It isn't entirely fair to categorize geroscience as the worse of the two serious and considered approaches to the treatment of aging as a medical condition, the one that isn't as good as the SENS methodology of rejuvenation through repair of molecular damage. Nor is it entirely the case that geroscience aims only to modestly slow aging to gain a few years while SENS aims at radical life extension and rejuvenation of the old. It is also inaccurate to say that geroscience is concerned only with calorie restriction mimetics and other ways to induce beneficial stress responses, the manipulation of metabolism to resist aging a little better without addressing its root causes.
Yet if you pick a random point in the SENS portfolio and a random point in the geroscience portfolio, the stereotypes above are what you'll likely land upon. Unless, of course, you happened to touch on some portion of the growing interest in senolytics, the selective destruction of senescent cells. This is the major area of overlap between the two at the present time, or - if you choose to look at things the way I do - the most prominent example of the way in which SENS will eventually take over the mainstream of research because it is demonstrably more effective. Senolytics has become a focus for an increasing fraction of the research community as the positive data continues to roll in, and justifiably so. Larger, more reliable effects are what is desired by everyone. Sadly it remains the case that most researchers and sources of funding still need to be persuaded to put aside their geroscience work in favor of the better SENS approach.
The S. Jay Olshansky article I noted a few days back is one of a few interesting position papers from a recent edition of the Journal of the American Medical Association focused on geroscience as an endeavor. The other two are noted below, and each is worth reading as a standalone piece. The bigger picture is that the tenor of the great cultural conversation about aging is changing, has changed significantly, is no longer what it was even a decade ago. The technologies that slow and reverse aging are starting to emerge and be demonstrated in ways that cannot be refuted. Treating aging as a medical condition is no longer mocked in the media - the serious people are convinced. The future is arriving.
Chronic health problems related to the unprecedented aging of the human population in the 21st century threaten to disrupt economies and degrade the quality of later life throughout the developed world. Fortunately, research has shown that fundamental aging processes can be targeted by nutritional, genetic, and pharmacologic interventions to enhance and extend both health and longevity in experimental animal models. These findings clearly demonstrate that the biological rate of aging can be slowed.
The geroscience hypothesis, for which there is abundant evidence in animal models, links these biological discoveries to human health by proposing that targeting biological aging processes will prevent, or at a minimum delay, the onset and progression of multiple chronic diseases and debilities that are typically observed in older adults. For example, interventions that extend the life span of mice often also prevent or slow the progress of several types of cancer, reduce atherosclerotic lesions, improve heart function, alleviate normal age-related cognitive loss, and even improve vaccine response.
One of the main geroscience accomplishments is to highlight a small number of major "pillars," interacting molecular and physiological processes that underlie the biology of aging, for instance, metabolism, proteostasis, macromolecular damage, inflammation, adaptation to stress, epigenetics, and stem cells and their regeneration. The key feature of this conceptual framework is that these processes are understood to be tightly interrelated. These findings have emerged from the remarkable progress made in recent years in dissecting aging processes in model organisms. The discovery of cellular and molecular pathways that modulate healthy aging in diverse species across great evolutionary distances offers an unprecedented opportunity for intervention
Age is the leading predictive factor for most of the chronic diseases that account for the majority of morbidity, hospitalizations, health costs, and mortality worldwide. The fundamental aging processes that contribute to phenotypes characteristic of advanced old age, such as muscle weakness and loss of subcutaneous fat, also appear to underlie the major chronic diseases, geriatric syndromes, and loss of physical resilience. These aging processes can be broadly classified as follows: (1) chronic, low-grade inflammation that is "sterile" (occurring in the absence of known pathogens), together with fibrosis; (2) macromolecular and cell organelle dysfunction (such as DNA damage, dysfunctional telomeres, protein aggregation and misfolding, decreased removal of damaged proteins, or mitochondrial dysfunction); (3) changes in stem cells and progenitors that lead to reduced capacity to repair or replace tissues; and (4) cellular senescence.
Senescence involves essentially irreversible arrest of cell proliferation, increased protein production, resistance to programmed cell death (apoptosis), and altered metabolic activity. Senescent cells accumulate in multiple tissues as a result of chronological aging, especially after middle age, and in tissues central to the pathogenesis of chronic diseases. For example, senescent cells accumulate in and near bone in patients with age-related osteoporosis and in blood vessel walls in patients with vascular disease.
Some senescent cells develop a senescence-associated secretory phenotype (SASP) that entails release of proteins, bioactive lipids, nucleotides, extracellular vesicles, and other factors. The SASP contributes to inflammation and the breakdown of tissues, stem and progenitor cell dysfunction, and the spread of senescence to nonsenescent cells. The SASP, immune cells attracted and activated by the SASP, and spread of senescence contribute to profound local and systemic effects with even small numbers of senescent cells. For example, transplanting small numbers of senescent cells around knee joints in young mice leads to joint pain and pathologic changes closely resembling human osteoarthritis. Transplanting senescent cells into middle-aged mice so that only 1 in 10,000 cells in the recipients is a transplanted senescent cell is sufficient to cause profound physical dysfunction within 2 months, together with early death due to accelerated onset of age-related diseases as a group, compared with transplanting nonsenescent cells.