups: bionet.molbio.ageing Path: biosci!daresbury!trane.uninett.no!eunet.no!nuug!EU.net!howland.reston.ans.net!ix.netcom.com!netcom.com!luly From: luly@netcom.com (Robert Luly) Subject: Re: cholesterol Message-ID: Organization: NETCOM On-line Communication Services (408 261-4700 guest) X-Newsreader: TIN [version 1.2 PL1] References: <3eep5k$85p@news.bu.edu> Date: Wed, 4 Jan 1995 22:28:44 GMT Lines: 11 Thomas Holeva (tholeva@bu.edu) wrote: : Can anyone point me to some info on this supposed link : between low cholesterol levels in the blood and an old age 'gene'. : I heard something on this ahile back and am interested in knowing more. : Thanks, : Tom The only thing I recall ( other than the usual "lower is better" but not associated with genes) is about higher HDL in some Itialian family being caused by a gene and this family all lived to a very old age. Look for Apo Milano. From owner-ageing@net.bio.net Wed Jan 04 22:00:00 1995 Path: biosci!PCLSP2.KUICR.KYOTO-U.AC.JP!vinz From: vinz@PCLSP2.KUICR.KYOTO-U.AC.JP (Vincenzo Nardi-Dei) Newsgroups: bionet.molbio.ageing Subject: Re: Collective Research Date: 4 Jan 1995 03:11:38 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 35 Sender: daemon@net.bio.net Distribution: world Message-ID: <9501041113.AA27932@pclsp2> >The implications of creating a super-race has dark-overtones if used for >martial gain. But if gene-gineering were handled with the goal of >improving our lives, an immortal, resiliant race wouldn't be so bad. > >It has always been the goal of humanity to control pain and death. Don't >you want to live forever? > >Nature's reason for the cycles of life and death are simple. ...to create >a better tomatoE. But if humanity can learn to control the evolution of >the human body through genetics, why would death be neccessary anymore? > >I would like to hear your opinion. To be immortal is not so attractive to me. Death close a cycle, and the nothing we will face after death is not a displeasure. But if you find a way to remain young and active untill death, I would be the first to subscribe... :-) :-) Also I don't believe that telomeres shortening and telomerase are the only responsabile for death, that has mechanisms much more complex, the prouve is that there is no reported mutants immortal between higher animals. It is meanwhile possible, that restoring telomerases efficiency would postpone for a while our death and keep us younger until then, if not other (that is very likely too) side effects appear. Anyway, an Happy New Year, and not to remind you that an other year of our life has passed... :-) Vincenzo From owner-ageing@net.bio.net Wed Jan 04 22:00:00 1995 Path: biosci!galaxy.ucr.edu!ihnp4.ucsd.edu!swrinde!cs.utexas.edu!uunet!winternet.com!technix!rosevax!incstar!adam.incstar.com!colford Newsgroups: bionet.molbio.ageing Subject: Re: Collective Research Message-ID: <1995Jan4.130906.1@adam.incstar.com> From: colford@adam.incstar.com Date: 4 Jan 95 13:09:06 CDT References: <3ecndf$99q@mississippi.iac.net> Nntp-Posting-Host: adam Nntp-Posting-User: colford Lines: 29 > > The implications of creating a super-race has dark-overtones if used for > martial gain. But if gene-gineering were handled with the goal of > improving our lives, an immortal, resiliant race wouldn't be so bad. > > It has always been the goal of humanity to control pain and death. Don't > you want to live forever? > > Nature's reason for the cycles of life and death are simple. ...to create > a better tomatoE. But if humanity can learn to control the evolution of > the human body through genetics, why would death be neccessary anymore? > > I would like to hear your opinion. We would have to tie new births strictly with accidental deaths to balance the population, assuming zero population growth is a good idea. when this immortality technology became available, I would suggest that the population of the earth would be such that zero population growth would not be a goal, but rather population reduction will be. Everything in life is a balancing act, and intelligent beings have the unfortunate ability to convince themselves they can hop in without capsizing the boat. Apart from any ethical consideration, in the imaginable future we will not be good enough to have a handle on the human body to change a fully grown adult into an immortal. From owner-ageing@net.bio.net Wed Jan 04 22:00:00 1995 Path: biosci!galaxy.ucr.edu!ihnp4.ucsd.edu!library.ucla.edu!agate!spool.mu.edu!olivea!uunet!psinntp!sjuvm!yprlbio Nntp-Posting-Host: 149.68.2.20 Date: Thu, 5 Jan 1995 09:54:23 -0500 From: "LOCKSHIN, RICHARD A" Newsgroups: bionet.molbio.ageing Subject: Re: Necrosis versus Apoptosis Message-ID: <05JAN95.10698103.0030@sjumusic.stjohns.edu> References: <9412291617.AA15897@pclsp2> Sender: usenet@sjumusic.stjohns.edu Organization: St. John's University Lines: 36 In article <9412291617.AA15897@pclsp2> vinz@PCLSP2.KUICR.KYOTO-U.AC.JP (Vincenzo Nardi-Dei) writes: >Gold wrote: > >>Hey, has anyone out there read "Ideas in Pathology, Programmed Cell Death: >>Necrosis versus Apoptosis" in Modern Pathology, Volume 7, pages 605-609 >>(1994). >> >>The gist of the article is that the term "apoptosis" adds to the confusion >>of the >>study of cell death, rather than clarifying it. And that the distinction >>between necrosis and apoptosis lacks clarity and is "confusing and ... >>unintelligible". >> >>Comments, netters... > >So how do they propose to define programmed cell death? > programmed cell death refers to the identification of a sequence of events, now presumed to be gene activity, that leads a cell to become irreversibly committed to death. See articles on original use of term (Lockshin and Williams, 1964-1965, J. Insect Physiology) or review by Saunders, Science, 1966, or any of several recent reviews (Lockshin, Zakeri & Lockshin, etc) in Ann Rev NY Acad Sci, FASEB J, Cold Spring Harbor Symp, elsewhere. Richard A. Lockshin/Dept. Biol. Sci. St. John's U.8000 Utopia Pkwy Jamaica NY 11439 USA/Phone 718: 990-1854/ Fax 718: 380-8543 >Vincenzo Nard-Dei > >Institute for Chemical Research >Kyoto University > > >. >. From owner-ageing@net.bio.net Wed Jan 04 22:00:00 1995 Path: biosci!bloom-beacon.mit.edu!uhog.mit.edu!nntp.club.cc.cmu.edu!newsfeed.pitt.edu!uunet!fonorola!inforamp.net!woody16.inforamp.net!intermed From: intermed@inforamp.net (Ian Clarke) Newsgroups: bionet.molbio.ageing Subject: Attention Canadian Researchers Date: Thu, 5 Jan 1995 12:53:16 Organization: InfoRamp Inc. Lines: 19 Message-ID: NNTP-Posting-Host: woody16.inforamp.net X-Newsreader: Trumpet for Windows [Version 1.0 Rev A] Inter Medico is the Canadian distributor for many of the world's leading molecular biology companies. Inter Medico represents Genzyme(cytokines, chemokines, cell adhesion molecules), Novagen (pET bacterial expression systems, mRNA purification systems), Amresco (fine chemicals, thermostable DNA polymerases, nucleic acid isolation kits), SLT (ELISA readers, fluorometers, microplate washers), BioDesign (a huge selection of biologically important antibodies), and The Binding Site ( clinically-relevant antibody-based diagnostic systems). As part of Inter Medico's continuing dedication to the Canadian research community, we have established a user-group to share the latest information about molecular biology products designed to save you time and money. There are valuable discounts available only to subscribers. There is no charge to join. If you are interested in joining, please send an e-mail message to Majordomo@inforamp.net. In the body of the letter, type Subscribe Research . Join today, and start enjoying the benefits immediately. From owner-ageing@net.bio.net Wed Jan 04 22:00:00 1995 Newsgroups: bionet.drosophila,bionet.general,bionet.genome.arabidopsis,bionet.genome.chrom22,bionet.genome.chromosomes,bionet.immunology,bionet.info-theory,bionet.jobs,bionet.journals.note,bionet.metabolic-reg,bionet.molbio.ageing,bionet.molbio.bio-matrix,bionet.molbio.embldatabank,bionet.molbio.evolution,bionet.molbio.gdb,bionet.molbio.genbank,bionet.molbio.gene-linkage,bionet.molbio.genome-program,bionet.molbio.hiv Path: biosci!bloom-beacon.mit.edu!gatech!newsfeed.pitt.edu!uunet!xnet!quake.xnet.com!research From: crta@xnet.com (Norman Fraley) Subject: New Research & Testing Association Formed Message-ID: Sender: news@amiserv.chi.il.us Nntp-Posting-Host: research.crta.org Organization: Contract Research & Testing Association X-Newsreader: News Xpress Version 1.0 Beta #2 Date: Thu, 5 Jan 1995 20:52:00 GMT Lines: 66 Xref: biosci bionet.drosophila:777 bionet.general:12714 bionet.genome.arabidopsis:2789 bionet.genome.chromosomes:390 bionet.immunology:2755 bionet.info-theory:3047 bionet.jobs:6983 bionet.journals.note:371 bionet.metabolic-reg:390 bionet.molbio.ageing:1085 bionet.molbio.bio-matrix:526 bionet.molbio.embldatabank:419 bionet.molbio.evolution:2265 bionet.molbio.gdb:273 bionet.molbio.genbank:1873 bionet.molbio.gene-linkage:506 bionet.molbio.genome-program:1101 bionet.molbio.hiv:814 As the primary resource of research information, the Internet was the primary choice for making all concerned individuals aware of the formation of the Contract Research & Testing Association. CRTA is an International Association designed to serve the needs of contract research, product and process development organizations and consultants throughout the world. Contract research organizations have specific public, governmental, and industry perception and promotion needs which are not addressed by existing scientific industry associations. CRTA operates as a non-profit, tax-exempt, corporation eligible for scientific research and public awareness charitable organization contributions as provided for in the IRC 501(c)(3) provisions. Being a scientific research and public awareness related organization, CRTA exists to benefit its members by providing: 1) An organization devoted to the promotion of Contract Research. 2) A unified voice on matters of common interest or concern. 3) Point of contact for media relations relative to contract research. 4) Business opportunity referrals as a research clearinghouse. 5) Professional networking opportunities for its members. 6) Periodic publishing of information beneficial to the membership. 7) Periodic dissemination of applicable research results to the public. 8) Governmental representation on issues affecting CRO's. 9) Public promotion of the strengths of its membership. 10) A directory of Contract Research Organizations and Consultants. CRTA will provide: 1) A forum for the exchange of information. 2) Formal recognition to the CRO's role in business. 3) Standards for the professionals so engaged. 4) Representation the profession in matters of common interest. 5) The development of techniques and methods to improve the practice and management of CROs. CRTA will also offer: 1) A monthly news publication. 2) Annual meetings 3) Active promotional media publicity programs. 4) A professional placement service 5) A Contract Research Service Directory. 6) Media topics and contacts directory If you have an interest in joining the Contract Research & Testing Association, please E-mail your reply to crta@xnet.com. Please include: 1) The word "membership" in your RE: or header information, 2) Your interest in the association / your area of work, 3) Your dues payment preference (check, money order, credit card, company check, wire xfer, etc.) DO NOT INCLUDE ANY CREDIT CARD INFORMATION! Only your preference for the manner of payment. 