What is a senescent cell?
A senescent cell is one whose life cycle has come to a permanent end. In the normal scheme of things, such cells are eliminated from the body by the immune system. But in some cases, this fails to happen and they accumulate in tissues, with potentially serious consequences for health.
The causes of senescence
The process of replicative senescence is naturally initiated in cells as they age. It is triggered by the shortening of telomeres, the DNA sequences found at the tips of chromosomes, which become shorter with each successive DNA replication. After a certain point, this replication of DNA ceases, and the cell stops dividing before dying a natural death. Scientists have recently shown that stress leads to an acceleration in cellular ageing by intensifying this telomere-shortening. (1)
There are also external triggers of senescence such as oxidative stress. In a similar way to radiation or UV, oxidative stress damages DNA. Sometimes the cell is able to repair the DNA and ‘restart the machine’, but in other cases, the cell enters senescence in order to be destroyed.
Finally, senescence can be induced by hyperactivation of genes which usually encourage proliferation of cells and therefore cancer. When faced with such hyperactivation, cells respond by entering senescence.
What happens to the senescent cell?
The senescent cell becomes enlarged and flatter, structural changes occur in its chromatin (the ‘framework’ in which DNA is contained), it becomes unreceptive to cell growth and suicide factors … In short, it ensures a permanent end to its activity and multiplication. In addition, the senescent cell secretes pro-inflammatory molecules which summon the immune system responsible for eliminating and destroying dead cells. In this way, senescence and its immune-activating entourage often contribute to inhibiting the development of tumours.
However, in what is a particularly complex molecular process, it can happen that senescence promotes tumour proliferation in the cell’s surrounding environment. The inflammatory molecules secreted by senescent cells may encourage neighbouring cells to convert into pre-cancerous cells and then foster their proliferation. (2)
Note
Research has recently identified the proliferative capacity of senescent cells during embryo development. (3)
The pathological consequences of senescence
Senescence is one of the body’s natural mechanisms of ageing and its characteristic markers such as wrinkles or skin slackening. But it is also a cause of certain diseases, as we’ve seen with cancer. The immune system’s failure to destroy senescent cells leads to excessive inflammation and the development of metabolic inflammatory conditions such as obesity and type 2 diabetes.
Senescence is also implicated in arthritis, osteoporosis and atherosclerosis (stiffening of the arteries), as well as in neurodegenerative diseases such as Parkinson’s or Alzheimer’s. (4)
Senolytics, a hopeful option for life expectancy
To maintain good health for as long as possible, the most important recommendation is still to adopt a sensible lifestyle. But particularly promising molecules called senolytics might also play a positive role in the future. (5) An emerging area of anti-ageing research for some years now, these compounds could work against senescence and thus slow down the ageing process.
Offering potential for preventing the above-mentioned diseases, these senolytics include molecules already present in nature, the most promising of which have been identified as:
- fisetin, a flavonoid naturally present in acacia, strawberries and mangos, for example;
- and quercetin, another flavonoid found in capers, chilis, red onions and elderberries …
They are also available in supplement form (such as Fisetin and Senolytic Complex): an invaluable aid to slowing down the ageing process!
References
- Herranz, N. & Gil, J. Mechanisms and functions of cellular senescence. J. Clin. Invest. 128, 1238–1246 (2018).
- Campisi, J. & d’Adda di Fagagna, F. Cellular senescence: when bad things happen to good cells. Nat. Rev. Mol. Cell Biol. 8, 729–740 (2007).
- Storer, M. et al. Senescence Is a Developmental Mechanism that Contributes to Embryonic Growth and Patterning. Cell 155, 1119–1130 (2013).
- Muñoz-Espín, D. & Serrano, M. Cellular senescence: from physiology to pathology. Nat. Rev. Mol. Cell Biol. 15, 482–496 (2014).
- Kirkland, J.L., Tchkonia, T., Zhu, Y., Niedernhofer, L.J. and Robbins, P.D. (2017), The Clinical Potential of Senolytic Drugs. J Am Geriatr Soc, 65: 2297-2301.
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