Longevity Versus Frailty

In the most simplistic view, aging is little more than a matter of damage accumulation. The more damage you have, the worse your health, and eventually it kills you. At a very high level, this is in fact the way things are, but living organisms are extremely complex systems, and "damage" is made up of numerous primary causes, direct results of the normal operation of cellular metabolism. These spiral out into hundreds or thousands of secondary and later consequences: further damage, evolved reactions to damage, and so forth. The middle portion of the intricate web of biochemistry that links damage at one side to specific age-related diseases at the other is still comparatively poorly mapped, precisely because it is hugely complex. It is also surprisingly variable from individual to individual, for all that the basic root causes of aging are comparatively simple processes that occur in the same way for everyone.

Thus our situation is that frailty in aging is inevitable in the long run for any individual managing to somehow evade all of the late stage system failures of aging that kill without frailty, but over the present median human life span many people do avoid becoming frail before succumbing to those other ends. So there is some distinction between processes of aging and processes of frailty, for all that the latter is absolutely a function of the former. You might consider this to tie back into the fact that genetic differences have little effect on mortality and health until later in life. The effect of genetic variations on longevity is to a first approximation a matter of how your system manages to cope with being damaged.

Over the next few decades a great deal of effort will be devoted to understanding how exactly all of this works - mapping the middle of the linkage between damage and end results. This is effort that I hope to see side-stepped and evaded via the approach of repairing this fundamental damage, thus creating a toolkit of first generation rejuvenation therapies. How human biology reacts to being very damaged by the causes of aging is a field of research that I would like to live to see become an academic curiosity, along the lines of how human biology reacts to smallpox - something of interest, but neither vital nor important, because it will no longer be the case that people suffer in that state. We have the opportunity to make this happen in the years ahead, but that very much requires greater support and funding for SENS and similar lines of rejuvenation research.

Older people are at risk of developing frailty with advancing age. The prevalence of frailty increases from 2.5-3% in adults aged 65 years to 30-35% in those older than 85 years. These results suggest that an association exists between longevity and frailty. However, at the same time, even at advanced age, the majority of older adults are free of frailty, suggesting that factors different from those contributing to or produced by the life length are involved in producing frailty.

Genetic and epigenetic factors, nutrient-sensing systems, mainly the so-called insulin/insulin-like growth factor-1 signaling pathway, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, inflammation, and some hormonal systems are involved in longevity. However, factors involved in frailty are mainly inflammation and hormones, with an anecdotal role for genetic and other potential factors, but even these two common factors seem to regulate longevity and frailty in different ways. Moreover, their effect on frailty seems to change when they are acting in combination.

Link: http://www.karger.com/?DOI=10.1159/000382057

Comments

Reason, Are there any approved treatment for other medical conditions that work in the way we want SENS treatments to work? As in, treatments for something we don't know almost everything about and how it all works, with still so many unknowns. It would be great to treat aging this way, if we could just simply repair the damage without understanding all the metabolic processes involved, but that approach is something that many scientists seem to dismiss as not real science. I think that view is slowly changing, but not fast enough.

Posted by: Ham at October 30th, 2015 5:31 AM

A tremendous boost to aging research would be the formal recognition of aging as a treatable disease. Apparently, today is the last day to post your comments to WHO to encourage them to support this stance. Sorry for the last minute notification but I just became aware of this. The discussion is over at http://www.kurzweilai.net forums with suggested ideas that you can simply cut and paste at the WHO website. http://www.kurzweilai.net/forums/topic/the-most-important-2-minutes-of-this-decade-what-to-do-now-to-cure-aging
The WHO link (also posted in the thread) is http://www.who.int/ageing/consultation/en
You can just click on one of the links at the bottom and comment.

Posted by: Morpheus at October 30th, 2015 1:01 PM

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