4) Most importantly, your email address, and additional contact information if you desire. We will then e-mail membership information and ALL FURTHER INFORMATION directly to you at your email location. Thank you for taking the time to read this announcement. If membership in this program this does not appeal to you, thank you for your patience and understanding. Sincerely, Membership Department Contract Research & Testing Association Best Regards, Norman Fraley CRTA@xnet.com Executive Director BBS:708-515-0494 Contract Research & Testing Association From owner-ageing@net.bio.net Thu Jan 05 22:00:00 1995 Newsgroups: bionet.molbio.ageing Path: biosci!daresbury!sunsite.doc.ic.ac.uk!agate!spool.mu.edu!caen!msunews!harbinger.cc.monash.edu.au!news.cs.su.oz.au!metro!psycho.biz.usyd.edu.au!scott From: scott@microsup14.ucc.su.oz.au (Scott A. Robson) Subject: Re: Cancer Enzyme A Necrosis Inhibiter? Message-ID: Sender: news@ucc.su.OZ.AU Nntp-Posting-Host: psycho.biz.usyd.edu.au Organization: Information Services, Sydney University, Sydney, NSW, Australia X-Newsreader: TIN [version 1.2 PL2] References: <3e4qnh$pdm@mississippi.iac.net> Date: Fri, 6 Jan 1995 09:25:43 GMT Lines: 25 John Thomas Renfro (ren@iac.net) wrote: : Geron Corporation, Menlo Park, California, have discovered that virtually : all human tumors contain a unique enzyme that blocks the biological : clocks of the tumor cells. : What if a similar enzyme were introduced into normal human cells so that : their DNA doesn't deteriorate when the normal cells divide? : Wouldn't this be an immortal creature? And what would be the implications : of such a discovery? I think you are refering to telomerase (sp?) which ensures that the telomeres of the DNA do not shorten with each division. Thus, the cells can divide indefinently. The problem of inserting this gene into old cells would be the potential of creating cancer in these cells. It would be a delecate and thin fence you would be walking on. Still, research could be interesting As for the implications, hmmm, very interesting, perhaps we can discuss this in about 200 yrs time :) Perosnally I'd like to live this long, so long as I was still healthy -- Scott A. Robson is scott@psycho.biz.usyd.edu.au better known as Krust-E From owner-ageing@net.bio.net Sat Jan 07 22:00:00 1995 Message-ID: <024338Z08011995@anon.penet.fi> Path: biosci!bloom-beacon.mit.edu!gatech!swrinde!pipex!sunic!news.funet.fi!news.eunet.fi!anon.penet.fi Newsgroups: bionet.general,bionet.molbio.ageing From: an98497@anon.penet.fi X-Anonymously-To: bionet.general,bionet.molbio.ageing Organization: Anonymous contact service Reply-To: an98497@anon.penet.fi Date: Sun, 8 Jan 1995 02:42:49 UTC Subject: Hair Growth Linked To Growth Hormone? Lines: 178 Xref: biosci bionet.general:12747 bionet.molbio.ageing:1087 I think this may be true, based on my own experience. In 1990, at the age of 32, I was losing my hair really fast, and spent a small fortune (almost $3,000) for one of those elaborate hair "systems." It was a real pain, and costed $100 a month to maintain. Being a believer in good nutrition my entire life, and having read about the effects of growth hormone, I couldn't help wondering if my hair loss at an early age was linked to my body having a growth hormone deficiency. I read that after the age of 30, your body gradually decreases production of the substance by its pituitary gland. I also heard that a healthy level of growth hormone in the body, helps keep the testosterone balance in check (something believed accountable for hair loss). Also, I heard that catching hair loss at an early age as I did (at age 32), gives a better chance of recovery (i.e., they even mentioned that regarding monoxodil (sp) that you apply to the scalp to stimulate blood circulation and hair growth, which I personally think is too risky considering that this is really a form of high blood pressure medicine, I read somewhere). About that time, I started reading about how pharmaceutical grade amino acids (which are available in health food stores), such as L-2 Amino-5 Guanidopentanoic Acid, L 2.5 Diaminopentoic Acid Monohydrochloride HCI, D 2 Amino 3 Hydroxybutric Acid, taken in combination with Pyridoxine HCI, can stimulate the pituitary gland into increased production of growth hormone NATURALLY OCCURRING IN THE HUMAN BODY. In other words, when you're a teenager and young adult, your body's pituitary gland naturally produces a lot of precious growth hormone, pumping it through the bloodstream. Yet for some reason, after the age of 30, the body's production of growth hormone diminishes. However, taking the above pharmaceutical grade amino acids, and combining this with a nutritious diet and rest (to nourish the pituitary gland which is stimulated to work harder by the amino acids), growth hormone production is often increased to pre-30 levels. I decided to look into sources of pharmaceutical grade amino acids, and discovered a company in San Mateo, California, owned by a bio-tech inventor who has developed a proprietary method of amino formulation in his lab. After spending thousands of dollars on real human hair (woven to my own hair, a rather painful process that pulls the scalp as the hair is braided), I figured that I had nothing to lose. I calculated that my lifetime expenditure from the hair "system" alone (maintenance and new "systems" as my old hair wore out), would put my retirement in jeopardy. For example, at $3,000 every 2 years and $100 a month, I would spend $66,000 making that hair tycoon rich over the next 30 years (and that's not calculating the interest and inflation factors)! Imagine multiplying $66,000 times all the people who get these hair "systems"! Wow. So I decided to try the proprietary amino acid formulation by this bio-tech inventor, after seeing my friends (in their 40's) go through another type of transformation that results from increased hormone production -- elastic skin that lacks wrinkles and the pallor of aging. They looked really bad before taking the amino's for a year from this inventor's company (if you're reading this, no offense!). After a year of taking this particular pharmaceutical grade amino formulation containing amino's such as L-2 Amino-5 Guanidopentanoic Acid, L 2.5 Diaminopentoic Acid Monohydrochloride HCI, and D 2 Amino 3 Hydroxybutric Acid in combination with Pyridoxine HCI, my friends looked really great. The "crows feet" were disappearing, and although they caught their hair loss apparently too late (as their hair didn't grow back, as mine later did starting at the age of 33), the rest of them looked pretty darned good for being in their 40's and having lived a life consisting of poor eating and sleeping habits. (Again, if you're reading this, no offense, you look great now!) I'm sure they'll recognize I'm talking about their experience, but it's impacted me so much that I wanted to share it on the net, along with my own experience. Anyway, I started taking these amino acids from this company, back in 1990 shortly after I spent all that money for a "new" head of hair (to use a worn-out cliche). As I said, I figured that I had nothing to lose, since if I didn't do something, I'd spend my retirement funds that should be invested, on hair. Besides, I compared the cost on a per gram basis, to other similar amino acids at my health food store, and shopped around, and the price per gram was pretty much the same. A bottle of gel caps (or a month's supply of it) contains a little over 100 grams (or I calculated, 102,000 milligrams or "mg"), of the above pharmaceutical grade amino's. The daily dosage, in other words, is 3.4 grams (or 3,400 mg). Within a year, I needed my hair "system" serviced more often. My hair was growing faster, which they attributed at first to the cold weather.(?) At first, I thought that the cold was making my hair grow fast, but it was growing really fast. Also, I seemed to heal faster from cuts, chapped lips, and my fingernails started growing faster (I had to clip them twice as often, it seemed). Also, being a stressed out computer "nerd," I was getting the beginnings of "crows feet" and my skin was a little stressed looking. This disappeared and my skin looked really good for once. I also caught the flu less often, missing the flu season. I felt really immune to things, as if my immunity was really boosted by the increased growth hormone levels evidently stimulated by these amino acids. Now I want to mention that I'm a non-smoker (never smoked), never used drugs of any kind, and since the age of 17 have always been into nutrition, good eating and sleeping habits, exercise, an overall healthy lifestyle. In spite of all this, the stress of making "ends meet" really was taking its toll, in my premature hair loss and prematurely aging skin appearance. All this started to noticeably change over the first year of taking these amino's before bedtime. By the way, I found through research that taking amino's BEFORE BEDTIME, is the best way for them to work, since the pituitary gland (which manufactures natural growth hormone in the human body), is most active during REM sleep, so that's the best time for the amino's to be circulating through the blood stimulating the pituitary gland. I take 3.4 grams (or 3,400 mg) before going to sleep. After almost 3 years of taking 3.4 grams per night on a steady basis, without interruption, they found it almost impossible to keep the "real" human hair weave mounted on my head. It was more like a very expensive baseball cap that kept coming loose, it was terrible. I kept wondering, why am I spending $100 a month on this? Also, it was starting to wear out, and they were offering me a "special" price on a new hair "system" (still over $2,000). Although convinced that removing it would mean being bald, I just couldn't see spending more money. So I had them remove it. Also, I figured that I had to choose between spending $100 a month for the hair, or roughly $40 a month for the amino acids. I couldn't afford both, as the recession had really kicked in, and was sinking my consulting business fast. So, would I spend roughly $40 a month putting just over 100 grams of potentially growth hormone stimulating amino acids into my body, or would I spend two and a half times that amount, braiding real human hair onto my own diminishing hair? The choice was obvious. A gamble, no doubt, but it turned out to payoff beyond my expectations. When she took the scissors and cut it off (and unraveled the braid), before I had a chance to look in the mirror, she asked me why I had it in the first place? That I could have done just fine without it! When I looked in the mirror, all my hair was back. It was a strange feeling. I told her that originally, I hardly had any hair on top of my head, but she humored me. I could tell she didn't believe that in 3 years of going there, it could have grown back. I mean, these sort of things don't happen in the "real world." (--grin!!!