Re: Cornering the causes of aging (was Re: AGING: Accumulation of DNAdamage)

From: CYMM (
Date: Wed Jun 28 2000 - 06:43:52 MDT

Well, Joao,

Given your definition of senescence you might not have a stronger case for
isolating the "causes" of ageing.

These processes are strongly coupled in multiple feedback loops

The fact that you alter ONE gene and it makes a massive difference does NOT
say that it's THE master gene. Case in point: if you lower serum cholesterol
substantially (say down to under 110mg/dL... coronary artery disease ceases
to become a statistically important killer in the population at large.

Does that mean that high cholesterol is THE mechanistic "cause" of such
heart disease?... far from it.

Certainly, by altering genes related to insulinlike resistance or genes for
SOD and catalase you can extend the lifespans of mice, fruitflies and even
worms...and by supplementing with things like CoQ10 you can increase average
lifespans of mice... but the processes are so wickedly coupled that the only
biological way you'll get to that 1,000 year birthday is by modifying the
action of dozens or scores or thousands of genes.

As you extend the lifespan horizon you're going to collide with even more
forbidding barriers to eternal youth... barriers that are not directly
placed by simple darwinian restrictions on optimum individual reproductive
lifespan, but that arise from the fact that we metazoans are all clonal
colonies. You'll have to keep redesigning the entire genome as you push the
threshold back...

Already, there is some evidence that ageing in the "young old" is of a
different nature than ageing in the oldest old. The oldest old are a genetic
elite who have withstood the killing processes that plague us early on.

But they die nevertheless...and the mechanism of their ageing seems
different. Overtly cellular processes as opposed to system processes seem to
kick in. So we may end up peeling an onion in the quest for biological

As to your chaos theory thing, "Chaos theory says that simple phenomenon has
origins"... I don't know. The most interesting thing about complexity theory
is that complex systems display emergent behaviour on a massive scale.

It's precisely for this reason that it's hard to isolate simple causes. Our
naive notions of causality break down when the system displays strong
coupling and largescale emergent behaviour.



-----Original Message-----
From: Joao Pedro de Magalhaes <>
To: <>
Date: Wednesday, June 28, 2000 7:28 AM
Subject: Re : Cornering the causes of aging (was Re: AGING: Accumulation of

>>JOAO PEDRO SAID: "...One of the major failures of gerontology has been in
>>cornering where are the causes of aging located...."
>>CYMM SAYS: That's not strictly true, Joao. If it's one thing that
>>gerontology has taught us is that ageing - and the diseases of ageing -
>>MULTIFACTORIAL in aetiology.
>>If you're looking for one major "cause" and one major "cure" for "ageing"
>>you'll never find it. The "failure" lies in the interrelating of the
>>multiple factors to produce a very useful medical model.
>You're saying that aging is the sum of all genes affecting age-related
>diseases? I don't agree. I think many age-related diseases evolved pararell
>to aging but are not senescence. (I define senescence as the basic and
>intrinsic aging process, independant of all diseases.) And this process can
>well be a very simple mechanism. Just look at some progeroid syndromes and
>how simple they are originated; or look at the large diversity in lifespan
>and aging phenotypes in many phylum (including mammals), if aging had that
>many genes affecting it, these differences would not exist. There are more
>genes affecting age-related diseases than are genes differentiating us from
>As for experimental evidence, I can cite you the recent lifespan extension
>of almost 40% in mice by changing a single gene (in which senescence was
>clearly slowed down). Chaos theory says that simple phenomenon has simple
>origins; senescence is a very simple phenomenon (an exponential increase in
>mortality from age 19 until age 70), so it can well have a very simple
>Best wishes.
>Joao Pedro de Magalhaes
>The University of Namur (FUNDP)
>Unit of Cellular Biochemistry & Biology
>Rue de Bruxelles, 61
>B-5000 Namur BELGIUM
>Fax: + 32 81 724135
>Phone: + 32 81 724133

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