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A Problem Population of Monocytes are Found to be Senescent Cells


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Posted 10 October 2018 - 10:23 AM


The Life Extension Advocacy Foundation volunteers here note an open access paper from earlier this year. The authors characterize a small, problematic population of the immune cells known as monocytes as being senescent cells, having the same character of inflammatory signaling and disruptive behavior as other types of senescent cell. This finding is one of many discoveries emerging from the great expansion of funding and interest in cellular senescence that has taken place in recent years. The accumulation of senescent cells is an important cause of aging and age-related disease, but broad recognition of this point has required a great deal of time and hard work. Now that research in this field has picked up, the consensus on a range of cell types and behaviors, those observed in age-related disease and known to be harmful, is likely to be revised in the direction of the involvement of cellular senescence.

Monocytes are immune cells that can differentiate into macrophages and are involved in the processes of both innate and adaptive immunity. There are three known types of monocytes: classical, intermediate, and nonclassical. The nonclassical ones are the most pro-inflammatory even though they express high levels of miR-146a, a microRNA that is known to limit inflammatory responses. This apparent contradiction is what led the authors of this study to discover if there is more to miR-146a than meets the eye.

Cellular senescence is a phenomenon by which normal cells stop dividing and begin secreting a highly inflammatory cocktail of chemicals known as the senescence associated secretory phenotype (SASP). In modest amounts, senescent cells have beneficial roles; however, they tend to accumulate as we age, which results in a constant, low-grade inflammation as well as a higher susceptibility to a range of age-related diseases, cancer included, in the elderly. Given that the elevated pro-inflammatory activity of nonclassical monocytes is rather reminiscent of the SASP and that they display such high levels of miR-146a, the scientists reasoned that nonclassical monocytes may well undergo senescence.

Scientists found that elderly patients display an accumulation of these cells compared to younger people. They collected samples from 30 healthy volunteers between the ages of 22 and 35 years and 30 healthy elderly people aged 55 and older. While there was no significant difference in the total percentage of any of the three monocyte types between the two groups, the researchers found out that the elderly had a higher monocyte count per volume of blood, especially nonclassical monocytes. Accordingly, the level of inflammatory cytokines in the blood of the elderly was significantly higher. This led the scientists to conclude that senescent monocytes do indeed accumulate in the blood of the elderly and may well contribute to inflammaging, which is the chronic, low-grade inflammation that is typical among older people.

The researchers suggest that nonclassical monocytes might be a viable target for treating age-related and chronic inflammatory conditions, even non-age-related ones. It may be possible to reduce the SASP secreted by nonclassical monocytes or reduce the number of circulating nonclassical monocytes.

Link: https://www.leafscie...rgo-senescence/


View the full article at FightAging




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