Contributed by: Annabelle Hutchinson
Cellular Senescence and Aging: Can We Turn Back the Clock?
Cellular senescence is a biological process in which cells lose their ability to divide and function correctly. It’s an intrinsic component of aging and has been associated with numerous age-related diseases, including Alzheimer’s disease, atherosclerosis, osteoarthritis, and Parkinson’s disease. Scientists are currently developing therapies to target senescent cells and ‘turn back the clock’ in human aging to slow the effects of aging.
Cellular senescence was first discovered in the 1960s by biologists Leonard Hayflick. They noticed that normal human cells could only divide about fifty times before stopping. Beyond this limit, cells enter a state of “senescence” where they are still alive but no longer proliferate. Every time a cell splits, its telomeres – protective caps on the ends of chromosomes – shorten. Research shows that telomeric shortening and cellular senescence can lead to chronic inflammation, tissue dysfunction, and age-related disease.
Senescent cells exhibit changes in gene expression, protein production, metabolism, and physical structure. Importantly, they secrete a distinctive array of molecules called the Senescence-Associated Secretory Phenotype (SASP), which includes inflammatory cytokines, growth factors, and proteases. The SASP can influence surrounding cells and the immune system, often promoting chronic inflammation, tissue dysfunction, and the progression of aging and age-related diseases, including neurodegeneration and sarcopenia (muscle degeneration).
Senescent cells in our tissues accumulate as we age, and their presence has been linked to a variety of age-related conditions. Senescent cells contribute to the aging process and the development of these diseases by disrupting tissue function and structure, promoting chronic inflammation through the SASP, and impeding stem cell function.
However, senescence is biologically useful in many ways. In mouse models, tumor growth is dramatically increased when cells are modified to eliminate senescence. So, in terms of cancer, senescence plays a vital role. You do not want cancerous cells endlessly dividing and growing. If you target senescent cells after they become senescent, however, you can reproduce the positive effects of “youth” without increasing cancer risk.
Turning Back the Clock?
The accumulating evidence linking cellular senescence with aging and age-related diseases has led to a surge of interest in interventions that target senescent cells to improve health and extend lifespan. Judy Campisi and Jan Van Deursen have both targeted senescent cells in mice through genetic manipulation and seen impressive results in terms of lifespan and age-related disease. This research proved very exciting for those interested in longevity. This excitement gave rise ‘senotherapeutics’, which includes (1) senolytics, which are drugs that selectively kill senescent cells, and (2) senomorphics, which are drugs delay and reverse senescence.
In animal models, senotherapeutics have shown promise in alleviating symptoms of age-related diseases and extending healthspan, the portion of life spent in good health. In mouse models like the ones performed by Campisi and Van Deursen, clearing senescent cells improved cardiac function, enhanced insulin sensitivity, and increased lifespan.
While the initial results from senotherapeutics are promising, many questions remain. What is the long-term safety of these interventions? What is the optimal timing and frequency of treatment? Will these findings in animal models translate to humans? How will we navigate the ethical, social, and regulatory implications of therapies aimed at extending human lifespan?
The complex interplay between cellular senescence and aging offers exciting opportunities for interventions that could extend healthspan and lifespan. While we are not yet able to ‘turn back the clock’ on aging, the rapid advances in our understanding of cellular senescence give reason to be optimistic about the future. The research in this field could potentially transform our approach to aging, shifting from treatment of individual age-related diseases to targeting their common root cause: cellular senescence.