--) Although it was still a little limp and frizzy, it was all back and full length. What a relief. Now I didn't have to worry about not being presentable at a business presentation. Now it's been 5 years since I've taken these amino's, and my hair is thick and normal looking, and getting more bushy every few months. Every time I seem to enter a "growth spurt," as I call it (when I theorize that my body produces a rush of growth hormone), my scalp itches and a few weeks later, my hair looks more filled out. At the age of 37, people tell me that I look in my late 20's or early 30's. I was once even asked for ID, when I went out with some friends and wearing a leather bomber jacket (which combined with my looks, made me look a little too young for comfort). It was embarrassing and great. My skin looks so smooth, sometimes I stare in the mirror, it seems dreamlike. Well, I've gone on and on. I just wanted to share this experience on the net. I order my monthly supply by calling the bio-tech company's toll-free line, 800 - YOUTH-01. They are great too, in that they're willing to send out free literature on scientific studies and full information on it, so it's a real education just to read the free scientific literature and results of studies on people who take it. I'm impressed with the amount of research that went into it, as well as reports that many Hollywood celebrities are taking it and obviously benefiting from the skin growth aspects. Growth hormone therapy, is also being used successfully on AIDS patients, so it seems to me that stimulating a NATURAL RESPONSE would be preferable to artificial means, if possible. If growth hormone can do that to AIDS sufferers, then it seems to me that a healthy person can develop a super immune system. With all the plagues coming out of the ecologically damaged rain forests, a super immune system may be the ticket to survival. I've got to close, I got carried away here, and want to post this to a few places. I hope this experience has helped those who are looking for a natural way to use their own body's growth hormone producing capabilities, to heal the negative effects of oxidation and cellular breakdown caused by aging. By the way, the inventor of this formula is a researcher in aging, and has a wealth of valuable ideas. If you do decide to call the above toll free number (800 / YOUTH-01), perhaps suggest they get a WWW home page so people can learn more about the aging process, and the benefits of naturally produced human growth hormone. I think if enough people suggest this, this bio-tech company may decide it's worth getting a home page. I know this formula has helped a lot of sick people in my area, and as a healthy person, it's made me even better. I just hope more people can learn about it. ------------------------------------------------------------------------- To find out more about the anon service, send mail to help@anon.penet.fi. Due to the double-blind, any mail replies to this message will be anonymized, and an anonymous id will be allocated automatically. You have been warned. Please report any problems, inappropriate use etc. to admin@anon.penet.fi. From owner-ageing@net.bio.net Sun Jan 08 22:00:00 1995 Path: biosci!bloom-beacon.mit.edu!gatech!howland.reston.ans.net!ix.netcom.com!netnews From: monitor@ix.netcom.com (Mark Maupin) Newsgroups: bionet.general,bionet.molbio.ageing Subject: Re: Hair Growth Linked To Growth Hormone? Date: 9 Jan 1995 06:20:53 GMT Organization: Netcom Lines: 6 Distribution: world Message-ID: <3eqkk5$sjr@ixnews3.ix.netcom.com> References: <024338Z08011995@anon.penet.fi> NNTP-Posting-Host: ix-lb1-03.ix.netcom.com Xref: biosci bionet.general:12756 bionet.molbio.ageing:1088 In <024338Z08011995@anon.penet.fi> an98497@anon.penet.fi writes: > > >This is a test From owner-ageing@net.bio.net Tue Jan 10 22:00:00 1995 Path: biosci!POSSUM.MURDOCH.EDU.AU!cummins From: cummins@POSSUM.MURDOCH.EDU.AU (Dr Jim Cummins) Newsgroups: bionet.molbio.ageing Subject: Review of ageing Date: 10 Jan 1995 21:00:24 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 27 Sender: daemon@net.bio.net Distribution: world Message-ID: NNTP-Posting-Host: net.bio.net The Economist (January 7 1995: pp 68-70) has a nice review of current ageing research. It covers the evolutionary arguments for ageing and a "disposable soma"; artificial alterations of lifespan in Drosophila and C. elegans; free radicals and mitochondrial energetics; the Hayflick limit and telomerase; progeria and Werner's syndrome, and genetic markers of longevity. Appparently there's a company called Geron based in Menlo Park that is concentrating on life extending strategies by switching on telomerase in somatic cells. Anybody have any further information? Yours, virtually:- Jim "Spermatology rules o~ o~ o~ o~" Cummins Associate Professor in Veterinary Anatomy Murdoch University, Murdoch Western Australia 6150 Tel +61-9-360 2668 Fax +61-9-310 4144 E mail cummins@possum.murdoch.edu.au "Ignorance is a renewable resource" PJ O'Rourke. From owner-ageing@net.bio.net Tue Jan 10 22:00:00 1995 Path: biosci!BIOBASE.DK!thorup From: thorup@BIOBASE.DK (Jan Ulrik Thorup) Newsgroups: bionet.molbio.ageing Subject: How do cells count ?! Date: 11 Jan 1995 02:06:29 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 21 Sender: daemon@net.bio.net Distribution: world Message-ID: NNTP-Posting-Host: net.bio.net Dear netters. As far as I've understood, normal tissue cells divide a determined number of times (64 or so) and then they die. Cancer cells and neoplastic cell-lines seem to have lost this "limitation of number of divisions" and could in theory divide indefinitely. So how do normal cells count the number of divisions they have been through ? Do they accumulate a "count-protein" that increases in amount/cell with increasing division-passage, modify some other (more or less) vital part of the cells machinery (allow DNA to be mutated, allow oxidation, allow free radicals ...) slowly as they grow older or is there some other mechanism. What is known about cells "counting" today ? And might that "counting-meter" be reset to zero or at least be halted ? Sincerely, Jan E-mail thorup@biobase.dk From owner-ageing@net.bio.net Tue Jan 10 22:00:00 1995 Path: biosci!newshost.lanl.gov!news.ttu.edu!aurora.LaTech.edu!darwin.sura.net!spool.mu.edu!howland.reston.ans.net!news.sprintlink.net!redstone.interpath.net!hilbert.dnai.com!hack.dragoman.com!xdcrlab.com!user From: xdcrlab@quake.net (Mike Davis) Newsgroups: bionet.general,bionet.molbio.ageing Subject: Re: Hair Growth Linked To Growth Hormone? Date: 11 Jan 1995 16:15:57 GMT Organization: XdcrLab Lines: 16 Message-ID: References: <024338Z08011995@anon.penet.fi> NNTP-Posting-Host: xdcrlab.com X-Newsreader: Value-Added NewsWatcher 2.0b22.0+ Xref: biosci bionet.general:12810 bionet.molbio.ageing:1091 In article <024338Z08011995@anon.penet.fi>, an98497@anon.penet.fi wrote: > About that time, I started reading about how pharmaceutical grade amino > acids (which are available in health food stores), such as L-2 Amino-5 > Guanidopentanoic Acid, L 2.5 Diaminopentoic Acid Monohydrochloride HCI, D > 2 Amino 3 Hydroxybutric Acid, Don't be fooled, these are just arginine, ornithine and threonine. And GH has little to do with hair regrowth; although NO, nitric oxide, whose production is relateed to these aminos is linked to MPB. -- Mike Davis xdcrlab@quake.net "The stupid opinions expressed here are my own and should not be construed as superior to the stupid opinions of others. EITA" "Innovation is not dead it is merely being sat on" M.D. "You can't order inspiration" L. Riggle Davis From owner-ageing@net.bio.net Tue Jan 10 22:00:00 1995 Path: biosci!bcm!cs.utexas.edu!convex!convex!hermes.oc.com!hpsccs.oc.com!hoss From: hoss@hpsccs.oc.com (Chris Hoss) Newsgroups: bionet.molbio.ageing Subject: LITHIUM and ALZHEIMER's Disease Date: 11 Jan 1995 18:15:46 GMT Organization: OpenConnect Systems, Dallas, TX, USA Lines: 21 Message-ID: <3f178i$gtf@hermes.oc.com> NNTP-Posting-Host: hpsccs.mitek.com Has there been research in this area? This may be very helpful with the Alzheimer's disease. I know someone who has been on Lithium for over 15 years, and his memory is much better than mine. He can go back over 30 years and tell me very detailed information. And it makes sense, too, as LITHIUM is a salt that helps neutrons in the brain 'fire' electrically. Little is known and it is used for treatment of the 'bipolar' or 'maniac depressive' disorder. But helping the neutrons in the brain fire better may help overcome the blocking effect of the chemical that 'creates the forgetfulness' of alzheimer's disease. Maybe someone should investigate if there is any potential benefits. I know that there is work on isolating the chemical cause of Alzheimer's and then working on a cure. Just my two cents worth. Christopher Michael Hoss OpenConnect Systems, Inc From owner-ageing@net.bio.net Tue Jan 10 22:00:00 1995 Path: biosci!NETCOM.COM!wick From: wick@NETCOM.COM (Potter Wickware) Newsgroups: bionet.molbio.ageing Subject: Re: Review of ageing Date: 11 Jan 1995 12:44:01 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 54 Sender: daemon@net.bio.net Distribution: world Message-ID: References: NNTP-Posting-Host: net.bio.net I just this morning went to a presentation by Geron. They are not a true company in that they don't have a product, and are not close to having one. Nevertheless, they think they are on to something with telomerase and telomerase inhibition and believe they can appeal to the financial community for support even at this erly stage. Their principal focus is inhibiting the abnormal activity of the enzyme in tumor cells as a general therapy for several types of cancers. The premise is that suppressing telomerase would allow cancer cells to die a natural death, instead of proliferating endlessly. They say they have cloned the RNA portion of this enzyme complex; the protein portion remains elusive. A more distant goal of the company is to modulate the shortening of telomeres and thus extend replicative potential of cells thus targeted. The focus would be in striatum cells, for example, to prevent the premature death of brain cells in Parkinson's disease. Other degenerative diseases, too. Their chief scientist is Calvin Harley, from McMaster University (on leave). A paper of his was in the Dec 23 94 Science (Kan et al, Specific association of human telomerase activity with immortal cells and cancer.) Potter Wickware On 10 Jan 1995, Dr Jim Cummins wrote: > The Economist (January 7 1995: pp 68-70) has a nice review of current > ageing research. It covers the evolutionary arguments for ageing and a > "disposable soma"; artificial alterations of lifespan in Drosophila and C. > elegans; free radicals and mitochondrial energetics; the Hayflick limit and > telomerase; progeria and Werner's syndrome, and genetic markers of > longevity. > > Appparently there's a company called Geron based in Menlo Park that is > concentrating on life extending strategies by switching on telomerase in > somatic cells. Anybody have any further information? > > Yours, virtually:- > > Jim "Spermatology rules o~ o~ o~ o~" Cummins > > Associate Professor in Veterinary Anatomy > Murdoch University, > Murdoch Western Australia 6150 > Tel +61-9-360 2668 > Fax +61-9-310 4144 > E mail cummins@possum.murdoch.edu.au > > "Ignorance is a renewable resource" PJ O'Rourke. > > > > > > From owner-ageing@net.bio.net Tue Jan 10 22:00:00 1995 Path: biosci!bcm!cs.utexas.edu!howland.reston.ans.net!swiss.ans.net!prodigy.com!usenet From: RCCP51A@prodigy.com (Jim Dreher) Newsgroups: bionet.molbio.ageing Subject: Re: Hair Growth Linked To Growth Hormone? Date: 11 Jan 1995 20:38:42 GMT Organization: Prodigy Services Company 1-800-PRODIGY Lines: 7 Distribution: world Message-ID: <3f1fki$7gi@usenetw1.news.prodigy.com> NNTP-Posting-Host: inugap4.news.prodigy.com X-Newsreader: Version 1.2 A question for Mike Davis, Pardon my ignorance, but what is MPB ? Jim Jr From owner-ageing@net.bio.net Wed Jan 11 22:00:00 1995 Path: biosci!newshost.lanl.gov!news.ttu.edu!aurora.LaTech.edu!darwin.sura.net!gatech!howland.reston.ans.net!pipex!sunic!isgate!news.rhi.hi.is!sev From: sev@rhi.hi.is (Sigurdur Einar Vilhelmsson) Newsgroups: bionet.molbio.ageing Subject: Re: How do cells count ?! Date: 12 Jan 1995 11:14:43 GMT Organization: University of Iceland Lines: 39 Message-ID: <3f32v3$bkr@eldborg.rhi.hi.is> References: NNTP-Posting-Host: hengill.rhi.hi.is Mime-Version: 1.0 Content-Type: text/plain; charset=iso-8859-1 Content-Transfer-Encoding: 8bit In thorup@BIOBASE.DK (Jan Ulrik Thorup) writes: >Dear netters. As far as I've understood, normal tissue cells divide a >determined number of times (64 or so) and then they die. Cancer cells >and neoplastic cell-lines seem to have lost this "limitation of number of >divisions" and could in theory divide indefinitely. So how do normal >cells count the number of divisions they have been through ? Do they >accumulate a "count-protein" that increases in amount/cell with >increasing division-passage, modify some other (more or less) vital part >of the cells machinery (allow DNA to be mutated, allow oxidation, allow >free radicals ...) slowly as they grow older or is there some other >mechanism. What is known about cells "counting" today ? And might that >"counting-meter" be reset to zero or at least be halted ? >Sincerely, >Jan >E-mail thorup@biobase.dk Hi there Jan. One theory on division counting in cells is connected to the telomers, the ends of the chromosomes. This theory was put forward by, I think, Jerry Shay and others, but I donīt have the references at hand. The chromosome ends are packed in heterochromatin, but as the cell divides the ends shorten. This is due to the polymerases inability to replicate the DNA on the extreme ends. Studies have shown that as the chromosomes shorten, the heterochromatin moves inwards and the theory is that this affects genes positioned close to the telomers. When the heterochromatin moves into the control, or coding regions of these genes, they are blocked and the cell stops dividing. This is, in very short, one theory of how the cells can count their divisions. This is all from memory, but if you want me to refresh it, or give you references, please do not hesitate to let me know. Sigurdur E. Vilhelmsson sev@rhi.hi.is From owner-ageing@net.bio.net Wed Jan 11 22:00:00 1995 Path: biosci!PCLSP2.KUICR.KYOTO-U.AC.JP!vinz From: vinz@PCLSP2.KUICR.KYOTO-U.AC.JP (Vincenzo Nardi-Dei) Newsgroups: bionet.molbio.ageing Subject: Re: Telomerase kills! Date: 11 Jan 1995 18:53:19 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 21 Sender: daemon@net.bio.net Distribution: world Message-ID: <9501120254.AA00735@pclsp2> NNTP-Posting-Host: net.bio.net >This is just to kick up a controversy:- > >Telomerase stabilizes Cancer cells. Cancer works against normal cells. >Therefore the body is trying to get rid of telomerase and is deleting >the ends of chromosomes as a natural defence. Rather than claiming that >telomerase stabilizes the sperm cells, could it be that the sperm cells >nable to delete the ends of chromosomes? The telomerase thus produced >in sperm cells are transported to other cells in the human system and >cancer cells tend to get stabilized. This is easily verified by looking >up in infants if telomerase gene is active. .......................................................................... >S.Baranidharan Quite bizarre interpretation! Vincenzo From owner-ageing@net.bio.net Wed Jan 11 22:00:00 1995 Path: biosci!rutgers!gatech!europa.eng.gtefsd.com!news.umbc.edu!haven.umd.edu!purdue!mozo.cc.purdue.edu!not-for-mail From: barani@mace.cc.purdue.edu (Barani) Newsgroups: bionet.molbio.ageing Subject: Telomerase kills! Date: 11 Jan 1995 20:44:56 -0500 Organization: Purdue University Lines: 20 Message-ID: <3f21io$97f@mace.cc.purdue.edu> NNTP-Posting-Host: mace.cc.purdue.edu This is just to kick up a controversy:- Telomerase stabilizes Cancer cells. Cancer works against normal cells. Therefore the body is trying to get rid of telomerase and is deleting the ends of chromosomes as a natural defence. Rather than claiming that telomerase stabilizes the sperm cells, could it be that the sperm cells unable to delete the ends of chromosomes? The telomerase thus produced in sperm cells are transported to other cells in the human system and cancer cells tend to get stabilized. This is easily verified by looking up in infants if telomerase gene is active. o/~ o/~ o/~ ole ole ! Spermatology Kills! ole ole! o/~ o/` o/~ S.Baranidharan B-146, Lilly Hall of Life Sciences Purdue University W.Lafayette IN 47907-1392 USA. From owner-ageing@net.bio.net Wed Jan 11 22:00:00 1995 Newsgroups: bionet.molbio.ageing Path: biosci!rutgers!uwm.edu!vixen.cso.uiuc.edu!howland.reston.ans.net!ix.netcom.com!netcom.com!jimwork From: jimwork@netcom.com (James A. Work) Subject: Re: cholestrol Message-ID: Organization: NETCOM On-line Communication Services (408 261-4700 guest) X-Newsreader: TIN [version 1.2 PL1] Date: Thu, 12 Jan 1995 02:30:04 GMT Lines: 5 I don't know about the theory "The lower the better." Some types of cancers have LDL binding sites on their surfaces. A sudden drop in LDL might be bad news. -- James A. Work a major skew. jimwork@netcom.com From owner-ageing@net.bio.net Wed Jan 11 22:00:00 1995 Path: biosci!POSSUM.MURDOCH.EDU.AU!cummins From: cummins@POSSUM.MURDOCH.EDU.AU (Dr Jim Cummins) Newsgroups: bionet.molbio.ageing Subject: Re: Telomerase kills! Date: 11 Jan 1995 20:32:12 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 39 Sender: daemon@net.bio.net Distribution: world Message-ID: NNTP-Posting-Host: net.bio.net tbarani@mace.cc.purdue.edu (Barani) wrote:- > This is just to kick up a controversy:- > > Telomerase stabilizes Cancer cells. Cancer works against normal cells. > Therefore the body is trying to get rid of telomerase and is deleting > the ends of chromosomes as a natural defence. Rather than claiming that > telomerase stabilizes the sperm cells, could it be that the sperm cells > unable to delete the ends of chromosomes? The telomerase thus produced > in sperm cells are transported to other cells in the human system and > cancer cells tend to get stabilized. This is easily verified by looking > up in infants if telomerase gene is active. > > o/~ o/~ o/~ ole ole ! Spermatology Kills! ole ole! o/~ o/` o/~ Nice one ! :-) Problem is, I guess that the mature sperm cell probably does not contain telomerase, as this was used during spermatogenesis about 2-4 weeks before ejaculation. In addition the copy number (if present) would be far too low to affect all cells inthe system. Still, there are those reports of cervical cancer and its relationship with frequency of intercourse ........ No, Barani, I suggest you are really marching to the "feminazi" tune in attempting to demonise the innocent little genetic tadpoles ;-) Yours, virtually:- Jim "Spermatology rules STILL o~ o~ o~ o~" Cummins Associate Professor in Veterinary Anatomy Murdoch University, Murdoch Western Australia 6150 Tel +61-9-360 2668 Fax +61-9-310 4144 E mail cummins@possum.murdoch.edu.au "I hate quotations" From owner-ageing@net.bio.net Wed Jan 11 22:00:00 1995 Newsgroups: bionet.molbio.ageing Path: biosci!bcm!cs.utexas.edu!uunet!world!chi From: chi@world.std.com (Cambridge Healthtech Institute) Subject: Treatment of Osteoporosis Meeting Message-ID: Keywords: osteoporisis bone ageing Organization: Cambridge Healthtech Institute X-Newsreader: TIN [version 1.2 PL2] Date: Thu, 12 Jan 1995 19:12:43 GMT Lines: 17 Cambridge Healthtech Institute is organizing a meeting entitled, "Treatment of Osteoporosis," to be held May 22-23, 1995, in Philadelphia, PA. For registration information, information on presenting posters, or general inquiries, contact Cambridge Healthtech Institute: chi@world.std.com. *********************************************************************** *>>>>>>>>>>>> Cambridge Healthtech Institute <<<<<<<<<<<<<* *>>>>> 1000 Winter Street, Suite 3700 <<<<<* *~~~~~~~~~~~~~~~~~ Waltham, MA 02154 ~~~~~~~~~~~~~~~~~* *tel: 617.487.7989 fax: 617.487.7937* *e-mail chi@world.std.com ++++++++ ftp: ftp.std.com: /pub/chi* *>>>>>>>>>>>>World Wide Web: http://id.wing.net/~chi/homepg.html<<<<<<* *********************************************************************** From owner-ageing@net.bio.net Wed Jan 11 22:00:00 1995 Newsgroups: bionet.molbio.ageing Path: biosci!bcm!cs.utexas.edu!howland.reston.ans.net!ix.netcom.com!netcom.com!luly From: luly@netcom.com (Robert Luly) Subject: Re: cholestrol Message-ID: Organization: NETCOM On-line Communication Services (408 261-4700 guest) X-Newsreader: TIN [version 1.2 PL1] References: Date: Thu, 12 Jan 1995 19:31:17 GMT Lines: 10 James A. Work (jimwork@netcom.com) wrote: : I don't know about the theory "The lower the better." Some types of : cancers have LDL binding sites on their surfaces. A sudden drop in LDL : might be bad news. : -- : James A. Work a major skew. jimwork@netcom.com Yeah but....do those binding sites have enough total area to make a difference? I think that low LDL is a symptom not a cause but if I saw a *sudden* drop in LDL I think I would check under the hood just in case. I still think slowly lowering total cholestrol (except HDL) is better. From owner-ageing@net.bio.net Wed Jan 11 22:00:00 1995 Newsgroups: bionet.molbio.ageing Path: biosci!bcm!cs.utexas.edu!howland.reston.ans.net!ix.netcom.com!netcom.com!jimwork From: jimwork@netcom.com (James A. Work) Subject: Re: cholesterol Message-ID: Organization: NETCOM On-line Communication Services (408 261-4700 guest) X-Newsreader: TIN [version 1.2 PL1] Date: Thu, 12 Jan 1995 19:46:13 GMT Lines: 5 My aunt, who was a biochemist, religiously tracked her cholesterol. About six months ago, she died of squamous cell carcinoma, and her TC was down to 120 six months before her death. -- James A. Work a major skew. jimwork@netcom.com From owner-ageing@net.bio.net Thu Jan 12 22:00:00 1995 Path: biosci!bloom-beacon.mit.edu!satisfied.elf.com!news2.near.net!news.delphi.com!usenet From: jarice@delphi.com Newsgroups: bionet.molbio.ageing Subject: Alzheimer's Disease: A Treatment Strategy Date: Fri, 13 Jan 95 03:04:11 -0500 Organization: Delphi (info@delphi.com email, 800-695-4005 voice) Lines: 553 Message-ID: NNTP-Posting-Host: bos1d.delphi.com Magnesium "Oxidative stress and neurodegenerative processes are accompanied by a pronounced magnesium deficiency. This is also true for diseases associated with premature aging such as Down syndrome." (23) "Magnesium deficiency affects calcium transport and iron sequestration, impairs mitochondrial function, and induces radical generation by redox recycling. In contrast, magnesium administration improves energy and glucose utilization, stablizes enzymes and membranes, and protects biomolecules against oxidative damage by reactive radicals. It has been demonstrated that magnesium exhibits potent chemo- and cardio-protective actions. Newly developed magnesium salts, with greatly enhanced oral bioavailability and exhibiting extremely low toxicity, have been used sucessfully to counteract stress and age-related excitotoxicity in experiments in animals and humans. The administration of magnesium salts with high bioavailability (magnesium chloride [Slo-Mag], magnesium citrate [Citroma], magnesium hydroxide [Mag-Ox], magnesium pidolate) [22]prolongs life span and reverses age-related morphological, biochemical, electrophysiological, and behavioral impairments." (23) "The three major molecular mechanisms that have been identified as being involved in the irreversible process of specific neuronal death during aging are glutamate-mediated excitotoxicity, intra- neuronal calcium overload, and hydroxyl radical-induced peroxidation and oxidative damage to biomolecules." (23) Magnesium affects all of these mechanisms favorably. Magnesium also reverses the age-dependent decline in melatonin production. "The elderly may be at risk of developing a magnesium dificiency due to poor food selection, decreased absorption, diseases that cause magnesium depletion, or medications that may increase urinary loss of magnesium." (22) I therefore suggest consumption of a magnesium salt sufficient to provide 400 -800mg of elemental magnesium per day.. Example: 2 tablets of magnesium chloride (OTC: Slo-Mag) three times a day (6 total/day) with meals. IV Replacement of Hormones Known to be Deficient in AD Patients Melatonin. Melatonin is a hormone produced at night in the pineal gland. It is associated with sleep and circadian rhythm. It is a very potent and efficient endogenous radical scavenger. It reacts with the highly toxic hydroxyl radical and provides on-site protection against oxidative damage to biomolecules within every cellular compartment. Melatonin production declines in a very regular and predictable way with age. While in young animals and humans the 24-hr cycle of melatonin is very robust, the cycle frequently