A Good High Level Vision for Treating Aging Attached to an Unambitious Near Term Plan for Results

Not so long ago, the standard rhetoric on treating aging from the research establishment was silence. Talking in public about research indicating that aging could in principle be treated to extend healthy life was strongly discouraged, and was in fact a great way to harm your ability to raise funding and build a career in the field. That state of affairs continued for far too long, and held back progress as a result. Over the past fifteen years advocates within and outside the research community have brought about real change, however, and now many researchers talk about the prospects for slowing or reversing degenerative aging with no fear of repercussion. Indeed, anyone with a sense for these things should be able to see that the application of aging and longevity research is about to blossom into a massive, productive, and very energetic field of medicine: names will be made, and great deeds done.

At this stage in the process, things have advanced to the point at which we see bold statements of principle from researchers previously silent, but which are coupled to unambitious plans of action for the next few decades that are almost certainly doomed to produce marginal outcomes at best. The inertia of the research and development methodology that dominated the past fifty years guides researchers into drug development, aiming to alter the operation of metabolism in the late stages of aging, targeting processes that are very far removed from the actual causes of aging. You can't fix a worn engine by changing the oil, and you can't repair an age-damaged human by altering metabolism so as to slow down ongoing aging.

In some areas this doesn't matter because - fortunately - there are few steps between cause and end result, and the cause itself is something that can in principle be addressed via the drug development approach, or at least where the drugs are designed compounds with very precise modes of operation. Think of age-related macular degeneration caused by a buildup of metabolic waste compounds in retinal cells. Some mainstream researchers do end up working on the direct and most useful ways to break down those compounds rather than on some much more fanciful and much less helpful scheme of altering the metabolism of retinal cells to be more resistant to a later consequence of the damage process. In this case there are few steps between aggregation of waste and dysfunction, so less room for researchers to spend a lot of time and effort on investigating later stages in the condition. It still happens, but nowhere near as much as elsewhere in the aging process.

In most other relevant areas of medical research, however, attempts at building useful implementations of aging research are not yet moving in the right direction. So while we stand at a point at which earnest development could be underway on all aspects of rejuvenation biotechnology, the basis for treatments that can repair the damage that causes aging and thus restore health to the old, and prevent the development of age-related disease, for the most part the new rhetoric emerging from the research community steps over these opportunities. Plans for realizing rejuvenation treatments exist, but much of the research community remains bound to the old incremental roadmap of drugs and metabolic manipulation to attempt to produce marginal gain in the late stages of disease: that is what they know, where they can obtain grants, and where the gatekeepers and not going to challenge you just because you are doing something different. All inertia, and very slow to change.

So researchers these days are willing to set out bold goals to include the defeat of aging and elimination of age-related disease and decline, in principle at least, but at the detail level fall back to anemic plans that cannot possibly produce meaningful results any time soon:

Physiological geroscience: targeting function to increase healthspan and achieve optimal longevity

Most nations of the world are undergoing rapid and dramatic population aging, which presents great socio-economic challenges, as well as opportunities, for individuals, families, governments and societies. The prevailing biomedical strategy for reducing the healthcare impact of population aging has been "compression of morbidity" and, more recently, to increase healthspan, both of which seek to extend the healthy period of life and delay the development of chronic diseases and disability until a brief period at the end of life. Indeed, a recently established field within biological aging research, "Geroscience", is focused on healthspan extension. Superimposed on this background are new attitudes and demand for "optimal longevity" - living long, but with good health and quality of life.

A key obstacle to achieving optimal longevity is the progressive decline in physiological function that occurs with aging, which causes functional limitations (e.g., reduced mobility) and increases the risk of chronic diseases, disability and mortality. Current efforts to increase healthspan center on slowing the fundamental biological processes of aging such as inflammation/oxidative stress, increased senescence, mitochondrial dysfunction, impaired proteostasis and reduced stress resistance. We propose that optimization of physiological function throughout the lifespan should be a major emphasis of any contemporary biomedical policy addressing global aging. Effective strategies should delay, reduce or abolish reductions in function with aging (primary prevention) and/or improve function or slow further declines in older adults with already impaired function (secondary prevention).

Healthy lifestyle practices featuring regular physical activity and ideal energy intake/diet composition represent first-line function-preserving strategies, with pharmacological agents, including existing and new pharmaceuticals and novel "nutraceutical" compounds, serving as potential complementary approaches. Future research efforts should focus on defining the temporal patterns of functional declines with aging, identifying the underlying mechanisms and modulatory factors involved, and establishing the most effective lifestyle practices and pharmacological options for maintaining function. Continuing development of effective behavioral approaches for enhancing adherence to healthy aging practices in diverse populations, and ongoing analysis of the socio-economic costs and benefits of healthspan extension will be important supporting goals.

At least the principles are aimed high: getting that said out loud on a frequent basis by researchers in the field is half the battle. The rest of it is just a matter of pointing out that the prevalent implementation strategy is terrible in comparison to one based on repair of cellular and molecular damage, such as that proposed - in detail - in the SENS outline.


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