Senescent Cells: A Key to Anti-Aging and Age Related Diseases

Source: https://www.flickr.com/photos/glyn_nelson/24766804066

Source: https://www.flickr.com/photos/glyn_nelson/24766804066

For many who are unfamiliar with the anti-aging field, their first thoughts when they hear the term anti-aging may be something along the lines of reduced skin wrinkles or increased hair growth; a means to alleviate superficial aging. However, take one look in, and you will realize that anti-aging encompasses a far wider and deeper approach to cure age related diseases and increase healthy lifespan [4]. As people age, the potential for disease and degradation of tissues increases exponentially [1]. Anti-aging researchers explore means to interfere with the progressive degeneration of the human body: the inevitable process of aging. Tim Peterson, head of the Genomics and Metabolomics in Aging and Mental Health Lab at the Medical School in Washington University in St. Louis, describes the anti-aging field having “a big fixation on dramatic effects and substantial treatments for age-related diseases and healthspan”. The key word here is healthspan: not the elongation of life regardless of the condition of the body, but the elongation of time that can be spent in health. Time and time again, many inside and outside of the scientific community have pondered if there indeed is a miracle elixir that can reverse the devastation time often leaves in its wake. But at present, the focus of many researchers in anti-aging has shifted, not to reverse the damage carried out by time, but to remove the damage altogether.

The idea, put in the simplest terms, is this: remove the damage caused by age to hinder age related disease and thus lengthen healthy lifespan. It seems a logical solution, but until a few years back, no one really understood what, if any, specific type of cells or particular proteins were mainly causing age related diseases or degenerations. Jan van Deursen et al., leading researchers in the anti aging field, discovered that a non-dividing cell type, senescent cells, were one of the key players in the aging pathway, revitalizing a decades old notion first formulated by microbiologists Leonard Hayflick and Paul Moorhead [2]. Senescent cells are a category of cells that have ceased division but have failed to undergo apoptosis, or regulated cell death. They remain in their respective tissues and, not unlike cancer cells, continue to constantly “evolve and diversify” [3]. Intriguingly, senescence was actually originally known to be a preventative process, a “cellular stress response” against cancer-causing DNA damage to insure affected cells would not undergo tumorigenesis [3] [1]. This is still the case, but currently these senescent cells are construed to have peculiar defining characteristics that can be both advantageous and detrimental.

Senescent cells secrete many types of proteins and enzymes that contribute to inflammatory effects and overall “local and systemic dysfunction and disease” in the particular tissue they are located in [4]. At the same time, these secretions may be signaling to the immune system that senescent cells present in the tissue must be removed. However, as the body ages, its senescent cell removal mechanisms may become faulty and slow. At the same time cell secretions may be warning the immune system, the very secretions may be creating a myriad of favorable conditions in a “tissue microenvironment” for tumor cells to thrive. In fact, this is likely one of the main reasons why older people, with increased senescent cells compared to younger generations, are more likely to get cancer [1]. The exact processes for many of these deleterious effects of senescent cells is not yet fully understood, but it is almost certain that removal of these cell accumulations can produce profound benefits to aging tissues and perhaps even provide therapeutic approaches to age-related diseases.

For the past few years, researchers have been producing progeroid mice having sped-up aging processes to efficiently test whether removal of senescent cells can lead to positive impacts on the adverse effects of age or age related diseases. In 2014, van Deursen wrote that therapeutic approaches to senescence is “a nascent yet promising area of investigation” [3]. Now, van Deursen, as founder of Unity Biotechnology, and Mayo Clinic have begun human clinical trials of a class of drugs commonly known as senolytics that have been designated as the exterminators of senescent cells [2]. If successful, these senolytics could treat people with diseases like osteoarthritis, atherosclerosis, macular degeneration, pulmonary insufficiency, renal failure, and even neurodegeneration: all conditions that can accompany age and an accumulation of senescent cells [2] [1].  So far from experiments with progeroid mice models, significant defense against age-related deterioration could be seen with senolytics that include dasatinib and quercetin, where the combination of the two can “selectively target a broader range of senescent cell types than either agent alone” [4]. In an experiment conducted with non-progeric mice, removal of senescent cells showed an extended median lifespan of mice by an impressive 25% [2]. Besides the effects of anti-aging, senolytics also have many practical features. Because senescent cells don’t proliferate aggressively like cancerous cells, there is no need to clear the tissue of all senescent cells, and senolytics need to be used only for a relatively short duration of time. This is physiologically and psychologically more advantageous than other relentless cycles of drugs. In theory, the senolytic needs to be administered “say once per year”, which can help dampen any damaging side effects as well [2] [1].

Many researchers, like Peterson who expresses that “removal of senescent cells is definitely a promising approach”, are hopeful about the removal of senescent cells to combat aging. However, it seems that the opinion is fairly divided on the effectiveness of senolytics to carry out this removal. Peterson, although forward-looking on removal of senescent cells, adds that “it would be extremely difficult to find a magic bullet” that could effectively encompass any one, let alone most, age-related diseases or processes into a simple miracle cure. He makes a legitimate point of concern regarding senescent cells: although cells can be classified as senescent, currently, there are no specific markers to pinpoint all types of senescent cells, making them difficult to discern and remove when they are dispersed throughout different tissues [1]. He also points out an interesting factor that many might not consider, that “No one healthy that I would know of would want to be on any drugs like senolytics that deal with cancer pathways because these drugs target very important processes. It’s pretty hard medication. It’s not like vitamins where people can be casual users”. Like many transformative drugs, there are numerous pitfalls and obstructions to making senolytics effective, reliable, and safe for use. Nonetheless there is substantial evidence for the potential eradication of senescent cells in tissues in living organisms. Now we must wait and watch, while researchers do their work to make effective senolytics that could possibly one day allow all to live full, healthy lifespans free of age related disease and degeneration.

Edited by: Eric Song




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