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For today, a post wherein I reproduce part of an exchange from the GRG mailing list. Robert Bradbury (who has some interesting ideas on aging that you might want to read) is presently in an optimistic frame of mind based on a look back at the past decade:
Some of you may want to do a PubMed search on: genes AND aging. It now turns up more than 5600 articles. That would have been a *much* smaller number in the mid-to-late '90s.
Of particular interest on the first page are the articles by C. Kenyon reporting on aging genes in C. elegans, S.M. Jazwinski on aging in yeast, J. Campisi on cell senescence and cancer and D.C. Wallace on the involvement of mitochondrial mutations in somatic cell aging.
These are all some of the leading researchers in aging studies.
The article by C. Kenyon is particularly important as they used an RNAi library to identify 23 new longevity genes in C. elegans.
Given the recent transgenic mouse studies extending the lifespan by using retargeted catalase (Rabinovitch) and the Klotho study (Kuro-o) it seems likely that transgenic mouse studies of longevity will increase significantly. But transgenic mouse studies are long and expensive (though there appear to have been tens of thousands of them which have been done). Now that the Zebrafish [genome] map is essentially complete it is possible to use them as a vertebrate model for aging. Though they live longer than mice it is much cheaper to create transgenics in a wide variety of genes (many more eggs at very low cost) and study internal physiological changes that take place with age (they are transparent). There are also very low costs for keeping thousands of them which is something not usually done with transgenic mice.
These things combined lead me to the conclusion that we are entering the "golden age" for understanding aging. By 2010 we should have a fairly good understanding of all of the significant causes of aging and by 2015 have probably developed a number of interventions for human beings to be tested in human beings.
One of the debates will revolve around whether those interventions should be transgenic manipulation of cells (either in vivo or using stem cells) or whether they will be through drug companies providing drugs.
So the chances of anyone aged 55 or younger of having a significantly extended lifespan over the current average lifespan seems quite high in my opinion.
He is right in that the basic research is moving forward very nicely, but I'm a little less optimistic at the moment. This is partially a result of my libertarian concerns regarding regulation and partially a result of where I see the research funding going at the present time:
The thing that bothers me is that I see all the presently engaged money sliding down the slope to the "slow aging" end. The range of plausibles down there - metabolic tinkering, lifelong gene alterations, etc - don't appear to include interventions that will do much good for us folks who used up 2/3 or more of our damage quota by the time they're introduced.
We need, ASAP, significant resources heading upslope to SENS-like strategies aimed at reversing the damage of aging. If by 2020 the best that's available is along the lines of super-[calorie restriction] or super-Klotho in humans that will produce 30% life span extensions for those who benefitted from them for an entire life, I fear we oldtimers will be out of luck.
I make the same cautions a little more clearly in the latest Longevity Meme newsletter:
There is no such thing as useless information in cellular biochemistry, but practical anti-aging medicine for those of us who have burned through two-thirds or more of our life already will probably not come from comparatively modest tweaks - genetic or otherwise - to metabolic processes. All these do is slow the rate at which age-related damage accumulates, something that decreases in utility the later in our lives it starts.
I don't see it as implausible that longevity science could vanish down the rabbit hole of producing a better calorie restriction or a better klotho - something that would be wonderful and effective for people with their whole life ahead of them, but singularly useless for those of us reading this today. It's up to us to ensure that this does not happen: the time to influence the directions and emphasis of longevity research is now, just as it always has been. You can have your say in the matter by donating to the rejuvenation (or late intervention) component of the Mprize, which rewards scientists who work on anti-aging science specifically designed to save the lives of the aged. If we fail, we'll be left looking just like the last generation of healthy life extension supporters and advocates - and that would not be a good thing, not at all.
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Posted by Reason
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