Inflammation and Senolytics

With people over 60 experiencing the fastest growth rate, the world’s population is ageing quickly. Ageing is associated with cellular senescence, which is linked to chronic, low-grade, sterile inflammation.

What Is Cellular Senescence?

Cellular senescence is a process in which cells stop dividing and exhibit distinct phenotypic changes. Hayflick and Moorhead coined the term “cellular senescence” for the first time in 1961. They described the phenomenon as an irreversible growth arrest of a human diploid cell(containing two complete sets of chromosomes, one from each parent) which remained metabolically active after a prolonged time in culture.

Cellular senescence can be triggered in normal cells in response to a wide range of stress-inducing factors. These factors include both external and internal damaging events like abnormal cellular growth, oxidative stress, DNA damage, reactive metabolites, and toxins.

During normal development, cellular senescence restricts the uncontrolled growth of aged and damaged cells. However, it is also associated with ageing and induces age-related pathologies.

Normally, our body effectively removes senescent cells, making place for new, healthy cells. However, as we get older, our body produces more senescent cells; at the same time, mechanisms for getting rid of the extra senescent cells become less efficient. Consequently, our tissues experience a net buildup of senescent cells. This contributes to many age-associated conditions, including cancer, tissue degeneration and inflammation.

What Is Cellular Inflammation?

Cellular inflammation is a double-edged sword; it functions as an important immune response against pathogenic disturbances and maintains biological stability. However, inflammation can also occur due to ageing-associated accumulation of senescent cells.

Senescent cells secrete proinflammatory substances, which create a micro environment of “chronic low-grade inflammation”, also known as “inflammaging”. This phenomenon persists both in tissues and organs and is a hallmark for most ageing-related diseases.

Unfortunately, this inflammation does not stop with a single cell. Senescent cells act similarly to neighbouring cells as a rotten apple in a basket does to neighbouring apples. The released proinflammatory substances attack healthy cells and transform them into senescent cells. Due to this, senescent cells are also called zombie cells.

The situation worsens as senescent cells secrete substances that allow immune cells into senescence, thereby reducing the number of immune cells available to fight pathogens and other damaging stimuli.

As cellular senescence could contribute to both age-related and chronic disease-related inflammation, therefore specifically targeting senescent cells can disrupt the link between ageing, immune dysfunction and diseases, potentially delaying age-related conditions.

Senolytics as an Anti-Inflammation Agent

Eliminating senescent cells and preventing the accumulation of senescent cells is an effective way of slowing ageing and age-related diseases.

The elimination of senescent cells is done perfectly by senolytics, a class of small molecules that can selectively induce death in senescent cells and improve health in humans. Senolytics promote self-destruction in senescent cells, thus reducing chronic inflammation and enhancing tissue regeneration. Senolytics are considered to be a viable treatment for some aspects of ageing and may even promote healthy longevity.

Bottom Line

Ageing and many age-associated chronic diseases that account for the majority of deaths, morbidity, and medical costs in contemporary society could be linked to chronic inflammation, cellular senescence, or other fundamental ageing mechanisms.
Senolytic compounds such as Dasatinib, Fisetin and Quercetin are the most popular drugs for killing senescent cells. This is backed by several studies which demonstrate that the senolytic treatment reduces cellular senescence and inflammation.