What is Cellular Senescence?

The Hayflick limit suggests that a normal human cell can replicate and divide roughly fifty times before it cannot divide anymore (this is known as ‘replicative senescence’). Certain stressors mean that a cell can become senescent before it reaches the Hayflick limit.

Cellular senescence is a phenomenon in which cells cease to divide but remain metabolically active. This means they are still ‘alive’ and growing, creating energy, and generating and eliminating waste. A senescent cell is notably enlarged, which is due to their growth in the absence of division. 

Common cellular stressors—such as oxidative stress, DNA damage, and mitochondrial dysfunction—can also trigger cellular senescence in cells before they lose their ability to proliferate. Though no longer able to divide, because senescent cells remain metabolically active, they secrete numerous pro-inflammatory and proteolytic (enzymes that break down protein) factors as part of the senescence-associated secretory phenotype (‘SASP’), a profile marked by the secretion of proinflammatory cytokines, among other damaging mechanisms. These SASP factors are thought to stimulate the removal of senescent cells by the immune system.

Senescent cells have been shown to accumulate with age; a phenomenon that impedes innate and adaptive immune responses.

As the burden of senescent cells increases, the SASP can alter the local microenvironment, altering tissue structure and function. Whether the increasing burden of senescent cells impairs immune function, or the failure of the aging immune system to remove senescent cells enables their accumulation, remains to be understood.

What is immunosenescence?

Immunosenescence broadly describes age-related decline in the immune system. Cells of the immune system, such as B, T, and NK (Natural Killer) cells, are crucial to a robust immune system. B cells are responsible for producing antibodies, while T cells provide cell immunity. NK cells are part of the innate immune system which is the first line of your body's defense.

These cells have been shown to become senescent in healthy elderly individuals, which is believed to contribute to age-related immune decline. For instance, senescent B cells have an impaired ability to proliferate, differentiate, and generate an optimal antibody response.  Senescent immune cells are also believed to contribute to age-related inflammation – or inflammaging – observed in older adults, owing to the unique SASP that they acquire.

Senolytics and the immune system

Techniques to remove senescent cells from the body, using a class of compounds called senolytics, like those found in our advanced immune product Format, are emerging as a viable approach to alleviate conditions associated with increased senescent cell burden and to support healthy cellular aging. Senolytics selectively target senescent cells’ pro-survival mechanisms, without compromising the viability of neighboring healthy cells. In this sense they are like special ops—sent in to take care of very specific issues without negatively impacting their surroundings. 

By targeting senescent cells, senolytics actually support a healthy aging process on a cellular level within the body, thus promoting the proper function of tissues and organs within the body and supporting the immune system.


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