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The Near Horizon for Visions of Slowing Aging


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Posted 21 October 2014 - 11:48 PM


The mainstream of the aging research community, or at least that fraction of it that is interested at all in increasing healthy longevity by intervening in the aging process, is almost entirely focused on the use of drugs to alter metabolism to slightly slow the onset of frailty and ill-health in later life. There isn't even much effort to find new drugs: candidates are largely existing drugs. Many of these researchers exclusively discuss compression of morbidity, the goal of extending healthy life without extending overall life span. There is still an aversion in many circles to any talk of extending overall human life spans, no matter how realistic the prospects, and the boundaries of the possible for these folk stops at slowing aging modestly. These are researchers who look ahead to another twenty years of research and development that looks exactly like the last fifty: a slow mining of the natural world in search of compounds that can be used as drugs to alter the operation of the human body to produce marginal benefits. No revolution, no great advances, just a continuation of the present trends.
This is an exceedingly narrow horizon, a box even. These researchers believe it will be challenging and expensive and slow to generate benefits, and if standard issue drug development after the 1970s model that is still with us today is all they plan to do, then that seems about right. Despite great advances in biotechnology, the research community is still only in the initial stages of of mapping the complexities of metabolism, epigenetics, and their changes with aging. There is little in the way of a clear path forward to actually slow aging in humans, and where there are potentially promising areas of study, such as calorie restriction, large amounts of funding and time have so far failed to produce meaningfully beneficial therapies based on calorie restriction mimetics.
This dismal situation is why we need a disruption of the entire field in favor of research approaches that might actually work to greatly extend healthy and overall human life, that have much more in the way of straightforward and defined research plans leading to therapies, and wherein the scientists involved are not afraid to stand up and state that the end of frailty and disease in aging, indeed the end of aging itself, is the goal. The present mainstream is not getting the job done: their primary focus is on gaining knowledge of metabolism and the fine details of aging, not of taking all that is known so far and building the best therapies possible.
The Strategies for Engineered Negligible Senescence (SENS) approach typifies the sort of reaction to the mainstream you'll find among more visionary researchers who see that much more can be done about aging in the near future. There are much better paths to a future of longer lives than the tired road of drug development. If all that happens over the next twenty years is more messing with metabolism in the vague hope that small and expensive benefits will be realized, than that will be a waste of a great opportunity. Enough is known to make real progress in treatments for aging today - the only thing missing is large-scale funding and widespread public support.
The open access paper quoted below provides a very clear and detailed look at the viewpoint of those who think that only marginal gains are possible, and that researchers shouldn't talk about or try to achieve extension of overall human life span. You should compare it with a reading of the introduction to the SENS research program. On the one hand a manifesto that has as an important strand of work digging through existing drugs in search of something, anything, that might do more good than harm. On the other, a call for taking the best of present knowledge to deliberately target the known root causes of aging with the aim of turning back the progression towards disability and disease. Night and day.
Translational Geroscience: Emphasizing function to achieve optimal longevity

Investigators working in fields related to the biology and biomedicine of aging ("Geroscientists") are among those at the forefront for creating solutions to the impending impact of global aging. Several strategies have been identified, the most well-known of which is the "compression of morbidity" paradigm advanced by Fries over 30 years ago. This approach is based on the idea that because most illness today is in the form of chronic diseases, if the onset of these disorders can be delayed to an older age, and the delay is greater than any associated increase in life expectancy, then illness, disability and their sequelae can be restricted to a shorter period at the end of life.
The key issue is how to best achieve compression of morbidity. Presently there is considerable support for the tactical approach of slowing the fundamental biological processes of aging, as opposed to treating (or even preventing) individual chronic diseases. Much of the momentum for this approach has been created by the tremendous advances made over the last 25 years in what is now the routine manipulation of lifespan in model systems such as Drosophila or C. elegans. The idea is that targeting specific 'upstream' pathways, originally identified in model systems, holds promise for delaying the age of onset of multiple age-associated comorbidities as a group, whereas delaying the clinical manifestation of a particular disease may simply result in some other age-related disorder "backfilling" the consequent reduction in risk. Slowing aging at the molecular and cellular levels would, theoretically, increase "healthspan", i.e., the period of life free from serious chronic diseases and disability, thus compressing morbidity and facilitating attainment of optimal longevity.
In the area of promising dietary and pharmacological strategies, the National Institute on Aging (NIA) Interventions Testing Program (ITP) has become a highly successful source of potential treatments to reduce age-associated pathologies and extend lifespan in mice. Moreover, independent laboratories working in basic aging biology recently have produced a remarkable number of potential targets and associated target-modulating treatments worthy of translational consideration. Overall, it seems likely that identification of candidate therapies from preclinical models will not be the major limitation for establishing effective interventions to slow the effects of aging and delay the onset of age-associated co-morbidities.
One of the main obstacles for translation of treatments to improve function with aging lies in the initial steps from assessments in animal models to testing for safety and efficacy in human subjects (phase I and II clinical trials). The process for bringing new prescription agents targeting aging to market has been described in detail by Kirkland, and the steps, time lines and costs involved are extensive. However, development of drugs for older patients with geriatric syndromes such as frailty, as well as clinical disorders that are antecedents of these syndromes, clearly is an important goal and area of interest for the pharmaceutical industry.
Complementary options to new proprietary prescription drug development also exist, and may represent, in some cases, a nearer-term source for new therapies with function-enhancing effects for older adults. For example, widely used FDA approved drugs with established safety and efficacy for treating age-associated clinical disorders such as cardio-metabolic diseases (e.g., metformin, statins, renin-angiotensin system inhibitors, recent generation beta-blockers) could undergo repurposing for treatment of at risk older adults or patients with aging syndromes. Although such agents could be prescribed presently for their off-label effects in cases in which the existing evidence supports likely efficacy, broad use of these drugs likely will require new trials with appropriate subject groups and clinical endpoints recognized by drug regulatory authorities.

 
On the one hand it is good that ever more of the research community and its supporters are waking up to the idea of treating aging and speaking in public on that topic, rather continue with the past course of patching its consequences in silence. On the other hand, the specific research and development strategies advocated by most factions are just not good at all. They will produce knowledge, certainly, but nothing in the way of treatments that might be expected to add even a decade to human life spans. We can and should do far better than this, and the way to do so is via SENS and other repair-based approaches to the damage of aging. Only repair can lead to a future of actual rejuvenation and the prospect of unlimited healthy life spans.

View the full article at FightAging


Edited by niner, 22 October 2014 - 11:40 AM.





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