Thoughts on Calorie Restriction and Senescent Cells

A commentary on recent research showing calorie restriction to reduce the number of senescent cells in some tissues: "The relatively short period of caloric restriction resulted in a 3.3 to 6.5% decrease in senescent cell abundance as a function of total cell number. ... As with many interesting studies, this study raises many more questions than it answers. ... Does short term caloric restriction reduce the proportion of senescent cells in other tissues, such as fat? Obesity, aging, and other conditions are associated with extensive accumulation of senescent cells in fat tissue of rodents as well as humans ... Does short term caloric restriction also reduce abundance of senescent cells and inflammation in humans? It may not, since, as the authors point out, proliferation-competent skin fibroblasts did not increase after 9 to 12 years of caloric restriction in rhesus monkeys. On the other hand, it might, since white blood cell DNA fragmentation [declines] in overweight but non-obese adult human subjects subjected to 25% caloric restriction for 6 months ... What is the cell dynamic mechanism that causes decreased senescence during short term caloric restriction? Altered rates of senescent cell formation or removal could be responsible for the effect of short term caloric restriction on abundance of senescent cells. ... Senescent cells can be removed through activation of the immune system, with the immune system being activated by factors released by senescent cells. Short term caloric restriction could enhance immune system responsiveness to senescent cells, a possibility that remains to be tested."



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