Paris IPSEN conference

Samuel Cronin samuelc at
Fri Apr 26 05:32:47 EST 1996

I am resending the following report as I think it may not have got through
first time. If it has already arrived then I appologise for cluttereing up
your mail box.

Dear all, 

Last friday April 19 I attended a one-day symposium in Paris
titled 'Longevity: To The Limits and Beyond' which was hosted
by Foundation IPSEN. The timing and setting of the Paris
conference was particularly appropriate following the recent
recognition of Mme Calment's claim to be over 120 this year.
Since many of the topics discussed during this meeting would be
of interest to the members of this list I have written a summary
of the exchanges which took place.

The general theme of all the discussions were based on the
current global trends towards decreasing mortality and higher
life expectancy, and to try to answer the question as to whether
or not there is a limit to human life expectancy and if so what
is it? It was well attended by 100-150 researchers with speakers
representing both demographers as well as biologists including,
among others, Jay Olshansky, Jim Vaupel, Jacques Vallin, Tom
Kirkwood, Francois Schachter, Raj Sohal, Tom Johnson and Caleb
'Tuck' Finch.

First up was Jay Olshansky who put forward his argument that,
as previously found in the US, in France there appeared a
practical limit as opposed to biological limit) to life
expectancy. This was convincingly portrayed with data that
showed that in order for the life expectation of the French
population, as well as the populations of other developed
nations, to increase there would have to be a disproportionate
decline in mortality. He pegged the practical limit to mean life
expectancy (LE) at birth in France at about 85 which to be
achieved would require a decline in mortality of just over 50
percent. An important point made was that although simple
extrapolation of mortality/LE trends suggest this to be
attainable, such predictions do not consider the biology of
populations. For example, to reach an LE of 100, 18 percent of
the population would have to live beyond 120 years (the
currently accepted 'limit' to human maximum life span (MLS)).
Consequently, such trends could only be maintained following
elimination of all cardiovascular diseases, cancer and the other
significant killers. He concluded that although there is nothing
we can do *today* to increase LE beyond 85 years, an LE beyond
85 may be achieved if significant medical and scientific
breakthroughs were made that allowed successful medical
interventions in disease and deceleration of the basic rate of

Next up was James Vaupel who began his discussion by boldly
stating that he believed that 'the average baby born in France
today will live to 95-100', his confidence apparently unshaken
by the previous speakers line of reason. However, I regarded the
ideas presented by Vaupel not be too far removed from Jays
conclusion, since he expressed his deep belief that mortality
rates will continue their current rate of decline due to the
likelihood of future breakthroughs in science and medicine over
the lifetime of today's babies that will be of the same
magnitude as those seen during the last century. Quite rightly
he exclaimed that 'the future has proved to be not only
unexpected , but to be surprisingly unexpected'. He also
presented data which suggested that the recent increases in the
probability of reaching late ages (ie. 60, 85, 95) is increasing
at a greater rate for later ages. He regarded this and other
results to discredit the commonly held belief that death at
older ages are mostly intrinsic, and that its almost impossible
to reduce intrinsic causes of death.

Jacques Vallin then took a flight of fancy and speculated on the
consequences of a 150 LE and models of fertility on future
population size. Although I was not familiar with some of the
models he used I couldn't help but get the impression that their
complexity could not be justified by the apparent lack of raw
data. Nevertheless, some predictions made included a 'stable'
world population of 118 billion (150 LE/2.5 children per woman)
by the year 2315 (sic), more than double that predicted if LE
is 85. Also, age structure of a population with an LE of 150
would result in <1 percent under age 20 while > 85 percent over
100 years old. 

