4.0 Article

Caloric restriction attenuates the age-associated increase of adipose-derived stem cells but further reduces their proliferative capacity

Journal

AGE
Volume 33, Issue 2, Pages 107-118

Publisher

SPRINGER
DOI: 10.1007/s11357-010-9166-4

Keywords

Stem cells; Aging; Caloric restriction; Adipose tissue; Regeneration; Cancer

Funding

  1. National Heart, Lung, and Blood Institute [1R21HL092477]
  2. National Institutes of Health, under the National Heart Lung and Blood Institute [T32 HL 07936]

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White adipose tissue is a promising source of mesenchymal stem cells. Currently, little is known about the effect of age and caloric restriction (CR) on adipose-derived stem cells (ASC). This is important for three reasons: firstly, age and CR cause extensive remodeling of WAT; it is currently unknown how this remodeling affects the resident stem cell population. Secondly, stem cell senescence has been theorized as one of the causes of aging and could reduce the utility of a stem cell as a reagent. Thirdly, the mechanism by which CR extends lifespan is currently not known, one theory postulates that CR maintains the resident stem cell population in youthful fit state. For the purpose of this study, we define ASC as lineage negative (lin(-))/CD34(+(low))/CD31(-). We show that aging increases the abundance of ASC and the expression of Cdkn2a 9.8-fold and Isl1 60.6-fold. This would suggest that aging causes an accumulation of non-replicative ASC. CR reduced the percentage of ASC in the lin(-) SVF while also reducing colony forming ability. Therefore, CR appears to have anti-proliferative effects on ASC that may be advantageous from the perspective of cancer, but our data raises the possibility that it may be disadvantageous for regenerative medicine applications.

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