Turning Back the Clock on Ageing- Senescent Cells and Old Age

Brent Bauer, M.D., Mayo Clinic

March 31, 2021

There is no question that people are living longer. Between 2000 and 2015, the average global life span around the world increased by five years; although during that same time, the average “health span” only increased by 4.6 years. This means people are living longer but they are struggling with chronic health conditions associated with age, like cancer, dementia, arthritis, and others.1  

Much research is underway on ways to increase health span – delaying the onset of disease and disability to live a healthier, higher quality of life. One area of interest is the role of senescent cells in ageing and whether their removal can pause or slow the clock on chronic conditions that come with age. 

What Are Senescent Cells? 

One of the most significant biological processes of ageing is cellular senescence. Senescence literally means “the process of growing old.” 

To maintain health, most cells in the body continually divide to replace old and damaged tissue. Eventually cells age, stop dividing, and die. It is estimated that in adult humans 100 billion cells die each day and are replaced by new cells. The mass of cells you lose each year through normal cell death is close to your entire body weight.2 

When ageing and damaged cells die, your immune system clears them from your body. Senescent cells, on the other hand, are malfunctioning cells that have stopped dividing but do not die and remain in the body. Damage to cells caused by disease or environmental factors, like cigarette smoke, can cause cells to become senescent.3,4 

Although senescent cells are relatively few, they can accumulate with age and build up in tissues throughout the body. They contribute to cancer and multiple other conditions associated with ageing, including frailty, dementias, osteoporosis, diabetes, and heart, kidney, liver, and lung diseases.3,4   

How Do Senescent Cells Cause Disease and Ageing? 

Although the mechanisms of how senescent cells cause disease and dysfunction are still being defined, research is indicating that inflammation plays a large role. 

Senescent cells secrete a harmful mix of cytokines, chemokines, and other proteins. This secretion, called senescence-associated secretory phenotype (SASP), causes inflammation that impairs the function of the healthy cells around them and damages the tissues in which the senescent cells reside. This contributes to organ dysfunction and the development of age-related disorders throughout the body.3,4 

Part of unlocking the puzzle of senescence cells is determining why they don’t die – despite being damaged. Researchers think part of the answer lies in a family of proteins that regulate a type of cell suicide known as apoptosis. Apoptosis is the natural process of programmed cell death. Apoptosis rids the body of cells that are no longer needed or that are damaged beyond repair. If apoptosis is somehow prevented, then it can lead to uncontrolled cell division and cause cancerous growths.2  

Research has shown that clearing senescent cells from the body does halt certain aspects of ageing and disease.3,4 As far back as 2011, research lead by Mayo Clinic showed that systematically eliminating senescence cells in mice delayed the onset of cataracts and reduced age-related muscle loss and function.5 

In recent experiments, Mayo researchers fed mice a compound they previously proved could selectively kill senescent cells: dasatinib, a drug used with chemotherapy, and quercetin, a flavonoid found in onions and apples. The result? Within weeks after receiving treatment, the mice ran further, did better on physical testing, and were 36-percent less likely to die than mice injected with senescent cells who didn’t receive the drug.6,7 

Possible Treatment for Disease and Disorders That Come with Age 

Researchers continue to identify compounds that target senescent cells. Called “senolytics,” this new class of drugs selectively kills and clears senescent cells from the body. By targeting senescent cells in mice, research is showing that we can delay, prevent, or treat multiple diseases and increase health and independence during the later years of life.4

Scientists are working on ways to use senolytics in hopes of treating diseases and alleviating the ravages of old age.4,8 In 2019, researchers demonstrated that senolytics can safely target senescent cells in humans. The study included 14 patients with idiopathic pulmonary fibrosis – a disease that causes scarring in the lungs, making it difficult to breath.9

Although the primary goal was to evaluate the treatment’s safety, researchers saw signs that the drugs might be working. After taking three oral doses a week for three weeks, patients could walk further in six minutes than they could at the start of the trial, and they performed better on other tests of their physical abilities, such as standing up from a chair.9 

Natural Therapy for Cellular Senescence: Exercise  

Although preliminary research is encouraging on the effectiveness of using senolytic drugs to ward off disorders associated with ageing, it does not mean these drugs should be prescribed by physicians to their patients – especially because there is no need to wait for a therapy to eliminate senescent cells from the body. Exercise can help do the trick.  

Exercise has a profound effect on cells and their capacity to repair different aspects of damage that is linked to ageing and age-related diseases. It is widely accepted that exercise gets rid of old damaged cells and improves the ability of cells to heal the body, repair DNA and manage oxidative stress.  

One recent study illustrated that in the context of obesity, exercise can prevent senescent cell accumulation and, to some extent, clear senescent cells from the body.10 

It sounds repetitive, but the recommended guidelines to maintain overall good health also apply to ageing. Moderate-to-vigourous exercise 30 minutes daily on most days of the week will benefit the body and its ability to maintain health and prevent disease. In contrast, lack of exercise and unhealthy eating are linked to age-related cell damage and chronic disease. 

Simply moving your body with physical activity and exercise can turn on your body’s natural healing capacity to help slow the clock on ageing – and that’s in your control.   

  1. Song S, Lam E, Tchkonia T, et al. Senescent cells: Emerging targets for human ageing and age-related diseases. Trends Biochem Sci 2020;45(7):578-592. 
  2. Gilbert S. Developmental Biology. 6th edition. The cell death pathways. Sunderland (MA): Sinauer Associates; 2000. 
  3. van Deursen J. The role of senescent cells in ageing. Nature.2014;509(7501):439-446. 
  4. Kirkland J, Tchkonia T. Cellular senescence: A translational perspective. EBioMedicine 2017;21:21-28. doi:10.1016/j.ebiom.2017.04.013
  5. Baker D, Wijshake T, Tchkonia T, LeBrasseur K. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 2011; 479(7372): 232-236. 
  6. Xu M, Pirtskhalava T, Farr J, et al. Senolytics improve physical function and increase lifespan in old age. Nat Med 2018;24(8):1246-1256. 
  7. Zhu Y, Tchkonia T, Pirtskhalava T, et al. The Achilles’ heel of senescent cells: From transcriptome to senolytic drugs. Ageing Cell 2015;14(4):644-58.  
  8. Kirkland J, Tchkonia T. Senolytic drugs: From discovery to translation. J Intern Med 2020;288(5):518-536.
  9. Justice J, Nambiar A, Tchkonia T, et al. Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study. EBioMedicine 2019;40:554-563. 
  10. Schafer M, White T, Evans G, et al. Exercise prevents diet-induced cellular senescence in adipose tissue. Diabetes 2016;65(6):1606-1615.

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