deteriorates during aging and is totally abolished in neurodegenerative diseases such as Alzheimer's Disease (23,). Agents that are active against the symptoms and progressions of diseases associated with accumulating oxidative damage and neuronal degeneration, such as acetyl-L-carnitine and magnesium, prevent the age-associated decline in nocturnal pineal and blood melatonin in rodents. (32) The exogenous administration of melatonin substantially extends the life span in experimental animals (32). Melatonin exerts direct and indirect beneficial effects in delaying developmental and aging processes. (28,32) "The diurnal rhythm of melatonin can be substantially perserved during aging by restriction of food intake or other nutritional and pharmaceutical treatments in rodents; these treatments increase life span and prevent premature aging as well as delay the onset of neurodegenerative diseases." (33) Melatonin has antagonistic effects on glutamate-mediated excitotoxicity, one of the three mechanisms proposed for neuron death during aging. Melatonin is a highly efficient free radical scavenger, especially of hydroxyl, thus counteracting another of these mechanisms, hydroxyl-radical induced peroxidation and oxidative damage to biomolecules. Dementia due to premature aging in patients with Down syndrome or accelerated aging in patients with Alzheimer's disease may be attributed to an enhanced exposure to hydroxyl radicals. Melatonin is the best known free radical scavenger. Additionally, melatonin reportedly exerts potent oncostatic, immunostimulatory, and rejuvenating effects in old rodents. (22) "Several lines of evidence suggest that abnormalities in oxidative metabolism and specifically in mitochondria may play an important role in Alzheimer's disease. The abnormalities include a profound deficit in the activity of the ketoglutamate dehydrogenase complex (KGDHC), which is likely to lead to impaired metabolism of glutamate and might contribute to selective neuronal cell death by excitotoxic mechanisms." (15) "The plasma half-life of melatonin is relatively short. Plasma profiles produced by oral formulations are markedly dissimilar to the typical in vivo plasma profile. In healthy young subjects, melatonin can be detected for 10-14 hr per night at a level that typically varies between 100-300 fm/ml. In contrast, bolus oral and i.v. doses typically produce pharmacological levels (in the nanomolar range) that are excreted within 2-5 hr." (34) "The difference between the endogenous profile and that produced by exogenous administration may be of critical importance. Many of the physiological effects of melatonin in animals appear to be related to the duration of the plasma profile rather than the plasma level per se. If melatonin is to be developed as a successful clinical treatment, differences between the pharmacological profile following exogenous administration and the normal endogenous rhythm should be minimized. Continued development as a useful clinical tool requires control of both the amplitude and duration of the exogenous melatonin pulse. There is a need to develop novel drug delivery systems that can reliably produce a square-wave pulse of melatonin at physiological levels for 8-10 hr duration." (34) Since there is not now available a commercial timed-release formulation of melatonin, (it should be available relatively soon), imitating the natural youthful physiologic profile should be attempted by doing two things: Take a large initial dose (say, 6-10 mg) right before bed. Melatonin will remain in the blood longer. And, if the patient wakes up in the middle of the night with at least 4 hours of sleep left, he/she should take another 3 mg capsule of melatonin. At extremely high doses (200 mg/day and above), melatonin increases depression and insomnia. At doses of around 3-30 mg/day, no known side effects are evident, other than the hypnotic effect (sleepiness). (34) Melatonin should not be taken by patients with myelocytic leukemia or multiple myeloma. Melatonin production is supressed by vitamin B12 supplementation, a supplement frequently taken by the elderly to avoid pernicious anemia. I therefore suggest nightly consumption of 6 to 10 mg melatonin just before going to sleep, and consumption of an additional 3 mg if the patient wakes up in the night with at least 4 hours of sleep to go. When timed-release melatonin becomes available, I suggest using that. Dehydroepiandrosterone (DHEA) Dehydroepiandrosterone (DHEA) is a hormone of the adrenal cortex. It peaks at around 20 to 30 years of age at 50 to 100 ug/dl, and declines thereafter at about 20% every decade after age 25, stabilizing at 5% of youthful levels at age 85. Administration of DHEA or certain analogs produces an array of beneficial effects on obesity, muscle strength and mass, type II diabetes, cholesterol levels, autoimmunity, cancer initiation and proliferation, osteoporosis, memory, and aging. It has been reported that an increase in plasma DHEA is correlated with a 36% reduction in mortality from all causes, and a 48% reduction in mortality from cardiovascular disease. (35, 43) "(It has been suggested) that acetylcholine (Ach) neurotransmitter activity manifests its physiologic action through inhibition of K+ channels in the cell membrane which serves to maintain neuroexcitatory activity. Based on this, Roberts postulated that the progressive debilitation of aging, as is seen in AD, could be due to gradual decrease in 'the capability for genetic transcription of major K+ channel components so that the ability of cells to adjust to changing conditions would be lost.' He felt that the progressive decline in the hormonal DHEA, DHEA-S levels with advancing age may be a key factor producing the debility of aging leading to AD through loss of K+ channel inhibition. The postulate that DHEA would inhibit K+ channels was based on DHEA's broad physiologic action: modulation of diabetes, tumor induction, and effects on autoimmune response which Roberts felt were key factors in preventing age-related events. Regardless of the validity of his concept, he has found that DHEA and it's sulfate in tissue culture enhanced neuron and glial survival...Robert's concept may be further supported by the high concentration of DHEA-S found in the brain (6.5 times plasma concentrations), which suggests that DHEA may have modulating effects on cell membranes which alter response to neurotransmitters." (35) DHEA and it's sulphonated metabolite DHEAS are the major secretory product of the human adrenal gland. "Reduced plasma levels of DHEA (48% less than age matched controls) have been found in AD patients. DHEA and DHEA-S enhance memory retention in mice and block the memory impairing effects of scopalomine. Besides anti-amnestic effects, DHEA-S may protect partly degenerated or at-risk brain cells." (42) "DHEA has been likened to an "antihormone", which cannot serve to excite in the true classical sense of hormone action, but deexcites metabolic processes which overproduce when DHEA is in short supply. DHEA may act by buffering or antagonizing the action of corticosteroids to modify stress-mediated injury to tissue, an action which may be critical to the diseases of aging." (43) "DHEA-S was shown to block enzymatic effects of glucocorticoids, thus, a certain part in the progression of AD may be played by the decrease in DHEA-S and its antiglucocorticoid functions." (36) "In a study of 24 AD patients and 50 controls, subjects were examined for DHEA-S/cortisol ratios. A strong negative correlation was found between age and DHEA-S, but no significant correlation was found between cortisol levels and age; therefore, the DHEA-S/cortisol ratio dropped remarkably in older normal subjects as compared to young individuals. Interestingly, a trend was found for a lower DHEA-S/cortisol ratio in AD patients compared to age- and sex-matched controls. indicating that the ratio could be an appropriate measure for the effects of DHEA-S as an antiglucocorticoid by which subjects at risk for the neurotoxic effects of glucocorticoids could be identified. These previous results suggest a possible relation of cognitive impairment to circulating corticoid levels (37, 43), and they indicate a possible role of DHEA-S in diminishing cortisol effects on hippocampal cells avoiding progressive hippocampal degeneration in AD." (38) "While the nature of possible antiglucocorticoid effects is unknown, several authors have reported physiological antagonism by DHEA of corticosteroid effects such as thymic involution and suppression of lymphocyte proliferation. We propose that, in addition to such "pharmacodynamic" effects, DHEA may have a "pharmacokinetic" effect on circulation cortisol levels. Pharmacologically induced increases in DHEA levels are significantly correlated with decreases in 4 p.m. serum cortisol levels." (39) "Physicians are testing DHEA as a possible therapy for systemic lupus erythematosus, a chronic inflammatory disease. In lupus, the immune system goes awry and makes abnormal antibodies that can damage or sometimes destroy the kidneys, brain, or heart. Experimental evidence that DHEA benefits mice that develop a lupus-like disease, coupled with the observation that DHEA levels are abnormally low in patients with lupus, led researchers to test the hormone in 57 women with lupus. The women took 50-200 mg of oral DHEA every day for 3-12 months. About two- thirdsreported some relief of symptoms including rashes, joint pain, headaches, and fatigue. 'DHEA has the potential to be an important drug in lupus, particularly because of its apparent ability to significantly reduce the need for steroids', said one scientist." (40) Thus, there are indications that DHEA administration is helpful in mitigating an autoimmune inflammatory response. AD has now been shown to have autoimmune inflammatory etiology. DHEA's anti-inflammatory effect could, therefore, be therapeutic for AD. Large-scale clinical studies are now underway of DHEA and AD patients at the National Institute of Mental Health. (41) Cognitive impairment due to endogenous hypercortisolemia may be prevented by anticorticoid hormonal treatment. (37) Chronic glucocorticoid administration leads to hippocampal damage in the rat and, due to a dysfunction of the hypothalmic-pituitary-adrenal axis, to progressive dementia. (36) "Based on animal studies, the anticipated potential benefits of DHEA replacement therapy would be: (a) increased mitochondrial respiration of the liver, (b) increased fatty acid deacylation, (c) reduced blood serum cholesterol, (d) reduced LDL cholesterol, (e) increased memory retention, (f) increases in calcium deposition and bone density, (g) increased muscle mass and strength, (h) increased skin thickness, (i) stimulation of the immune system as measured by an antiviral and antibacterial action, (j) reduced shrinkage of the thymus gland, (k) chemo-preventative activity for certain cancers (breast and colon) (l) decreased blood pressure, (m) anti-obesity action by reducing blood sugar and insulin, (n) reduced negative effects of stress, and (o) increased sex drive and performance." (42) "Possible side effects, based on animal studies at extremely high doses, are: (a) male pattern baldness, (b) hirstutism, (c) pituitary tumors, (d) liver hypertrophy, and (e) prostate hypertrophy. It is not likely that doses needed to give a blood level equivalent to a 25 year old would cause any problem. With proper physiological monitoring, the potential benefits may greatly outweigh any potential risks for many people." (42) There have been suggestions that since DHEA has an androgenic role, it might exacerbate prostate cancer, and thus tests to ensure the absence of prostate cancer were recommended proir to starting a DHEA replacement program for men. Recent studies show no effect on