The biological perspective of a limit to maximum life span (MLS)
presented by Tom Kirkwood brought many feet back down to the
ground but certainly did not rule out the potential of
modulation of senescence through biomedical interventions. Tom
also introduced the (so far neglected) evolutionary perspective
of _why_ ageing occurs and how this enables the question of
_how_ ageing occurs to be determined. He explained that the
optimisation of reproductive fitness through the balance between
somatic maintenance and reproduction (the disposable soma
theory) was modulated by the expression of genes involved in
maintenance of the soma and whose combined force provided a
particular 'longevity assurance' for that organism. He was of
the opinion that for any organism with a particular longevity
assurance there was an intrinsic limit to MLS in any given
environment, but that changes in these underlying genes either
through selection, transgenics, or  by changes in nutrition,
exercise or biomedical intervention may allow modulation of MLS. 

This was followed by a series of talks on the emergence of
centenarians and supercentenarian, the trends in their mortality
between the West and East (China), and broad differences in
their health presented by Jeune/Kannisto, Zeng and Forette
respectively. Then there was a special presentation of the first
ever Foundation IPSEN prize on Longevity, a new award which each
year will be given to a scientist in the field of ageing and
longevity, be he biologist demographer or otherwise. This year
Caleb Finch collected the award in recognition for his
exceptional work on the neuroendocrinology of ageing, and his
seminal text on longevity, senescence and the genome.

During the lunch intermission I spoke with, Jay Olshansky about
his views on the possibility of significantly extending human
lifespan in the future. I was  interested to find out that he
considers himself an optimist even though his research predicts
small improvements in LE. If any advances were going to occur
then he felt they would probably come from developments in
pharmaceutical and the creation of new drugs or medicines along
the same lines of Melatonin and DHEA. 

The presentation by Francois Schachter covered the goals and
some early results of the Chronos Project: the collection and
analysis of blood samples from centenarians to create a database
of certain characteristics strongly associated with long living
individuals. One interesting finding was that certain HLA types
are more common in centenarians than in controls, in particular
DR1, DR11, DR13 in male and DR7 in female centenarians. 

The concluding three talks began with Raj Sohals transgenic
fruit flies overexpressing both catalase and Cu-Zn SOD: two of
the most well characterised genes involved in oxygen free
radical scavenging. He found their joint effect to be much
greater than the effect of each gene  overexpressed on its own
with extension in MLS between 70-100 percent. More importantly
there also appeared to be an improvement in 'healthspan' with
the flies exhibiting greater mobility into old age, a delay in
the onset of the inability to fly and an improved response to
X-ray exposure. 

This was followed by discussion on the significant extension of
MLS of more than 100% in the nematode C. elegans by a mutant
form of a gene called age-1 by Tom Johnson. He explained that
this result is very exciting since in means we 'might be able
to significantly extend lifespan of even higher lifeforms
(including humans) by single gene manipulations'.  When
questioned whether he would expect to see lifespan extension in
humans of the same scale found in C. elegans he replied that he
it is very possible to achieve equally dramatic effects in
humans and that although development of the technology to
accomplish this feat may take 5 years or 100 years, he sees it
one day becoming a reality. He had also found several other
genes such as daf-2 and spe-26 which produced similarly
impressive results, and was near to cloning age-1. 

The final speaker was tuck Finch who provided some interesting
insights into the causes of non-genetic variations in life span;
why there is a > five fold variation in lifespan among
genetically identical individuals maintained under identical
conditions. The main thrust of his argument was that random
events during early development set absolute limits to the
functional lifespan of certain organs. Included among these were
the initial size of the cell pools of oocytes (determining
length of reproductive period in females), neurons (determining
the threshold of neuron loss beyond which major dysfunctions
emerge) and stem cells from which immune cells are derived. This
has obvious implications for Alzheimers disease were there
appears to be great losses of neurons. One factors suggested to
effect cell pool size during development was influences from a
neighbouring fetus. Such limiting factors were observed in both
mice but not in C. elegans in which cell numbers are strictly
controlled to ensure each individual has the same amount, which
suggests mammals and lower life forms may differ in the origins
of these non-genetic variations in LS.

Generally, I found the conference to be a really great
combination of views  - many conflicting - and despite being
only one day a lot was covered. The conference will be repeated
next year and I hope to go again. Anyway, I hope some of the
discussions that took place at the Paris conference may be
continued on this list. 

Best regards,

Sam Cronin

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