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Senescent Cells and Senolytics


As your body ages, increasing amounts of your cells enter into a state of senescence. Senescent cells do not divide or support the tissues of which they are part; instead, they emit a range of potentially harmful chemical signals that encourage nearby cells to enter the same senescent state.

Their presence causes many problems: they degrade tissue function, increase levels of chronic inflammation, and can even eventually raise the risk of cancer. Today, we will talk about what senescent cells are, how they contribute to age-related diseases, and, perhaps most importantly, what science is hoping to do about the problem.

Senescent cells and aging

Senescent cells normally destroy themselves via a programmed process called apoptosis, and they are also removed by the immune system; however, the immune system weakens with age, and increasing numbers of these senescent cells escape this process and build up.

By the time people reach old age, significant numbers of these senescent cells have accumulated in the body, causing inflammation and damage to surrounding cells and tissue. These senescent cells are one of the hallmarks of aging and a key process in the progression of aging [1, 2].

A new class of drugs known as senolytics focuses on the destruction of these stubborn “death-resistant” cells from the body in order to reduce inflammation and improve tissue function. New research proposes to remove some of these senescent cells in order to promote healthy longevity.

Here, we have LEAF writer and biologist Victor Bjoerk giving a short talk about senescent cells and their consequences.

A brief history of senolytics

The health and lifespan of mice have been demonstrated to improve by the removal of senescent cells using a transgenic suicide gene [3], and additional experiments showed that the same could be achieved using small molecules.

Senescent cells comprise a small number of total cells in the body, but they secrete pro-inflammatory cytokines, chemokines, and extracellular matrix proteases, which, together, form the senescence-associated secretory phenotype, or SASP. The SASP is thought to significantly contribute to aging [4] and cancer [5]; thus, senolytics and the removal of the SASP are a potential strategy for promoting health and longevity.

It was discovered through transcript analysis that senescent cells have increased expression of pro-survival genes consistent with their resistance to apoptosis [6]. Drugs targeting these pro-survival factors selectively killed senescent cells. Two such drugs were dasatinib and quercetin, which were both able to remove senescent cells but were better in different tissue types.

However, it was discovered that a combination of the two drugs formed a synergy that was significantly more effective at removing some senescent cell types [7].

In other studies, removing only thirty percent of senescent cells was sufficient to slow down age-related decline. These results suggest the feasibility of selectively ablating senescent cells and the efficacy of senolytics in alleviating the diseases of aging and promoting healthy longevity [8, 9, 10].

Further confirming the potential of senolytics to treat age-related disease, a recent study demonstrated the benefits of senolytics for certain aspects of vascular aging [11]. This was the first study to show that clearance of senescent cells improves aspects of vascular aging and chronic hypercholesterolemia, thus making senolytics a possible viable method of reducing morbidity and mortality from cardiovascular diseases.

Even more recently, progress has been made in treating atherosclerosis using senolytics to address the “foam cells” that contribute to this disease [12]. There has also been progress in ways to treat type 2 diabetes using senescent cell removal [13]. Senolytics also have the potential for slowing skin aging [14] and treating osteoarthritis [15].

Senescent cells, however, are not all bad, and evidence shows that they play a role in cellular reprogramming [16] and wound healing. Like all things in biology, it is therefore clearly a question of balance: too much clearance of senescent cells would be bad for wound healing and cellular reprogramming, but too many senescent cells lead to damage [17, 18].

Therefore, the key to developing effective senolytic therapies that combat the diseases of aging is the creation of even more accurate biomarkers to measure senescent cell numbers in tissue [19] combined with effective delivery methods for the selective removal of senescent cells.


There are now several companies involved in researching and developing senolytic therapies, and with Unity Biotechnology moving to clinical trials in 2018 and others close behind, it seems likely that senescent cell clearance will be the first repair-based rejuvenation therapy to arrive.


[1] López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.

[2] van Deursen, J. M. (2014). The role of senescent cells in ageing. Nature, 509(7501), 439-446.

[3] Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., Van De Sluis, B., … & van Deursen, J. M. (2011). Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature, 479(7372), 232-236.

[4] Freund, A., Orjalo, A. V., Desprez, P. Y., & Campisi, J. (2010). Inflammatory networks during cellular senescence: causes and consequences. Trends in molecular medicine, 16(5), 238-246.

