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Cellular Senescence: The Good, the Bad, and the Ugly

From the moment you are born, your body must constantly choose between promoting cell division and halting cell division. The delicate balance achieved between the promotion and termination of cell division regulates how your body grows, repairs damaged tissue, and ages. However, as we age, our tissues overwhelmingly accumulate cells that have irreversibly ceased to divide, known as “senescent cells.” Read on to learn more about cellular senescence and its impact on aging and how to better manage your  body’s senescent cell burden. 

Cellular senescence is a stable form of cell cycle arrest (when your cells stop working properly) triggered by various factors, including DNA damage, mitochondrial dysfunction, and telomere shortening. (1) Cellular senescence is neither good nor bad; depending on where and when it occurs in the body, it can exert beneficial or detrimental effects. 

Scientists have identified two main types of cellular senescence in the body:

  • Acute senescence and chronic senescence. Acute cellular senescence plays vital positive roles inside the body, inhibiting the growth of malignant cells, regulating development, and supporting wound healing. (2
  • Chronic senescence promotes biological aging or the gradual deterioration of physiological function that occurs as our cells and tissues accumulate damage over time. (3

The trouble with chronic senescent cells is that they secrete an array of inflammatory compounds, referred to as the “senescence-associated secretory phenotype” (SASP), that damage the cells around them. Playfully referred to as “zombie cells,” senescent cells are instigators of the coined term “inflammaging,” or ongoing low-grade inflammation that develops with age and contributes to age-related dysfunction. 

How does cellular senescence affect the  body? 

  • Impaired frontline immune defenses against foreign invaders and “immunological memory,” or the immune system’s ability  to respond rapidly and efficiently to bugs it has previously encountered (4)
  • Aging of the endothelial lining of blood vessels, which compromises oxygen and nutrient delivery to tissues and organs (5)
  • Accumulation of plaque in blood vessels, increasing cardiovascular  (6
  • Accumulation of misfolded proteins in the central nervous system, contributing to aging and declines in brain function (7)
  • Accumulation of fat in the liver, causing liver and metabolic impairments (8)

The Critical Connection Between Senescence and Telomeres

Telomeres are the tiny microscopic “caps” at the end of chromosomes that protect them from coming apart over a lifetime of cell division. Unfortunately, telomeres shorten with age compromising chromosome integrity and our health. Telomere shortening or attrition is another key hallmark of aging in longevity science and believe it or not, is closely connected to cellular senescence. (9)

In fact, telomere shortening can trigger cellular senescence through its role in creating DNA damage, which is read as a ‘danger signal’ by the body. When the body recognizes this danger signal, cellular senescence is initiated in an attempt to inhibit replication of damaged cells. The obvious downside is that the senescent cells can ultimately have a net negative effect on the entire body and driving aging. (11) Regulating telomere shortening may be crucial for slowing cellular senescence and promoting healthy aging. 

Senolytics to the Rescue!

While cellular senescence is a natural part of aging, burgeoning levels of senescent cells are clearly problematic for our health and aging process.

Senolytics, or compounds that selectively induce the death of senescent cells, can help our bodies manage senescent cell populations, supporting healthier cells and tissues.

Senolytics show several exciting benefits in longevity research. For example, senolytics have been found to:

  • Support healthy kidney function with age (12)
  • Safeguard intervertebral discs, which tend to break down with age due to senescence (13)
  • Support healthy immune system function (14
  • Support healthy blood sugar regulation (15

Several natural compounds demonstrate senolytic properties. Quercetin, a flavonoid found in onions, capers, grapes, and berries, has been shown to regulate the number of senescent cells in the body, supporting a balanced inflammatory response. (16, 17) Curcumin and Panax notoginseng also demonstrate senolytic effects, creating a tissue microenvironment that is more conducive to healthy aging. (18, 19, 20

Exercise: A Lifestyle-Based Senolytic 

We all know that exercise supports healthy aging.  However, it wasn’t until recently that scientist’s uncovered the physiological mechanisms by which regular physical activity stems the tide of aging. One such body of research suggests that exercise may support healthy aging by inhibiting cellular senescence! It shows that  exercise reduces markers of senescent cells in healthy humans; for example, the habitual level of physical activity in healthy participants is negatively associated with levels of p16INK4a, a protein released during cellular senescence.  (21) Exercise may inhibit senescence by regulating autophagy, the body’s cellular “housekeeping” system that removes damaged, dysfunctional cell components to make space for new, healthy cells. 

So what can we do? In 2018, the Department of Health and Human Services (HHS) published exercise guidelines for Americans that urge us to aim for 150 minutes of moderate-intensity physical activity or 75 minutes of vigorous-intensity aerobic activity per week. Adults are also encouraged to do two or more bouts of strength training per week. (22) Do we know whether or not these guidelines are sufficient enough to attenuate cellular senescence? We are needing more scientific data to be sure but it is certainly a good place to start!  

Cellular senescence is a natural part of our life cycle, but excessive cellular senescence is detrimental to the biological aging process. Through strategic supplementation and a healthy lifestyle that involves regular physical activity, we are doing our part to help our bodies age with health and vitality. 

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