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

From: CYMM (
Date: Thu Jun 29 2000 - 17:46:08 MDT

Joao's thesis is essentially that senescence must be due to a small set of
root causes because of the following empirical data:

(1) altering one or a few genes can markedly increase maximum lifespan, eg
SOD/catalase genes

(2) related taxa can differ markedly in maximum lifespan, eg, Pan & Homo;
Rivulus & Cynolebias; Salmo spp.

...but the logical fallacy here is plain: just because altering one
"controlling" parameter changes another system parameter markedly in one
direction; we cannot assume that the system has a tiny set of such
"controlling" parameters for that latter system parameter.

The empirical data that Joao cites certainly does not rule out his
hypothesis but it also does not lend any support whatsoever. It is logically
unrelated to his hypotheis.
On the other hand, the assumption that metazoans are potentially infinite
lifespan entities in the absence of a few genetic faults is suspect on
biological grounds.

The genetic machinery necessary to produce the specialization & coordination
found in an advanced metazoan is enormous.

Such highly coordinated systems are especially failure-prone because of
their complexity. In vivisystems the naturally high-coordination,
decentralized "design paradigm" does allows graceful failure of an
individual system.

But that is all.

Robustness and immunity from failure are two quite different things.

To evolve a near-eternal organism in this scenario, the fitness of the
immortality phenotype would have to be truly enormous. The modifications to
the underlying genetics - to yield such a phenotype - would be truly


-----Original Message-----
From: <>
To: <>
Date: Thursday, June 29, 2000 5:11 PM
Subject: Re: Re : Cornering the causes of aging (was Re: AGING: Accumulation
of DNAdamage)

>In a message dated 6/29/00 5:41:04 AM, writes:
>>CurtAdams wrote:
>>>If you have *nothing* but a variety of accumulating late-acting
>>>pathologies, that alone will create "aging": increasing mortality
>>>plus decreasing function accumulating thoughout life, following
>>>a roughly Gompertzian curve. So the pathologies can indeeed be
>>>the basic cause of aging.
>>No, the phenotype of aging does not indicate such an origin. I'll tell you
>>why: (1) the large differences in aging phenotypes amongst closely-related
>>species indicates simple mechanisms (for example, amongst teleosts);
>I don't get this reference. Are you talking about lifetime vs. one-time
>reproduction in salmon?
>>(2) Occam's razor: what's easier to evolve, 100 mutations for age-related
>>diseases or 10 mutations upstream of age-related diseases;
>Every system and most genes can evolve some kind of age-related problem.
>All of these problems will thus be in mutation-selection balance with
>the "optimal" alleles. Any metazoan population will necessarily be
>for thousands of age-related deleterious alleles. Alleles which
>combine several systems together are much more difficult to evolve;
>the population isn't spewing out thousands per generation. There is
>no way to avoid this.
>>(3) Gompertz'
>>curve is not a rough one; in human populations it shows a good correlation
>>(see Hayflick's book)
>What we see is what's predicted; close to a Gompertz most of the time;
>not a Gompertz in youth or old age.
>>(4) there is only one age-related dysfunction
>>(presbyopia) that affects all humans; so, unless thousands of back-up
>>pathologies are constantly at work, your argument does not stand;
>There *are* thousands of pathologies. The phenetic variability of
>aging is a problem for *your* theory; you're the one claiming we
>all have the same aging system.
>>(5) despite what I said in (1), in mammals that is not true.
>You've got to make up your mind here. If similarity of aging is evidence
>for your theory, variability (1) is evidence against it, and vice
>>Mammals have a
>>large amount of similarities in the aging process (read Finch's book for
>>references). If aging is just the diseases that evolved due to lack of
>>evolutionary pressure in old ages, then larger differences are expected.
>>mice -- with maximum lifespans of 5 years -- have roughly the same
>>we do at age 65. And the best (and simpler, I'm sure you can think of
>>more complex and therefore more unlikely, explanations) explanation is
>>there is a single mechanism causing aging in mammals that in turn leads to
>>all age-related diseases.
>No; the simple explanation is that *everything* goes wrong. Mammals are
>all biologically very similar; they have the same things to go wrong.
>Non-replaceables wear out; proliferation slows, impairing repair,
>and cancer becomes more common. These are all very straightfoward.
>>Read Bowles J, 2000. He makes a good argument against what you just said.
>Erk! Didn't you notice that was in Medical Hypotheses? It didn't even
>rate Mechanisms of Aging and Development. I can't get the article, because
>UC Riverside has never gotten that journal and UC Irvine hasn't gotten it
>since 1991. But just looking at the abstract shows me several problems:
>B>A new thought experiment with competing strains of algae
>B>corrects for these issues and shows that aging evolved and is
>Well, thought experiments aren't adequate. If you want to support demic
>selection, you need to do the population biology or quantitative genetic
>models, like Goodnight or Wade do.
>B>retained so that groups retain enough genetic variability to allow
>B>for rapid evolution of a defense to novel predation.
>This is a serious error. Aging won't preserve genetic variability, it
>will reduce it. Neutral variation will be the same. Near-neutral
>variation will be *less* in the aging population, due to faster turnover.
>When a novel situation comes along, the aging population will *more*
>likely have lost the genes to deal with it.
>>The hypothetical
>>antagonistic pleiotropy genes that are beneficial to young while
>>detrimental to old individuals, predicted to exist in the 1950s, are
>>unlikely to exist, have not, and likely will not be found in
>>sufficient quantity to participate in the aging process.
>He needs to read the literature: there have been many demonstrations
>of antagonistic pleiotropy. Offhand, I can recall Rose's and Partridge's;
>there are many, many others.
>He doesn't mention that an aging population will be far less fit just
>because it has a higher death rate. If the situation is dire to the
>point a non-aging population can barely make it, the aging population
>will have negative growth due to the extra mortality, and will go
>P.S. I'm not knocking Medical Hypotheses; there's a role for such
>journals. It's just that things published there aren't really evidence
>for anything.

This archive was generated by hypermail 2b29 : Thu Jul 27 2000 - 14:14:46 MDT