Calorie Restriction Slows the Aging of Stem Cells in Subcutaneous Fat

The practice of calorie restriction is well known to slow aging, though the effects on life span are much larger in short-lived species. In humans calorie restriction is demonstrated to be beneficial to long-term health, certainly on a par with the results obtained from maintenance of physical fitness. Calorie restriction has noteworthy effects on the distribution and biochemistry of fat tissue. Researchers here report that one aspect of this outcome is a slowing of age-related changes in adult stem cells associated with subcutaneous fat.

With advancing age, there is a gradual loss of subcutaneous adipose tissue volume, leading to diminished glucose and lipid uptake. This phenomenon is known as "lipid overflow hypothesis," which results in the ectopic deposition of lipids in muscles and the liver, ultimately contributing to the development of insulin resistance. Long-term calorie restriction (CR) has been found to result in reduced adipocyte size and a beneficial remodeling of body fat composition, shifting away from visceral white adipose tissue towards subcutaneous white adipose tissue. This shift is significant as subcutaneous fat tends to have positive effects on aging and obesity, whereas visceral is associated with detrimental health outcomes.

Adipose-derived stem cells (ASCs) are crucial for tissue regeneration, but aging diminishes their stemness and regeneration potential. Aging is associated with increased adipose tissue fibrosis but no significant change in adipocyte size was observed with age. Long term caloric restriction failed to prevent fibrotic changes but resulted in significant decrease in adipocytes size. Aged subcutaneous ASCs displayed an increased production of reactive oxygen species (ROS). Using mitochondrial membrane activity as an indicator of stem cell quiescence and senescence, we observed a significant decrease in quiescence ASCs with age exclusively in the subcutaneous adipose depot. In addition, aged subcutaneous adipose tissue accumulated more senescent ASCs having defective autophagy activity. However, long-term caloric restriction leads to a reduction in mitochondrial activity in ASCs. Furthermore, caloric restriction prevents the accumulation of senescent cells and helps retain autophagy activity in aging ASCs. These results suggest that caloric restriction and caloric restriction mimetics hold promise as a potential strategy to rejuvenate the stemness of aged ASCs.


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