The Geroscience Perspective

The authors of this article express a representative version of the geroscience perspective on aging research and its application in medicine. It is similar to that of the Longevity Dividend initiative of the past decade, which is to say that if a large amount of time and funding is invested, perhaps calorie restriction mimetic and similar marginally effective drugs can be brought to the clinic in order to modestly slow the progression of aging and add a few years of healthy life expectancy sometime prior to 2030. I believe I’m not the only one to be entirely underwhelmed by this strategy. This is not the future of aging research that we should either want or support.

Yes, it is a good thing that a sizable fraction of the research community is now prepared to work towards treating aging as a medical condition, and to advocate for that work in public. It wasn’t always this way, and it took considerable effort to bring about the present renaissance. Yet if the research community aims low, consuming funding and careers to make progress towards goals for human longevity that are only a tiny bit removed from doing nothing at all, what is the point? If we want to instead see meaningful progress towards rejuvenation therapies capable of achieving a far greater impact on aging and the health of older people, we should look to groups like the SENS Research Foundation and its allies in the research community, or the companies developing senolytic therapies to clear senescent cells. The goal should be to repair the causes of aging, aiming to put a stop to aging, to bring it under control, not merely slow it down a little.

Over the past decades, the compression of morbidity was a basic strategy in gerontology. This strategy is aimed at limiting morbidity to a short time period near the end of life, thereby reducing the burden of diseases and disabilities through delay in the age at onset of the most common aging-related pathological conditions. A few years ago, a new direction in geriatric medicine, geroscience, began to develop. This interdisciplinary field of research is aimed at understanding the mechanistic links between aging and aging-associated diseases and centered primarily on extension of healthspan. According to the “geroscience hypothesis”, aging could be manipulated in such a way that will in parallel allow delay the onset of all age-associated chronic disorders, because these pathologies share the same primary underlying risk factor, age.

Healthspan extension is a central component of activities aimed at achievement of ‘optimal longevity’, a condition defined as ‘living long, but with good health and quality of life’ including improved productivity, functioning and independence. Currently, the research attempted to enhance healthspan are focused primarily on slowing the biological processes underlying aging such as dysfunctions of mitochondria, impaired proteostasis and stem cell function and maintenance, deregulated sensing of cell energy status and growth pathways, cellular senescence, age-related decrease in stress resistance, as well as oxidative and inflammatory stress. These processes interact, influencing each other in order to maintain the normal pathways of cellular signaling and to support organismal homeostasis. The compensatory mechanisms mediating these processes, however, became exhausted when reaching a certain age and various aging aspects are manifested, enhancing as a consequence the risk of functional declines and progression of age-associated chronic pathologies.

Aging is traditionally regarded as ‘natural’ and consequently unpreventable process. However, in the opinion of many field experts, the idea that aging is inevitable part of human nature is rather questionable. Indeed, most present-day evolutionary theories postulate that aging has arisen as a by-product of fundamental evolutionary processes and does not have any specific function. If aging is in fact not an inadmissible component of life, then it might be manipulated like other processes that are commonly believed to be pathological or unnatural. The basic supposition underlying anti-aging research is that age-associated senescence may be regarded as a complex of pathophysiological processes that could be prevented, delayed, or even reversed.

The further elaboration of pharmaceuticals (both supplements and clinically approved drugs) specifically targeted at age-related pathologies is one of the most rapidly developing fields in modern biogerontology. An important point is, however, that most substances with potential anti-aging properties are apparently multifunctional and targeted at various molecular pathways that mediate aging. Furthermore, there is only limited evidence to demonstrate overall health benefits of using such substances so far. Findings from epidemiological studies reporting the long-term health impacts of these agents are rather inconsistent.

Another reasonable approach in anti-aging pharmacology is evaluation of the geroprotective potential of medications already approved by regulatory authorities for treating various pathological conditions related to aging. Among them, metformin, statins, beta-blockers, thiazolidinediones, newer generation β-adrenergic receptor inhibitors, renin-angiotensin-aldosterone system inhibitors, as well as anti-inflammatory medications appear to be the most promising drug candidates in this respect. The safety of these drugs has been confirmed in a number of clinical trials. This is also compelling evidence that they may improve health, well-being and physiological functioning in elderly patients suffering from chronic pathologies. One problem is that these substances are not used currently for treating age-related pathological conditions in the absence of clinical manifestations of particular illness. There are, however, good reasons to suggest that these agents could theoretically be redirected to preventing or treating other syndromes or conditions commonly associated with aging.

Despite an extraordinary rapid technological progress in pharmacology, there are few new preparations in the development pipeline now. Thereby, drugs generated on the basis of new knowledge gained from biogerontological research that can delay or prevent most age-associated disorders would apparently become “blockbusters” of modern pharmaceutical industry and market. That follows the idea that the extension of the healthy life expectancy by slowing aging process is the most efficient way to combat aging-related chronic illnesses and disabling conditions representing serious medical, social and economic issue in modern societies. This idea is referred to as the “longevity dividend” in the contemporary literature. Discovery and development of anti-aging drugs could likely provide an opportunity for revitalization of the drug development pipeline. Indeed, if it would be possible to slow down the aging process per se, then that would allow delay or prevent most aging-related disorders rather than combating them one by one, which is the conventional approach in the present-day disease-based paradigm of drug development.




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