An interesting question with regard to the growth in the age-related burden of senescent cells is the degree to which it is altered by lifestyle choice. Or, to put it another way, we know the degree to which better lifestyle choices affect pace of aging and life expectancy: how much of that effect is due to a reduced burden of senescent cells? Can the existing burden be reduced by better lifestyle choices, and by how much? Here, researchers review the evidence for dietary lifestyle choices to influence cellular senescence and find it lacking, as the existing body of clinical trial data is not large enough and consistent enough to support definitive statements. As the researchers note, the data is supportive of the hypothesis that dietary choice has more of an impact on the behavior rather than number of senescent cells. The burden remains.
Cellular senescence is a fundamental mechanism of ageing, characterised by stable cell cycle arrest and the acquisition of a pro-inflammatory secretory phenotype (SASP). Nutritional interventions are widely proposed to modulate ageing biology, but their effects on cellular senescence in humans remain unclear. We systematically synthesised evidence from interventional human studies assessing the impact of nutritional strategies on biomarkers of cellular senescence.
Twenty-nine articles (27 trials; 3,811 participants) were included. Across studies, nutritional interventions modulated multiple senescence biomarkers to varying extents, with calorie restriction producing the most recurrent reductions in circulating inflammatory and secretory factors commonly included in SASP panels as well as senescence-associated transcriptomic signatures. Classical markers of cell cycle arrest (e.g., CDKN2A/p16, CDKN1A/p21) and telomere length were largely unchanged or highly variable. Calorie restriction mimetics, particularly metformin and rapamycin, showed context-dependent effects, most evident under conditions of metabolic or physiological stress. Among dietary supplements, n-3 polyunsaturated fatty acids may modulate selected inflammatory/SASP-related circulating markers, although the evidence for dietary supplements remains limited and heterogeneous.
In humans, available evidence suggests that nutritional interventions may preferentially affect senescence-associated inflammatory and secretory biomarker profiles, particularly SASP-related mediators, rather than markers more directly related to senescent cell abundance. However, because SASP factors and circulating cytokines are heterogeneous and not specific to senescent cells, these findings should be interpreted as evidence for possible modulation of senescence-associated markers rather than definitive effects on senescence burden. These observations support the use of multi-marker and functionally relevant endpoints in future clinical studies targeting biological ageing and cellular senescence.
Link: https://doi.org/10.1016/j.arr.2026.103224
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