prostate growth (35), and DHEA had no proliferative effect on transplanted prostatic cancer cells in mice. (46) Prostate cancer tests prior to DHEA replacement are therefore probably unnecessary (they may be valuable in their own right, however).In fact, given the oncostatic and anti-neoplastic properties of DHEA, DHEA may actually help prevent and fight prostatic cancer. I therefore suggest daily hormone replacement therapy with DHEA (one capsule in the morning) to achieve youthful DHEA levels for Alzheimer's patients. Guidelines: It is important to use antioxidants with DHEA because of the possibility of oxidative stress on the liver. Uptake of DHEA varies from person to person. Because of that, testing at intervals is important to ensure proper levels of DHEA are being achieved. Step One: Get a DHEA-Sulfate blood test. A doctor must order this test. Analyze the results compared to a normal 25 year old's serum levels. Average DHEAS levels in young men are 9.2 umol/litre. Average levels for young women are 7.1 umol/litre. Average levels for both sexes age 85 and older are 1.7 umol/litre. (30) If you take too much DHEA, there could be an inhibition of the adrenal glands to produce any DHEA. Assuming you are deficient as shown by the test, initiate your DHEA intake at doctor-recommended levels. Note: given average DHEAS levels in young and old people and the standard deviation around those levels, a dose of 200-250 mg DHEA/day would be very unlikely to be excessive if you are over 70 years of age, even without an initial test for DHEAS levels. Step Two: After using DHEA for two months, obtain another DHEAS test. Have your blood drawn at least 3 hours after your normal morning dose of DHEA, and at the same time of the day as your first test (DHEA secretion varies during the day according to your circadian rhythm. Adjust your dose, if necessary. Pregnenolone "An additional approach (to ameliorating corticosteroid-associated behavioral and cognitive impairment in certain patients), involving the administration of precursor steroid hormones, has been recently proposed. The biosynthesis of steroid hormones begins with cholesterol, from which the glucocorticoids, mineralcorticoids, and sex steroids all derive. Pregnenolone, a key cholesterol metabolite, is the major precursor for the steroid hormones. Its formation, regulated by pituitary hormones, may become rate-limiting in aging, stress, and other conditions, resulting in steroid imbalances. The recent findings of a striking memory-enhancing effect of pregnenolone and literature showing virtually no human toxicity, suggest that administration of pregnenolone may help reestablish normal relations among the various steroids when abnormalities occur." (39) From the Geriatric Research Education and Clinical Center, Veterans Administration Medical Center, St. Louis, MO: "Immediate post-training intracerebroventricular administration to male mice of pregnenolone (P), pregnenolone sulfate (PS), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, dihydrotestosterone, or aldosterone caused improvement of retention for footshock active avoidance training, while estrone, estradiol, progesterone, or 16 beta-bromoepiandrosterone did not. Dose-response curves were obtained for P, PS, DHEA, and testosterone. P and PS were the most potent, PS showing significant effects at 3.5 fmol per mouse. The active steroids did not show discernible structural features or known membrane or biochemical effects that correlated with their memory-enhancing capacity. The above, together with the findings that DHEA acted even when given at 1 hr after training and that P, PS, and DHEA improved retention over a much wider dose range than do excitatory memory enhancers, led to the suggestion that the effects of the active steroids converge at the facilitation of transcription of immediate-early genes. P and PS, for which receptors have not yet been demonstrated, may exert their effects by serving as precursors for the formation of a panoply of different steroids, ensuring near-optimal modulation of transcription of immediate-early genes required for achieving the plastic changes of memory processes. Low serum levels of P in aging and the increases of cancer and behavioral disorders in individuals receiving drugs that block synthesis of cholesterol, the immediate precursor of P, suggest possible clinical utility for P." (47) I therefore suggest pregnenolone supplementation (30mg/day initially) for Alzheimer's patients. Typical dosages vary from 10 to 100mg/day. V. Anti-Inflammatory Therapy: Drugs and Oral Tolerance "The etiology of AD is unknown. Recent evidence has demonstrated that activation of inflammatory and immune mechanisms accompanies the degenerative process in the disorder...In AD, physical examination does not indicate inflammation, but more sensitive serologic and tissue studies do provide evidence of inflammatory activity....These results indicate that a process, perhaps the degeneration of brain tissue, is stimulating an acute phase response in AD...The acute pahse response, whether systemic or local, may thus be important in elevating levels of amyloid precursor protein and creating a proteolytic environment favoring the production of amyloid B protein, a component of amyloid placques associated with the disease." (48) "What initiates the pathogenic mechanisms in AD?...If there is impairment of the blood-brain barrier, previously protected brain antigens, or altered antigens, may be exposed to the immune system. Inflammatory and immune mechanisms may thus be initiated (and may be self-propagating), leading to tissue destruction in the brain. Once inflammatory mechanisms are active in brain tissue, they may contribute to disruption of the blood-brain barrier." (48) "Monozygotic twins show discordant expression of AD, indicating the importance of nongenetic factors; variation in inflammatory response may be one such factor. However, unaffected first-degree relatives of patients with AD have elevated levels of acute phase reactants in the serum, in addition to a 50% chance of contracting the disease; the the mean reactant values are intermediate between those of normal subjects and those of AD patients. If acute phase reactants are elevated in a population at high risk but clinically unaffected, the inflammatory response in AD may not be solely a reaction to tissue destruction. On the basis of the preceding mechanisms, supression of the acute phase response and inhibition of accumulation and activation of macrophages are potentially therapeutic and pharmacologically feasable." (48) "It is abundantly clear from papers submitted to this Forum (45th Forum in Immunology, 1992) that elements of the immune system are involved in the pathogenesis of the principle lesions characterizing AD. While the full spectrum encompassing typical events involved in the classical inflammatory response is not yet evident, present findings are in accord with features associated with both the innate and adaptive immune mechanisms." (49) "It appears that a prolonged exposure to the non-degradable but potentially toxic amyloid substance may initiate an immune reaction and cause cell injury that may provoke inflammatory responses." (49) "The bulk of the evidence presented points to the operation of a chronic inflammatory response which may begin insidiously as a "low grade smoldering response" that does not resemble acute inflammation. The evidence indicates tthat the inflammatory response is produced locally within the parenchyma; however, it also seems to entail communication with the circulation. Remarkably, the brain holds the capacity to produce almost all the immune system mediators which largely seem to be generated by glia composing both astrocytes and microglia (representatives of the immune system's monocytes and macrophages, which contribute to inflammatory responses). This fact beacons a fundamental change in our thinking that the brain is not necessarily immunologically privileged as first impressions would indicate, but seems to have its own immune system and can readily mount a full immune attack." (49) "Serum from AD patients contained antibodies that recognized cholinergic neuronal elements in the adult rat brain, namely the medial septum, hippocampus, and cortex. Another group of investigators showed that AD serum contained antibodies directed against the purely cholinergic Torpedo electromotor neurons. Antibodies directed against microglial cells were present in a much higher frequency in AD cerebrospinal fluid, compared to CSF from other dementia patients." (50) Anti-inflammatory Drugs Corticosteroids. Glucocorticoids are the most broadly active anti- inflammatory/immunosuppressive agents in clinical use. Steroids are the mainstay of treatment for idiopathic inflammatory diseases of the central nervous system. Unfortunately, there are serious drawbacks to clinical trials of this class of drugs in AD. The known systemic toxic effects of moderate to high doses of corticosteroids in humans are numerous. Experiments in animals have demonstrated that prolonged exposure to glucocorticoids is toxic to hippocampal neurons, and impairs the capacity of neurons to survive insults; it is feared that patients with underlying brain disease may be particularly prone to adverse effects of steroids. (48) However, with the use of markers for inflammatory activity, possible beneficial effects of low doses of steroids can be assessed. Chronic administration of prednisone at low doses (i.e., 10 mg/day or less) to elderly patients is well tolerated and effective in the treatment of systemic inflammatory diseases such as rheumatoid arthritis. (48) Nonsteroidal Anti-Inflammatory Drugs (NAID). These drugs are the first line drugs for inflammatory diseases such as rheumatoid arthritis and gout. It has been reported that the prevalence of AD in patients with rheumatoid arthritis is unexpectedly low. Using Canadian and American hospital data covering more than 12,000 patients older than age 64, only 0.39% of those diagnosed with rheumatoid arthritis had also been diagnosed with AD, whereas in the general population the same age group had an AD prevalence of 2.7%. This leads to the hypothesis that medications administered to arthritis patients, such as NAID, confer protection against AD. (51,53) Additionally, a recent study comparing the drug-taking history and likelihood of contracting AD of 50 pairs of elderly twins and found that the twin who had been taking anti- inflammatory drugs had four times greater likelihood of being the later-affected or non-affected member of the pair. Anti- inflammatory drugs used by one of the twins included ibuprofen, piroxicam, naproxen, and some steroids used in the 1950s and 1960s for arthritis but are no longer prescribed. (48,51) Indomethacin. A recent 6-month controlled trial of indomethacin in patients with AD showed stable cognitive function in the the drug-treated group and declining function in the placebo group. The study was small (14 patients in each group completed the study) and there was a relatively high rate of adverse effects from indomethacin's gastrointestinal side effects, which caused the drop-outs in the indomethacin-treated group. The other group lost 20% of the subjects due to decline in behavior to the point that they wouldn't take medicine or sit for the test anymore. That didn't happen with the indomethacin patients (51,52). "100 to 150 mg/day indomethacin appeared to protect mild to moderately impaired Alzheimer's disease patients from the degree of cognitive decline exhibited by a well-matched, placebo-treated group. Over a battery of cognitive tests, indomethacin patients improved 1.3% (+/- 1.8%), whereas placebo patients declined 8.4% (+/- 2.3%)--a significant difference (p < 0.003). Caveats include adverse reactions to