The effects of graded caloric restriction: XII. Comparison of mouse to human impact on cellular senescence in the colon

Abstract

SummaryCalorie restriction (CR) is an effective strategy to delay the onset and progression of aging phenotypes in a variety of organisms. Several molecular players are involved in the anti‐aging effects of CR, but mechanisms of regulation are poorly understood. Cellular senescence—a cellular state of irreversible growth arrest—is considered a basic mechanism of aging. Senescent cells accumulate with age and promote a number of age‐related pathologies. Whether environmental conditions such as diet affect the accumulation of cellular senescence with age is still unclear. Here, we show that a number of classical transcriptomic markers of senescent cells are reduced in adult but relatively young mice under CR. Moreover, we demonstrate that such senescence markers are not induced in the colon of middle‐age human volunteers under CR in comparison with age‐matched volunteers consuming normal Western diets. Our data support the idea that the improvement in health span observed in different organisms under CR might be partly due to a reduction in the number of senescent cells.

Cellular Senescence as a Therapeutic Target for Age-Related Diseases: A Review

“…Within the first group, studies in mice have shown that a 3-month, 26% calorically restricted diet started at adulthood can reduce the number of senescent cells in rapidly proliferating (intestinal) and slowly proliferating (hepatic) tissues [104]. A study of the human colonic mucosa showed that adults who had been voluntarily exposed to a 30% caloric restriction (with appropriate nutrition) for over 10 years had significantly reduced expression of p16 INK4a and reduced local concentrations of IL-6 [105]. A recent study in mice demonstrated that calorie restriction, even if started at adulthood, prevents fat deposition and the concomitant increase in telomere-associated DNA damage foci (TAF) in hepatocytes [106].…”

Caloric restriction and cellular senescence

“…Different studies have shown that CR reduce senescence markers in different mouse organs and human colon mucosa 9,[63][64][65][66] . One of the main inducers of senescence is cellular damage.…”

The aging proteostasis decline: From nematode to human

“…[ 98 , 99 ]), and has also been demonstrated to substantially improve proteostasis in aged nematodes [ 7 , 109 , 110 ]. In humans, caloric restriction was shown to improve proteostasis [ 111 ] and reduce markers of senescence [ 112 ]. Interestingly, specific dietary supplements have been shown to improve the proteostasis capacity in aged nematodes, including oleic acid [ 113 ] and arachidonic acid [ 110 ], which was found to modulate HSF1 function [ 114 ].…”