Calorie Restriction Improves Stem Cell Function

Researchers here briefly review the ability of calorie restriction to improve stem cell function in various different tissues over the course of aging. This is thought to be one of the ways in which the practice of calorie restriction slows aging, quite significantly in short-life species, and much less so in longer-lived species. Since the short-term metabolic changes, and benefits to health, produced by calorie restriction are quite similar across mammals of different life spans, it remains an open question as to exactly why life expectancy is only modestly affected in long-lived species. Calorie restriction induces sweeping changes in near every aspect of cellular metabolism, and neither metabolism nor the effects of calorie restriction are completely mapped and understood. It will be a while yet before the research community has answers to the deeper questions about species differences in the long-term benefits produced by calorie restriction.

One of the most impactful and reproducible interventions that can slow down age-associated pathologies is calorie restriction (CR). CR is an intervention to prolong longevity, where the number of calories consumed is decreased but sufficient nutrition is maintained. Initially seen in a rodent study in 1935, recent findings have demonstrated its beneficial effect in mammals and primates. It has been thought that these advantages are mediated through stem cell proliferation and perseveration of stem cell activity, thus functioning as a regenerative therapy. Therefore, a thorough understanding of the mechanism, regulation, and signalling molecules underlying the advantages of CR for specific stem cells, such as muscle stem cells, intestinal epithelium stem cells, hematopoietic stem cells (HSCs) and hair follicle stem cells, would help in determining specific pharmacological and dietary intervention for regenerative therapy in the future. In addition, the structural and functional modifications observed can provide a more complete understanding of the numerous CR effects and thus be useful in therapy consideration.

One of the characteristics seen in age-related pathologies is stem cell exhaustion. Here, we review the various impacts of CR on mammalian health mediated through stem cell potency in various tissues. In the skeletal muscle, CR acts as an anti-inflammatory agent and increases the presence of satellite cells endogenously to improve regeneration, thus causing a metabolic shift to oxidation to meet oxygen demand. In the intestinal epithelium, CR suppresses the mechanistic target of rapamycin complex 1 (mTORC1) signalling in Paneth cells to shift the stem cell equilibrium towards self-renewal at the cost of differentiation. In haematopoiesis, CR prevents deterioration or maintains the function of HSCs depending on the genetic variation of the mice. In skin and hair follicles, CR increases the thickness of the epidermis and hair growth and improves hair retention through stem cells. CR mediates the proliferation and self-renewal of stem cells in various tissues, thus increasing its regenerative ability.


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