The effects of graded calorie restriction XVII: Multitissue metabolomics reveals synthesis of carnitine and NAD, and tRNA charging as key pathways
Libia Alejandra García-Flores, Cara L. Green, Sharon E. Mitchell, Daniel Promislow, David Lusseau, Alex Douglas, John R. Speakman
Abstract
Significance Caloric restriction (CR) increases life and health span, but our understanding of the evolutionary basis of the effect remains unclear. For many years, the disposable soma hypothesis provided the main evolutionary explanation, suggesting animals under restriction divert resources away from reproduction toward somatic maintenance. This idea was recently challenged by the “clean cupboards” hypothesis, suggesting life extension under CR is a coincidental by-product of energy conservation. This paper tests between these ideas by looking for common signatures in the metabolomic response across multiple tissues to graded CR levels in mice. There was no evidence for widespread increases in somatic protection but instead largely idiosyncratic responses in individual tissues. The common pathways identified appeared more consistent with the clean cupboards hypothesis.