>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.
I wasn't saying that p66 (the gene leading to 40% life extension in mice)
was the cause of aging. I was merely pointing (as there are other examples)
that senescence might not involve so many genes as you're saying. I agree
many genes affect aging. But if we can eradicate senescence probably most
age-related diseases will disappear; while some will remain and we'll
afterwards need to eliminate them too.
>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
I agree. But we have to take one step at a time. First end senescence, then
take care of the other diseases (what I call post-mortem lethal genes).
>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
I find that hard to believe. Do you have any data showing different causes
of death in centenarians and people, say, from 65 to 100? I don't think you
do. Until further evidence I follow Occam's razor: 1 cause of senescence
instead of 2.
>Lastly, in species where death by predation, misadventure etc. is high and
>thus there is no real "danger" of loading the gene pool with oldies (...the
>survival curve will be exponential anyway!!) we should sometimes see
>long-lived non-ageing species. Maybe sea turtles; carp; and certain catfish
>fit this model to a certain extent...
>But then they STILL eventually age and die when captive reared in suitable
>habitats. Is ageing different then... are they coming up against cellular
>ageing constraints specific to the genetic complexities of being a metazoan?
That's new! Do you have any references showing Marion's tortoise's aging in
captivity? Or the Galapago's tortoise? Or lobsters? Or rockfishes? I've
never read one single paper showing aging in any of these species, either in
the wild or in captivity. Besides, I didn't get your argument of species
with higher mortality being the ones where one can most easily find
long-lived and non-aging individuals?!
>Just because you can find several instances where fixing up ONE gene can add
>another 50% or 100% to maximum lifespan does not mean that INDEFINITE life
>extension is easy... on the contrary the finding that fixing any one or two
>of a set of many totally different genes can do this... seems to indicate
>that a very complex system is at work...
Of course there are backup-ups and overlapping pathways but finding single
genetic lifepan determinants (of over 50 or 100%), as I said before, is
what's expected if aging is governed by a simple mechanism (and it is not
expected if aging is governed by thousands of genes).
>Fixing such systems so that they'll achieve biological immortality seems to
>me well nigh impossible.
What a lack of vision and ambition! Even if you are right, you can't be sure
of it and should well damn try to end aging. I'm a gerontologist and I might
fail in my mission but I will never give up.
>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); (2)
Occam's razor: what's easier to evolve, 100 mutations for age-related
diseases or 10 mutations upstream of age-related diseases; (3) Gompertz'
curve is not a rough one; in human populations it shows a good correlation
(see Hayflick's book) (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; (5)
despite what I said in (1), in mammals that is not true. 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. Yet
mice -- with maximum lifespans of 5 years -- have roughly the same diseases
we do at age 65. And the best (and simpler, I'm sure you can think of other,
more complex and therefore more unlikely, explanations) explanation is that
there is a single mechanism causing aging in mammals that in turn leads to
all age-related diseases. (You might be confused of what I said in (4) but,
although (4) is true, the fact is that the statistical distribution of
age-related pathologies and causes of death in captivity is quite similar
amongst mammals; there are punctual differences: for example, mice have
higher incidences of kidney failure than humans; but in general this is true
for all well-studied mammals.)
>> the negative benefits of loading the genepool with archaic combinations in
>> the face of rapid environmental change....
>Man, it seems like I have this argument a lot! That's
>not really a problem; if the archaic combinations are
>bad, the possessors will be dead anyway. Often, the
>archaic combinations will carry valuable information
>which is being lost due to fluctuating selection or drift.
Read Bowles J, 2000. He makes a good argument against what you just said.
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
Reason's Triumph: http://users.compaqnet.be/jpnitya/
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