[5] Coppé, J. P., Desprez, P. Y., Krtolica, A., & Campisi, J. (2010). The senescence-associated secretory phenotype: the dark side of tumor suppression. Annual review of pathology, 5, 99.

[6] Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., … & O’Hara, S. P. (2015). The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging cell, 14(4), 644-658.

[7] Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., … & O’Hara, S. P. (2015). The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging cell, 14(4), 644-658.

[8] Tchkonia, T., Zhu, Y., Van Deursen, J., Campisi, J., & Kirkland, J. L. (2013). Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. The Journal of clinical investigation, 123(3), 966-972.

[9] Zhu, Y., Armstrong, J. L., Tchkonia, T., & Kirkland, J. L. (2014). Cellular senescence and the senescent secretory phenotype in age-related chronic diseases. Current Opinion in Clinical Nutrition & Metabolic Care, 17(4), 324-328.

[10] Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., … & O’Hara, S. P. (2015). The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging cell, 14(4), 644-658.

[11] Roos, C. M., Zhang, B., Palmer, A. K., Ogrodnik, M. B., Pirtskhalava, T., Thalji, N. M., … & Zhu, Y. (2016). Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice. Aging cell.

[12] Childs, B. G., Baker, D. J., Wijshake, T., Conover, C. A., Campisi, J., & van Deursen, J. M. (2016). Senescent intimal foam cells are deleterious at all stages of atherosclerosis. Science, 354(6311), 472-477.

[13] Palmer, A. K., Tchkonia, T., LeBrasseur, N. K., Chini, E. N., Xu, M., & Kirkland, J. L. (2015). Cellular senescence in type 2 diabetes: a therapeutic opportunity. Diabetes, 64(7), 2289-2298.

[14] Velarde, M. C., & Demaria, M. (2016). Targeting Senescent Cells: Possible Implications for Delaying Skin Aging: A Mini-Review. Gerontology.

[15] Xu, M., Bradley, E. W., Weivoda, M. M., Hwang, S. M., Pirtskhalava, T., Decklever, T., … & Lowe, V. (2016). Transplanted Senescent Cells Induce an Osteoarthritis-Like Condition in Mice. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, glw154.

[16] Lluc Mosteiro, Cristina Pantoja, Noelia Alcazar et al. (2016) Tissue damage and senescence provide critical signals for cellular reprogramming in vivo. Science, 354(6315).

[17] Demaria, M., Ohtani, N., Youssef, S. A., Rodier, F., Toussaint, W., Mitchell, J. R., … & Hoeijmakers, J. H. (2014). An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Developmental cell, 31(6), 722-733.

[18] Tominaga, K. (2015). The emerging role of senescent cells in tissue homeostasis and pathophysiology. Pathobiology of Aging & Age-Related Diseases, 5.

[19] Matjusaitis, M., Chin, G., Sarnoski, E. A., & Stolzing, A. (2016). Biomarkers to identify and isolate senescent cells. Ageing research reviews, 29, 1-12.

About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 600 articles on the topic, interviewed over 100 of the leading researchers in the field, hosted livestream events focused on aging, as well as attending various medical industry conferences. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Swiss Monthly, Keep me Prime, and New Economy Magazine. Steve is one of three recipients of the 2020 H+ Innovator Award and shares this honour with Mirko Ranieri – Google AR and Dinorah Delfin – Immortalists Magazine. The H+ Innovator Award looks into our community and acknowledges ideas and projects that encourage social change, achieve scientific accomplishments, technological advances, philosophical and intellectual visions, author unique narratives, build fascinating artistic ventures, and develop products that bridge gaps and help us to achieve transhumanist goals. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project.
  1. July 22, 2018

    great article.

  2. October 8, 2018

    Is there a chance your company will be producing a supplement

    • Steve Hill
      October 8, 2018

      Hi Jonathan, we are a non-profit charitable foundation and cannot produce such things. Our role is to report the research news, educate, advocate, fundraise for research, and conduct outreach for the field of rejuvenation biotech. We do report on senolytic research and sometimes that includes coverage of compounds found in supplements but we are not a manufacturing company and will not produce supplements or drugs.

  3. HealthequalsLifeTime
    April 3, 2021

    Good article.

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