indomethacin and the limited scale of the trial." (52, 53) Dapsone. "1991 brought additional evidence in favor of the inflammatory hypothesis from an unexpected source. A local government health official noted what appeared to be an extremely low incidence of dementia in a leper colony on the island of Nagashima. Following up, a study on 4000 aged Japanese leprosy patients was performed. The result: The incidence of dementia was only 2.9% in those taking the leprosy drug dapsone, which also has anti-inflammatory effects, but 6.25% among those who has not taken the drug for 5 years. Another group of Japanese researchers analysed the autopsied brains of 16 leprosy patients that had probably been treated with dapsone. They found an unusual abscence of senole plaques in the leprosy patients brains compared to those of age-matched controls. (51) Due to the renal toxicity of Dapsone, I do not recommend it's use, since there are other, much better tolerated anti-inflammatory drugs. Dapsone provides further evidence of the efficacy of anti-inflammatory drugs, however. "The rheumatologist's armamentarium offers a number of other candidates for trials in patients with AD. Potent anti- inflammatory/immunosuppressive agents such as methotrexate, azathioprine, and cyclophosphamide have proven effective in ameliorating the manifestations of lupus, rheumatoid arthritis, polymyositis, and the systemic vasculitides. These drugs have the potential to cause life-threatening toxicity, but with close monitoring, long-term administration may be feasable. Methotrexate may be the best candidate in this group for study in AD. In rheumatoid arthritis, it is highly effective and relatively well tolerated. Its mechanism of action may involve interference with the activity of interleukin-1...Interleukin-1 may be an important mediator of the microglial proliferation in AD" (48) Recommendations There is evidence of AD amelioration with the anti-inflammatory ibuprofen. Although there is no evidence for the specific antiinflammatory aspirin, in view of the above information, if no antiinflammatory drugs are currently being taken by the Alzheimer's patient, I recommend one enteric-coated 325-mg aspirin be taken with breakfast, and one ibuprofen tablet be taken with dinner. If the disease continues to progress with the above therapy, I recommend initial therapy with indomethacin (100-150 mg/day). Due to possible exacerbation of gastric problems, discontinue aspirin and ibuprofen therapy during indomethacin use. If indomethacin cannot be tolerated, then re-initiate aspirin and ibuprofin therapy, and try chronic administration of prednisone at low doses (10 mg/day or less). Commence a search for a nonsteroidal antiinflammatory drug which can be tolerated. Examination of drugs used in rheumatoid arthritis, such as methotrexate, may provide possible candidates. From owner-ageing@net.bio.net Thu Jan 12 22:00:00 1995 Path: biosci!bcm!cs.utexas.edu!howland.reston.ans.net!gatech!swiss.ans.net!newstf01.news.aol.com!not-for-mail From: sforsgren@aol.com (SForsgren) Newsgroups: bionet.molbio.ageing Subject: Re: Hair Growth Linked To Growth Hormone? Date: 12 Jan 1995 18:55:38 -0500 Organization: America Online, Inc. (1-800-827-6364) Lines: 5 Sender: root@newsbf02.news.aol.com Message-ID: <3f4fhq$qmb@newsbf02.news.aol.com> References: <3f1fki$7gi@usenetw1.news.prodigy.com> Reply-To: sforsgren@aol.com (SForsgren) Male Pattern Baldness.... ******************************************************** Power comes through the sharing of knowledge. Show your power! Scott Forsgren ********************************************************* From owner-ageing@net.bio.net Thu Jan 12 22:00:00 1995 Newsgroups: bionet.molbio.ageing Path: biosci!bcm!news.msfc.nasa.gov!kinky.eng.gtefsd.com!europa.eng.gtefsd.com!gatech!newsfeed.pitt.edu!uunet!hearst.acc.Virginia.EDU!murdoch!dayhoff.med.Virginia.EDU!jpc4e From: jpc4e@dayhoff.med.Virginia.EDU (Jonathan Paul Carson) Subject: Body Temperature Message-ID: Sender: usenet@murdoch.acc.Virginia.EDU Organization: uva Date: Fri, 13 Jan 1995 00:11:44 GMT Lines: 15 Has anyone heard of a correlation between the maintenance of a lower average body temperature and longevity? I have also heard that an age of 120 is the putative upper limit of a human lifespan. How was this number derived? Also...In the latest Scientific American there is a nice little article that has summarized some studies on the health of the oldest old--those who have survived to age 90 and beyond. The author claims that this is a particularly hardy population that has managed to avoid the "typical" routes to mortality suffered by those a few years younger (eg. heart disease, cancer, AD, etc.). So essentially, the average 95 year old may be mentally sharper and physically healthier than the average 75 year old. From owner-ageing@net.bio.net Thu Jan 12 22:00:00 1995 Path: biosci!bloom-beacon.mit.edu!satisfied.elf.com!news2.near.net!news.delphi.com!usenet From: jarice@delphi.com Newsgroups: bionet.molbio.ageing Subject: Alzheimer's Disease: A Treatment Strategy Date: Fri, 13 Jan 95 03:03:39 -0500 Organization: Delphi (info@delphi.com email, 800-695-4005 voice) Lines: 482 Message-ID: <54+7hEj.jarice@delphi.com> NNTP-Posting-Host: bos1d.delphi.com I wrote this paper for my dad, who may have Alzheimer's Disease. It is the result of about 100 hrs work on medline and at the biomedical library. Alzheimer's is in many ways accelerated aging of specific neurons in the brain. In doing research on this paper, I've modified my own anti- aging strategy, most notably by adding Deprenyl, magnesium, selenium, Coenzyme Q-10, DHEA, and pregnenolone (at the appropriate ages). I think most readers of this newsgroup will find this paper interesting. If a doctor says that there's no treatment for Alzhiemer's, the medical literature proves him wrong. It's divided into 3 parts. Any feedback would be appreciated. Alzheimer's Disease: A Treatment Strategy by James L. Rice, 12 December, 1994 Introduction Alzheimer's Disease (AD) is a neurodegenerative disorder of the central nervous system that affects almost 1 in 10 individuals who survive beyond age 65. The disease afflicts 19% of individuals 75 to 85 years old, and 45% of individuals over 85. It is characterized by cerebral cortical atrophy, neuronal loss, neurofibrillary tangles, and neuritic plaques. The primary neuropharmacologic defect involves reduced activity of the enzyme choline acetyltransferase, causing reduced synthesis of acetylcholine (ACh). Other neurotransmitters known to be deficient in AD include dopamine and serotonin. Initially, components of short-term memory and immediate recall are lost, plus a decline in other higher cognitive functions such as attention. Eventually, memory loss is so severe that patients lose the ability to care for themselves. Why Not Tacrine/Cognex? One pharmacologic approach to enhancing cholinergic function involves inhibiting ACh degradation by inhibiting acetylcholinesterase (physostigmine, tacrine). Results of studies involving this approach are conflicting: no consistent benefit has been shown in patients with AD. Although therapy with tacrine has been beneficial in some patients, it has not been effective in all cases and has the potential to cause serious adverse effects. "(With tacrine), the magnitude of the changes (in patients receiving tacrine) was small, even in responsive patients, and many patients responded only partially or not at all. Furthermore, it appears that treatment response is obtained only at higher doses on the margin of patient tolerability." (1) Tacrine appears to have marginal benefit and major side effects "43% of tacrine treated patients had increases in serum hepatic enzyme activity and 51% of tacrine treated patients had adverse events related to treatment." (1) Tacrine is the only drug approved by the FDA for use against AD. An Alzheimer's Disease Strategy A strategy against AD will, of necessity, involve elements not specifically approved by the FDA for AD, but which have either direct evidence of efficacy or a compelling rationalle for their effectiveness combined with little or no risk. In fact, most of the elements in this strategy have numerous benefits including anti- arteriosclerotic effects (slows or prevents heart disease), oncostatic and anti-neoplastic effects (helps fight and prevent cancer), immunostimulatory effects (fights disease), and possibly even extended average and maximal lifespans. The cause of AD is unknown, but there is a large and rapidly increasing number of studies indicating an inflammation response, either due to local insult or genetic mutation may be one source of the damaging processes. My anti-Alzheimer's strategy is multifaceted. Two or more compounds that operate by different mechanisms are likely to prove more effective than any single agent administered alone. The strategy is: I) Accurate diagnosis using the new eye test. (2, 3) II) Drugs or compounds shown to have beneficial effects on AD with few if any adverse effects (Deprenyl, Acetyl-L-Carnitine). III) Replacement of hormones known to be deficient in AD patients (or the elderly in general) to a level found in healthy young adults (DHEA, Melatonin, Pregnenolone), and which have generalized geroprotective or antiaging effects plus indications of efficacy against specific AD etiology. Since AD is a disease of aging, a general anti-aging, or geroprotective, strategy may prove beneficial. IV) Antioxidants (Deprenyl, Melatonin, Magnesium, generalized vitamin therapy). V) Anti-inflammatory Therapy: Drugs and Oral Tolerization I. Diagnosis Diagnosis of AD has been notoriously difficult, and it is frequently misdiagnosed. I suggest replicating the recently reported test for AD involving the ability of a highly dilute solution of the cholinergic antagonist, tropicamide, to dilate pupils in probable AD patients. The general principle of the test is that in AD, acetylcholine-producing neurons degenerate. The dilating compound tropicamide works by interfering with acetylcholine. Presumably, AD patient's eye nerve cells produce very little acetylcholine, so much less tropicamide is required to affect them. Because this test has not yet been translated into a simplified clinical test, it is important to replicate the actual experiment as closely as possible so that results can be compared directly with the experimental data. (2, 3) Procedure: 1) Call an opthalmologist affiliated with a hospital (a hospital will have the ability to prepare the dilute eye drops in a sterile environment- a pharmicist will not), and explain that you want to replicate as closely as possible the procedure described in the article: "A Potential Noninvasive Neurobiological Test for Alzheimer's Disease", Science: Vol 266, 11 Nov 1994, pp. 1051-1053 (3) Tell the ophalmologist that you will need a specially compounded formulation of tropicamide, diluted to 0.01% (normal dilution is 0.5% to 1.0%), prepared prior to your arrival for your appointment, and that you will want the patient's pupil diameter measured at intervals for one hour after administration. Reading the experiment report and getting familiar with the data recording sheets will take some time. Tell them to allow about an hour and a half for the appointment. 