Earlier I wrote:
> We may all rely on the same processes, but there's considerable
> variability in how much and how well we use them. Your heart disease
> through fat example illustrates this. The APOE (apolipoprotein E) gene
> has several alleles but one (e4) is associated with early atherosclerosis
> and another (e2) is associated with hyperlipidemia. Get two copies of
> the e3 allele and you'll probably never suffer atherosclerosis no
> matter how much fat you eat.
Since I wrote this, I've discovered a paper in Nature Genetics that
shows that the effects of these alleles are not at all what might have
been predicted from earlier studies. It seems that having e2 gives you
TWICE the chance of making it to 100. Wacky huh? Hold that fat.
This doesn't change my comments on the role of non-universal intrinsic
differences in the aging of individuals but it does illustrate how
difficult it will be to isolate individual processes: Like atherosclerosis
most processes will be seriously polygenic.
Which brings me to comments by Chris Driver
In <drierac.56.001272DA at deakin.edu.au> drierac at deakin.edu.au (Chris Driver) writes:
>In article <3ZGevA7CBh107h at chambers.ak.planet.co.nz> steve at chambers.ak.planet.co.nz (Steve Chambers) writes:
>>That doesn't necessarily follow, especially if there were enough of 'em
>>and they were all "common". To illustrate the point let's assume there
>>are 100 aging processes (I believe there are more) and any human has a
>>30% chance of each. Assuming random distribution the prob. of being subject
>>to no process is 0.7^100 or one chance in around 30,000,000,000,000,000.
>>It's not going to happen very often.
>>The above dynamic may explain lifespan distribution, or it may not. By
>>saying that an aging process NEED not be universal I certainly don't mean
>>to imply that NO aging process is universal.
>I am not convinced: it should be possible to select for absence of A, then B
>then C and produce an animal which lives very much longer.
1) To select for the absence of A you first need to know what A is.
2) You then need to find some way of selecting for [not A]. That could
be a difficult (and expensive task). As an exercise, think of an
easy way to select for APOE allele e3 in the above example.
3) Once you get to M you may still find that you've failed to increase
maximum lifespan (in much the same way that medicine has failed to
increase it for humans). Funding by now would be a serious problem.
4) When you've finally selected for [not A-M] you'll almost certainly
have removed alleles necessary for several of [not N thru Z ...]
Possible? Maybe, but certainly not practical and:
5) If no process turns out to be universal (not a chance) and by some
miracle you succeed in isolating an "immortal" mutant, what you've
discovered will only be partly applicable to human beings.
And remember, to even get to step (1) science will need to accept a
a radical redefinition of what constitutes an aging process.
>In fact if you select for longevity in Drosophila, you can easily
>obtain a modest increase in lifespan and then you hit a wall.
That's not surprising, and it fits well with a multiple process model,
as does Carey et al's medfly study where death rates are dramatically
_reduced_ at old age in large cohorts.
>Perhaps you accept a modified version. There are a number of deteriorative
>processes which effect everybody, although the relative rate of progression is
>slower in some than others. For instance cardiovascular degeneration occurs in
>all people, but in some it is so slow that they die of something else first.
>This means that cardiovascular disease is one ageing process.
Cardiovascular disease is too broad an example. It's no doubt contributed
to by several processes - some of which will be universal. Its biggest
contributor, the formation of atheroma is different story, however. It's
common but not universal in humans and it occurs in very few animal
species - so its (hopefully few) component processes are plainly not
But I agree that variation in process rate will probably explain most
of the heterogeneity we see in aging.
There's been some discussion at crossed purposes since my initial post
on defining aging processes. These comments describe my understanding
of the terms I use - perhaps they should have been an addendum.
Aging or ageing is that universal phenomenon that unless otherwise
specified applies to whole organisms. Senescence - ditto, but it can
also refer to clones or cell cultures. Cellular senescence for me is
just that - cellular senescence. I know that the "cellular" is usually
redundant between molecular biologists but I try never to drop it - or
I'll lose sight of the "big picture". I never use the term immortal to
refer to a cell because there's no such thing. I might call it
immortalised, but that's descriptive of a change it's been through and
quite a different matter. A cell line or clone can be immortal however.
Downunder English is it's own entity variously influenced by English
English and American English and scientific Downunder English is very
much flavoured by the usage (or lack thereof) of local scientists. I
can remember one of my lecturers, for example, not knowing what the term
"Hayflick limit" meant. He'd just finished discussing doubling potential!
Someone tell me if my use of these terms is inappropriate.
(I_lurk,_therefore_I_am!_\ ,,, Steve Chambers
(o o) steve at chambers.ak.planet.co.nz
(c) Steve Chambers 1995. All rights reserved