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

## TL;DR

This study shows that caloric restriction in rhesus monkeys reverses age-related changes in blood lipids and highlights sex differences in lipid profiles.

## Contribution

A new rapid metabolomics and lipidomics method was developed and applied to a large longitudinal primate study.

## Key findings

- Aging in rhesus monkeys is linked to lower sphingomyelins and higher diglycerides and triglycerides.
- Caloric restriction reversed these age-related lipid changes in both male and female monkeys.
- Sex differences were observed in phosphocholine lipid levels and glycerophospholipid abundance.

## Abstract

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.

Using a rapid metabolomics approach on longitudinally collected plasma from caloric restriction (CR) rhesus monkeys, this study reveals diet-, sex-, and age-specific lipid changes occurring over 30-years.

This study reports the development of a fast, high-throughput method suitable for large-scale studies with time-sensitive requirements.The concatenated approach allows for simultaneous, comprehensive detection of metabolite and lipid species that is equally effective for human and nonhuman primate biospecimens.Longitudinal metabolomics analysis quantified 359 metabolite and lipid features across 494 plasma samples and identified SM, DG, and TG signatures of aging that were opposed by CR.There is evidence for sex dimorphism in circulating lipids, including the saturation indices of PC and the abundance of glycerophospholipids.

This study reports the development of a fast, high-throughput method suitable for large-scale studies with time-sensitive requirements.

The concatenated approach allows for simultaneous, comprehensive detection of metabolite and lipid species that is equally effective for human and nonhuman primate biospecimens.

Longitudinal metabolomics analysis quantified 359 metabolite and lipid features across 494 plasma samples and identified SM, DG, and TG signatures of aging that were opposed by CR.

There is evidence for sex dimorphism in circulating lipids, including the saturation indices of PC and the abundance of glycerophospholipids.

Using a rapid metabolomics approach on longitudinally collected plasma from caloric restriction (CR) rhesus monkeys, this study reveals diet-, sex-, and age-specific lipid changes occurring over 30-years.