2) Take a copy of the experiment write-up in with you, or send a copy to the opthalmologist beforehand. Take the included graph, and blank data table with you. 3) Actual Procedure: A) Have the patient sit in a semidarkened room for 2 or 3 minutes. Measure the resting pupil diameter for 1 minute. Record the average value on the data sheet. Then administer one drop of the dilute solution of tropicamide to one eye. Note the time. Begin timing from this point. B) Examine the eye for pupil diameter for 30 seconds at the following times after drop administration and record the average value of pupil diameter on the data sheet. Times: 2, 8, 15, 22, 29, 41, and 51 min after drop administration. C) Perform the calculations indicated on the data sheet to convert raw pupil diameter measurements to percentage changes from the baseline, or initial measurement. D) Plot the percentage changes at the measurement times on the included graph. Compare the profile with the already plotted profiles of Alzheimer's patients and healthy controls. Which profile more closely matches the patients profile? E) If the profile does not indicate Alzheimer's Disease, then consider the possibility of non-Alzheimer's dementia, such as Korsakoff's syndrome, multi-infarct demetia, and dementia with an extrapyramidal syndrome, and get a doctor's advice on diagnosing and treating the problem. If the profile more closely matches the AD patient's profile, then proceed with the course of treatment indicated herein, in consultation with a physician. II. Drugs or compounds shown to have beneficial effects on AD with few if any adverse effects. Deprenyl (Selegiline, Eldepryl) (-)deprenyl is a drug with a unique pharmacological spectrum. It is a highly potent and selective inhibitor of B-type monoamine oxidase (MAO), a predominantly glial enzyme in the brain, whose activity increases significantly with age. One of the monoamines oxidised by MAO-B is dopamine. An inhibitor of MAO-B should, then, increase the dopamine content of the brain. AD is characterized by death of dopamine-producing neurons. It is the only safe MAO inhibitor which can be administered without dietary restrictions. Additionally, maintenance on deprenyl enhances selectively production of superoxide dismutase (SOD). A highly potent enzyme antioxidant, SOD promotes catalase activities in the striatum, and facilitates the activity of the nigrostriatal dopaminergic neurons (the most rapidly aging neurons in the human brain) with remarkable selectivity. It prevents the characteristic age-related morphological changes in the neuromelanin granules of the neurocytes in the substance nigra. (18) Male rats maintained on deprenyl lived longer (198 weeks average vs. 147 weeks for controls in one trial- a 35% increase in average lifespan; in another trial, average survival time increased from 115 to 134 weeks[18]) and showed improved performance in learning tests (rats treated with deprenyl improved 400% in a specific test administered over one year, while the control rats performance declined 12%). Patients with Parkinson's disease given deprenyl chronically from diagnosis required levodopa on average 550 days after diagnosis. Patients not given deprenyl required levodopa in 320 days. Patients with Parkinson's disease maintained on levodopa (a dopamine precursor) and deprenyl (10 mg daily) live significantly longer than those on levodopa alone. Continuous administration of deprenyl improves the performance of patients with AD (4,5). "Deprenyl increases the activity of the nigrostriatal dopaminergic system and slows its age-related decline. Maintenance on deprenyl improves significantly the performance of patients with AD. It is concluded that Parkinson's disease and Alzheimer's disease patients need to be treated daily with 10 mg deprenyl from diagnosis until death, irrespective of other medication." (6) "It is hoped that the conspicuous harmony between animal and human data will give convincing ground for the proposal that the maintenance on small doses of (-)deprenyl (10-15 mg weekly) from the age of 45 years is reasonable and that continuous (- )deprenyl (10 mg daily) in Parkinson's and Alzheimer's Disease is, irrespective of other therapies, not only justified, but definitely mandatory." (6) "The nigrostriatal dopaminergic neurons which contain 80% of all dopamine are the most rapidly aging neurons in the human brain. The dopamine content of the human caudate nucleus decreases enormously after age 45 by about 13% per decade. Symptoms of Parkinson's disease appear if the dopamine content of the caudate nucleus is less than 30% of the youthful level. Thus, the aging of the striatal dopaminergic system is nromally slow enough to avoid the appearance of such symptoms within the average lifespan. In 0.1% of the population, however, the system deteriorates fast enough to cross the critical threshold while the patient is still alive, and the symptoms of "shaking palsey" are precipitated. MAO contributes to this decline in dopamine by catalysing destructive reactions (oxidative deamination and O-methylation). Also, when dopamine oxidises, it produces substantial quantities of toxic free radicals and highly reactive quinones, which then attack the nigrostriatal dopaminergic neurons. The waste products of these reactions are thought to be what makes up the "age pigment", or lipofuscin, which accumulates in the brain with age, and which may interfere with it's functioning. The organism survives in the face of these attacks only by the ability of superoxide dismutase (SOD) to counteract the free radicals. Deprenyl enhances the production of SOD in the striatum of rats." (6) Regarding cognitive enhancers, of which deprenyl is one, "A review of the literature points out that the day-after approach of treatment (once severe neuropathological damage has been established) is no longer feasable, or has limited advantages. A different pharmacological approach, based on preventive measures during the first stages of the neurodegeneration, seems mandatory." (7) "Regarding the consequences of the protecting effect of deprenyl in healthy humans against the age related decline of the striatal dopaminergic system, it is worth considering that just a small change in the rate of decline, e.g. from 13% per decade to 10% per decade, anticipates at least a 15-year extension in average lifespan and a considerable increase of the human maximum possible lifespan, which is now estimated to be 115-120 years, to 145 years. Preventive deprenyl medication may also retard the precipitation of Parkinson's and Alzheimer's diseases in the endangered population." (6) "The beneficial effect of prolonged treatment with deprenyl on learning and retention in selected low performer rats is in accordance with the rapidly growing unequivocal clinical evidence that the administration of deprenyl improves the performance of Alzhiemer's patients significantly. The pharmacological profile and the safety of deprenyl allowed the conclusion that in Parkinson's disease and Alzheimer's disease 10 mg of deprenyl daily should be administered from diagnosis until death, independent of any other kind of medication." (8) Side effects of Deprenyl may include elevated dopaminergic symptoms and elevated liver function enzymes. However, the risk of serious hepatic toxicity is little or none. Other reported side effects include nausea (14%), dizziness(12%), abdominal pain(4%). None of the side effects were bad enough that treatment was discontinued. (9) Deprenyl (5 mg) should be taken with breakfast and lunch to avoid reported insomnia with evening dosing. (10) "Selegiline (Deprenyl) seems to be safe in combination with low- dose tacrine and it may reduce the dose of tacrine needed for a positive treatment response in AD." (11) "16 out of 18 available reports of clinical studies (including pen, comparison, and double-blind, placebo-controlled designs) with a total of approximately 790 AD patients, with 450 treated on selegiline from one to 12 months, indicate that selegiline in addition to providing a potential symptomatic therapeutic efficacy, may retard the progression of AD." (12) I therefore suggest 10 mg of deprenyl be taken daily (5 mg with breakfast, 5 mg with lunch) for any Alzheimer's patient. Acetyl-L-Carnitine "Acetyl-L-Carnitine (ALC) is the acetyl ester of carnitine, a naturally occurring substance that acts as a carrier of fatty acids from the cytosol into the mitochondrial matrix where they can be subjected to B-oxidation. ALC is freely exchanged across membranes and can provide acetyl groups from which to regenerate acetyl-CoA, therefore facilitating the transport of metabolic energy. ALC, unlike L-carnitine, easily enters the brain. Experimental studies have demonstrated that ALC promotes Acetylcholine synthesis and release." (13) "Defects in cholinergic neurotransmission do not, by themselves, constitute the sole pathophysiologic concomitants of AD. Recent findings point out that abnormalities in membrane phospholipid turnover and in brain energy metabolism may also characterize AD. ALC is an endogenous substance that, acting as an energy carrier at the mitochondrial level, controls the availability of acetyl-L-CoA. ALC has a variety of pharmacologic properties that exhibit restorative or even protective actions against aging processes and neurodegeneration. A review of a series of controlled clinical studies suggests that ALC may also slow the natural course of AD." (13) "In open studies, ALC has been administered to patients affected by cognitive impairment or true AD. ALC proved to be safe and well tolerated, inducing only minor and transient side effects (agitation, gastric upset). Therefore, a series of double-blind, placebo-controlled trials have been performed for better defining ALC's efficacy in patients with AD." (13) In nine trials from 1985 to 1990, where daily doses of ALC from 1 to 3 grams were administered, very good efficacy was obtained in four of the studies, good efficacy was obtained in one, some efficacy was obtained in two, and a mild negative efficacy was obtained in one. (13) Generally, ALC slowed but did not stop the deterioration in cognitive function. "Although further insights into the mechanisms underlying the ALC effect are needed as are additional controlled trials on a larger number of AD patients (currently in progress), we believe that preclinical and clinical evidence supports the hypothesis that ALC has therapeutic impact on the progression of AD." (13) "There were no major adverse side effects associated with administration of Acetyl-L-Carnitine." (14) "Treatment with L-carnitine, a manipulation designed to mitigate consequences of a mitochondrial abnormality, normalized several non-mitochondrial abnormalities in cultured Alzheimers cells." (15) I therefore suggest the consumption of 2 grams of Acetyl-L- Carnitine daily in three divided doses by AD patients. III. Generalized Antioxidant Therapy "Reactive oxygen metabolites (ROM), namely superoxide and hydroxyl free radicals and hydrogen peroxide, are produced as a consequence of the physiological metabolic reactions and functioning of the central nervous system. ROM have also been implicated in the aetiopathogenic processis of a number of pathological conditions of the brain. While primarily indirect, evidence for this view is accumulating, and credence for the participation of free radical oxidative interactions in promoting tissue injury in such conditions as brain trauma, ischaemia, and toxicity, and in neurodegenerative diseases such as Parkinson's, Alzheimer's dementia, multiple sclerosis, and lipofuscinosis, is growing. Concomitant with this new understanding of the injurious role of free radical oxidants in neural pathology, is the increasing appreciation of the need for both fundamental and clinical research into the development of the potential preventative and therapeutic benefits that are now being foreseen for a variety of antioxidant nutritional and pharmacologic interventions." (16) "Compelling evidence suggests that cerebral deposition of aggregating B-amyloid protein may trigger the neurodegenerative cascades of AD, down syndrome, and, to a lesser degree, normal aging. We propose further that free oxygen radicals are critically involved in B-amyloidosis. Apart from the established role of free radicals in other amyloidoses, this is consistent with a large number