Calorie Restriction Reduces the Number of Senescent T Cells in Older Mice

A sizable enough fraction of T cells of the adaptive immune system become senescent in old age to cause major issues. Senescent cells cease replication and secrete a mix of signals that cause harm in numerous different ways: rousing chronic inflammation; disrupting tissue maintenance and structure; encouraging other cells to become senescent. The cell dynamics of the immune system are quite different from those of tissues. Immune cells are provoked into replication by signals of damage or infection, and enough of that sort of stress over time will have large effects on the number of senescent immune cells.

Somatic cells, such as T cells, can only replicate a set number of times before they reach the Hayflick limit and become senescent or self-destruct. The supply of new T cells is reduced with age, as the thymus, where thymocytes mature into T cells, atrophies. Reduced supply and increased replication stress due to damage, infection, and other disarray in the immune system leads to a growing number of senescent T cells. This is the case in aging, and also the case in conditions such as HIV infection, in which the thymus is damaged and the immune system put under great stress.

In today's open access paper, researchers show that the practice of calorie restriction slows the accumulation of senescent T cells with age. Additionally, clearing these senescent T cells via a suitably targeted therapy also produces similar benefits. A range of other evidence has pointed to senescent and senescent-like subpopulations of T cells that arise with age, and researchers have shown that these cells produce all sorts of problems in later life. This is all the more reason to place a greater emphasis on, firstly, the production of senolytic therapies to destroy these errant cells, and, secondly, on ways to restore a more youthful production of T cells in the bone marrow and thymus.

The effect of caloric restriction on the increase in senescence-associated T cells and metabolic disorders in aged mice

Aging is associated with functional decline in the immune system and increases the risk of chronic diseases owing to smoldering inflammation. In the present study, we demonstrated an age-related increase in the accumulation of PD-1+ memory-phenotype T cells that are considered "senescence-associated T cells" in both the visceral adipose tissue and spleen. As caloric restriction is an established intervention scientifically proven to exert anti-aging effects and greatly affects physiological and pathophysiological alterations with advanced age, we evaluated the effect of caloric restriction on the increase in this T-cell subpopulation and glucose tolerance in aged mice.

Long-term caloric restriction significantly decreased the number of PD-1+ memory-phenotype CD4+ and CD8+ T cells in the spleen and visceral adipose tissue, decreased pro-inflammatory M1-type macrophage accumulation in visceral adipose tissue, and improved insulin resistance in aged mice. Furthermore, the immunological depletion of PD-1+ T cells also reduced adipose inflammation and improved insulin resistance in aged mice.

These results indicate that senescence-related T-cell subpopulations are involved in the development of chronic inflammation and insulin resistance in the context of chronological aging and obesity. Thus, long-term caloric restriction and specific deletion of senescence-related T cells are promising interventions to regulate age-related chronic diseases.


Old folk are usually frail and eat very little. You would think that would be beneficial..

Posted by: person12345 at June 28th, 2021 3:58 PM

I was thinking about that. Probably reduced calorie absorption/intake as at least a couple of years to the lifespan

Posted by: Cuberat at June 28th, 2021 7:30 PM

Yes, seniors may eat less calories but are they healthy calories? Also I don't think reckless malnutrition is life extending.

Posted by: Allen at June 28th, 2021 10:19 PM

Hmm.. what I've seen long term CR in humans leads to frailty, infertility, psychological disorders, etc.. No doubt it will reduce the number of all kind of cells, but not in a selective manner.

Posted by: Jones at June 30th, 2021 3:54 AM
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