Folklore surrounding the hunt for the fountain of youth. The subject of numerous urban legends. No matter the country, era, or generation, it seems that people are preoccupied with maintaining their best health and frequently have the wish to live forever. But it goes without saying that everyone passes away. The fact that modern humans have one of the lowest average life spans in history only serves to make problems worse. Despite the fact that technology is still advancing exponentially and that new discoveries are expanding human lifespans, Science aims to change that with senolytics by actively reversing the aging process rather than just preventing or treating diseases.
Senescence: A cell state
That was discovered in the mid-1900s. It refers to the stage in a cell cycle where it no longer divides but remains metabolically active, producing a variety of molecules depending on what type of cell it originally was since almost all cells have the ability to become senescent. These molecules include cytokines, growth factors, proteases, etc. ultimately with the end goal of stimulating the immune system to destroy them. With aging and immunosuppression, cells tend to go into senescence more than the body is capable of eliminating them, ultimately contributing to different disease processes in the body. Research in senolytics, drugs that destroy senescent cells, show significant change in different age-related morbidities with successful clinical trials in mice.
Secondary Source: Scientific American: To Stay Young, Kill Zombie Cells (Scudellari, 2017)
Scientific American calls them zombie cells and maybe appropriately so. They represent a state of "undead" similar to the fictional Halloween creature. Senescence referring to the non-functional, non-essential cells that accumulate over time. The many types of cells and the number in which they accumulate apparently not only take up space in the human body but actually contribute to disease processes just by existing. Elimination of such cells proved that their age-sensitive organs could be restored to their previous functioning capacity. In early 2017 alone, animal studies confirmed that senolytics can contribute to fitness, fur growth and even kidney function. A different study in 2016 also showed it can increase the lifespan of normally ageing mice by up to 25%.
The potential of senescent cells
Jennifer Ellissef, a biomedical engineer of John Hopkins Unviersity stated that removing senescent cells could stimulate new tissue production. This could be the gamechanger with age-related diseases as the problem of absent growth or activity is sometimes even more detrimental to health than diseases causing it. Unity Biotechnology of San Francisco, California reports that because of such, senolytics would prove beneficial to patients with osteoarthritis, eye diseases like macular degeneration and some pulmonary diseases.
Current challenges in senolytics research
While animal models and testing have been rather successful, there is still a lot to be learned about senolytics. One of the major roadblocks is that the USFDA does not consider ageing a condition in need of treatment so studies have yet to be thorough and confirmatory enough to allow human trials and sometimes even further testing with animals. Since almost all cells are capable of entering senescence, the absence of universal features also makes it difficult to narrow down the therapeutics exactly. As of this writing, there are 14 senolytics under study.
Primary Source: Cellular Science: A Translational Perspective (Kirkland and Tchkonia, 2017)
Cellular senescence is scientifically described as a cell that is in a state of essentially irreversible replicative arrest. Plainly speaking, it is a cell that no longer divides. Over time such cells accumulate in tissues especially those prone to the negative effects of aging such as the heart and kidneys and since these cells also tend to be pro-inflammatory but apoptopically resistant, they contribute to the overall disease process. These cells also produce the tissue destructive molecule called SASP which stands for senescence-associated secretory phenotype which are the major contributors to the senescence-related inflammation, dysfunction of metabolism and stem cell function as well as other geriatric conditions by secreting cytokines, bradykines. This state of chronic inflammation is often a progenitor of age-related disease like osteoarthritis. Animal studies showed that mice that were transplanted with minimal senescent cells produced significant osteoarthritis while the removal of them via drug administration activated apoptosis, clearing the mice of these cells and alleviating the symptoms.
The effect of senescent cells and the SASPs they prouduc vary from cell type to cell type, what stimulated them to enter senescence and the presence of drugs such as metformin, steroids, etc. These only go to show that there are a vast array of opportunities in which senolytics could not only possibly extend life span but cure diseases as well.
Works Cited
Scudellari, M. (2017). To stay young, kill zombie cells. Nature News, 550(7677), 448. http://www.nature.com/doifinder/10.1038/550448a
Kirkland, J. L., & Tchkonia, T. (2017). Cellular Senescence: A Translational Perspective. EBioMedicine. http://www.sciencedirect.com/science/article/pii/S2352396417301548
Marchetti, Gina. “Two Stage Sisters: The Blossoming of a Revolutionary Aesthetic.” Jump Cut 34 (1989): 95-106.
Zhang, Yingjin. Chinese national cinema. Routledge, 2004.
