Aging-linked systemic lipid signature is reprogrammed by caloric restriction in rhesus monkeys

Caloric restriction (CR) without malnutrition delays aging in diverse species, including primates, with metabolic changes implicated in this process. To facilitate exploration of CR metabolism with aging, we developed a 15-minute LC-MS/MS metabolomics and lipidomics method, leveraging monophasic extractions and wide elution-strength solvents. We analyzed 494 plasma samples collected over 25 years from male and female rhesus monkeys (Macaca mulatta) on a Control or CR (30% restricted) diet. Quantitation of 359 biomolecules revealed that aging, followed by sex and diet, had the largest impact on metabolite abundances. In both sexes, aging was associated with significantly lower plasma levels of sphingomyelins (SMs) and higher levels of diglycerides (DGs) and triglycerides (TGs), each of which was opposed by CR. Sex dimorphism was evident by the increased abundance of phosphocholine (PC)-containing lipids in females. These results highlight the utility of a rapid metabolomics and lipidomics approach to elucidate complex biology in large-scale studies.