Senescent Cells: Friends or Foes? Dr. Domenico Pratico'. MD, FCPP

The word "senescence" comes from the Latin “senex” (meaning "old" or "elderly"), and the verb “senescere” (meaning "to grow old"), and typically refers to the process of growing old or the state of being old.

At time the word “senescence” is used interchangeably with “aging”, however although they both relate to the process of growing older, they are different.

Aging is the progressive deterioration of an organism over time, encompassing physical and mental decline.

Senescence refers to a specific cellular process where cells permanently stop dividing.

Growing old is part of the human life cycle.

Until the 1960s there was a common belief that when in a Petri dish cells could replicate continuously. However, two scientists (Leonard Hayflick, and Paul Moorhead), showed that there was a limit on the number of replications, and that once it was reached, cells would enter a phase known as “senescence”.

However, for a while this aspect was considered almost an artifact because the cells were in a tube and that this was not possible inside a living organism. Surprisingly, in the last two decades mounting evidence shows that indeed “senescence” also happens inside a living body.

A young and an old cell in the same environment.

Senescent cells are unique in that they stop multiplying but do not die. By contrast, they stay where they are and continue to release chemicals that can initiate an inflammatory response damaging other cells nearby that are healthy.

Various factors can trigger senescence, among them:

• Shortening of protective caps on the chromosomes (aka telomers)

• Damage to the DNA

• Radiation

• Oxidative stress

Various factors can trigger cellular "senescence".

Today we know that “senescence” happens in any cell type and any organ in our body and can have both physiological and pathological roles.

Physiologically, it is essential for embryogenesis and development and is a safeguard against tumorigenesis by preventing the proliferation of damaged or defective cells.

Importantly, when it takes place, our body uses specific mechanisms to remove those cells. With age our body becomes less efficient at doing this important task and these cells accumulate. When this happens, senescent cells start to secrete inflammatory molecules which promote chronic inflammation and subsequent tissue damage, which are implicated in multiple aging-associated disorders such as Alzheimer's disease.

Cellular senescence can be prevented and controlled through lifestyle interventions as well as pharmacological approaches. These strategies aim to clear or inhibit senescent cells, thereby promoting tissue health, reducing inflammation, and improving overall well-being.

Lifestyle Interventions

Exercise: Regular physical activity, including running, walking, or jogging

Diet: A diet rich in antioxidants, vitamin D, protein, and phytochemicals (like resveratrol and quercetin)

Stress management

Good night sleep

With age, there is often a progressive accumulation of senescent cells in various organs including the brain. If not promptly removed they can cause harm.

Pharmacological and Therapeutic Approaches

Senolytics:

These drugs selectively induce apoptosis (programmed cell death) in senescent cells, removing them from the body. Examples include the combination of dasatinib and quercetin. Researchers are developing drugs called senolytics that selectively eliminate senescent cells, which has shown promise in preclinical models for alleviating age-related conditions.

Senomorphs:

These agents aim to suppress the harmful factors released by accumulating senescent cells, known as the senescence-associated secretory phenotype.

Rapamycin: this drug has been shown to reduce senescence and improve immune function, extending the health span in animal models.

In general, these strategies work by reducing senescence biomarkers and inflammatory markers while increasing beneficial proteins such as sirtuins. They also can restore tissue homeostasis by decreasing the burden of senescent cells and their harmful secretions, and promoting the normal functioning of tissues and organs.

In summary, senescent cells can be found in an adult living organism where if they not promptly removed can trigger pro-inflammatory reactions with subsequent tissue or organ damage.

While more studies are needed to better characterize this process, there are few steps that can be taken by everybody to reduce the negative impact that the piling up of senescent cells can have on an organism.    

Please remember, it is never too early and never too late to adopt these measures against the accumulation of senescence cells and their negative effects!   

If you are interested in reading more of my blogs:

Check out the recent blog: A Good Diet for the Brain  ~ Dr. Domenico Pratico', MD, FCPP

Dr. Domenico Pratico' , MD, FCPP

Domenico Praticò, MD, holds the Scott Richards North Star Charitable Foundation Chair for Alzheimer’s Research and serves as a Professor and Founding Director of the Alzheimer’s Center at Temple, as well as a Professor of Neural Sciences at Lewis Katz School of Medicine at Temple University.

For more information on the research conducted by Dr. Domenico Pratico, please visit this link.

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