Older adults with sarcopenia have distinct skeletal muscle phosphodiester, phosphocreatine, and phospholipid profiles

James Matthew Hinkley,Bret H Goodpaster,Paul M Coen,Rick B Vega,Bennett P Greenwood,Emily Y Chen,Fanchao Yi,Valerie Bussberg,Robert A Standley,Vladimir V Tolstikov,Niven R Narain,Heather H Cornnell,Michael A Kiebish

doi:10.1111/acel.13135

James Matthew Hinkley, Bret H Goodpaster + Show 11 more

Open Access

https://doi.org/10.1111/acel.13135

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Abstract

The loss of skeletal muscle mass and function with age (sarcopenia) is a critical healthcare challenge for older adults. 31‐phosphorus magnetic resonance spectroscopy (31P‐MRS) is a powerful tool used to evaluate phosphorus metabolite levels in muscle. Here, we sought to determine which phosphorus metabolites were linked with reduced muscle mass and function in older adults. This investigation was conducted across two separate studies. Resting phosphorus metabolites in skeletal muscle were examined by 31P‐MRS. In the first study, fifty‐five older adults with obesity were enrolled and we found that resting phosphocreatine (PCr) was positively associated with muscle volume and knee extensor peak power, while a phosphodiester peak (PDE2) was negatively related to these variables. In the second study, we examined well‐phenotyped older adults that were classified as nonsarcopenic or sarcopenic based on sex‐specific criteria described by the European Working Group on Sarcopenia in Older People. PCr content was lower in muscle from older adults with sarcopenia compared to controls, while PDE2 was elevated. Percutaneous biopsy specimens of the vastus lateralis were obtained for metabolomic and lipidomic analyses. Lower PCr was related to higher muscle creatine. PDE2 was associated with glycerol‐phosphoethanolamine levels, a putative marker of phospholipid membrane damage. Lipidomic analyses revealed that the major phospholipids, (phosphatidylcholine, phosphatidylethanolamine, and phosphatidylglycerol) were elevated in sarcopenic muscle and were inversely related to muscle volume and peak power. These data suggest phosphorus metabolites and phospholipids are associated with the loss of skeletal muscle mass and function in older adults.

Highlights

The population of older adults will more than double to 98 million by 2050 and represents a major healthcare challenge (Olshansky, Goldman, Zheng, & Rowe, 2009)
Resting phosphorus metabolites play a significant role in skeletal muscle health by influencing various physiological processes, including providing high-energy phosphates for contractile activity or structural stability to phospholipid-dense cellular membranes. 31-phosphorus magnetic resonance spectroscopy (31P-MRS) is an important tool to assess in vivo phosphorus metabolites and has been used to study skeletal muscle in aging and obesity
Despite other reports linking phosphorus metabolites with insulin sensitivity (Ripley et al, 2018; Szendroedi et al, 2011), we found that type 2 diabetes status did not influence the in vivo metabolic phenotype, and all subjects were grouped for correlative analyses

Summary

Introduction

The population of older adults will more than double to 98 million by 2050 and represents a major healthcare challenge (Olshansky, Goldman, Zheng, & Rowe, 2009). Previous reports have shown dysregulation of resting in vivo phosphorus metabolites under pathological conditions, including obesity, type 2 diabetes, spinal cord injury, and muscular dystrophy, and appear to be linked to clinical measures of glycemic control and body composition (Hooijmans et al, 2017; McCully, Mulcahy, Ryan, & Zhao, 2011; Ripley et al, 2018; Szendroedi et al, 2011). While resting phosphorus metabolites appear to be linked to clinical endpoints that are critical for metabolic health, it is unclear how these metabolites relate to muscle mass and function in older adults

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