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

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.

Low lysophosphatidylcholine induces skeletal muscle myopathy that is aggravated by high‐fat diet feeding

“…[12][13][14] Evidence suggests that skeletal muscle lipid composition is robustly altered in multiple examples of skeletal muscle myopathy. 6,15,16 Indeed, several studies from our group and others provide evidence that overexpression or deletion of lipid-synthesizing enzymes can cause contractile defects in skeletal muscle. [17][18][19][20][21][22] The purpose of this study was to understand whether alterations in skeletal muscle lipids can explain the contractile dysfunction associated with obesity.…”

“…One possible cause is the altered muscle lipid milieu observed with obesity and/or type 2 diabetes 12–14 . Evidence suggests that skeletal muscle lipid composition is robustly altered in multiple examples of skeletal muscle myopathy 6,15,16 . Indeed, several studies from our group and others provide evidence that overexpression or deletion of lipid‐synthesizing enzymes can cause contractile defects in skeletal muscle 17–22 …”

Sarcopenia and Muscle Aging: A Brief Overview

“…However, the difficulty in obtaining muscle biopsies from those suffering from muscle atrophy may mean we must develop non-invasive or minimally invasive methods. For instance, fluxomics which can measure markers of muscle protein synthetic rate from saliva, urine, or blood of human patients and magnetic resonance spectroscopy, which monitors mitochondrial oxidative capacity, may be suitable methods for patients suffering from sarcopenia [137][138][139][140]. In addition, longitudinal monitoring studies spanning age, gender, and race have to be done to find early predictive biomarkers for the risk of sarcopenia.…”

Eat like an athlete: insights of sports nutrition science to support active aging in healthy older adults

“…In older people, higher concentrations of muscle PCr are associated with greater muscle volume and greater peak knee extensor power [34] while, conversely, sarcopenic older adults exhibit a lower muscle PCr content compared to non-sarcopenic controls [34]. Older adults exhibit greater increases in LBM [35,36], muscle thickness [37], and strength [35,36] during resistance training (3 × per week) [38] when supplementing with creatine (3-5 g/day).…”