I see an analogy between what you call programmed death and what I’m calling pro-aging processes, but I am thinking of things like the down-regulation of DNA repair and antioxidant defenses by IGF-1 early in development, which may have the effect of accelerating aging and speeding death in late life. I think that by simply re-regulating such pro-aging pathways to a state that is more protective, we can in principle do much to intervene in human aging in a meaningful way. Since I can’t think of any deep benefits of oxidative damage and DNA damage offhand, its seems like correcting this pro-aging state would not have to have much in the way of side effects, either. The value of model systems like C. elegans in this regard is that they provide a proof of principle to the degree they can, in that blocking pro-aging pathways in C. elegans can increase the lifespan by a factor of 10.
On Monday, February 2, 2015 3:55 PM, Robert Young wrote:
By “pro-aging processes” I assume you mean “programmed death,” which is common in many insects, annual plants,
Reversing the “low-hanging fruit” deaths attributed to these death programs is not really the fight against “intrinsic aging,” which is what concerns us humans. So, I agree that the life extension of such things as fruit flies and nematode worms doesn’t come close to comparing to what it will take to slow and eventually reverse the processes of intrinsic aging in mammals.
From: Gregory M Fahy To: Gerontology Research Group Sent:
Monday, February 2, 2015 3:43 PMSubject: Re: [GRG] Longevity lessons from Brandt’s bat, the little brown bat, and the naked mole-rat
I believe Michael Rose would argue that longevity IS selected for, and in the case of the naked mole rat, which I believe does not show reduced fertility with age, the
longer they live, the more offspring they have, and so longevity should be selected for. In a sense, the NMR is like the bowhead whale and the Mcaw in that all have virtually unlimited habitats: the whale will never fill up the entire ocean, the NMR will never use up all the available dirt, and the Mccaw will never fill up the entire sky, so there is perhaps no imminent danger of destroying their own niches as a result of becoming very long lived and, as a result, overpopulating themselves to death.
Most other species, though,
do have finite niche sizes, and so Josh Mittledorf would argue that senescence has been selected for to prevent niche destruction by overpopulation. Which raises the question of whether humans may owe their great longevity compared to their nearest relatives at least in part to the fact that they can migrate and occupy every conceivable environment, thus making their niche virtually unbounded as well — well, for the first million years or so, anyway. How this evolves is another question, but at least it’s food for thought.
Most examples of big longevity gains seem to be the result of disrupting default pro-aging processes, and the logic of limiting population sizes might explain the existence of at least some active pro-aging processes whose abrogation may be the easiest way forward to human applications. For more discussion,
see The Future of Aging.
Saturday, January 31, 2015 6:53 AM, “John M. “Johnny” Adams, GRG Exec Director” wrote: