Plasma Biomarkers of Poor Muscle Quality in Older Men and Women from the Baltimore Longitudinal Study of Aging

Abstract

Aging is characterized by progressive decline in muscle mass, strength, and quality all of which contribute to functional impairment, falls, mobility disability, and frailty. Circulating factors may provide clues on the mechanisms for decline in muscle quality with aging. Characterizing the metabolic profile associated with reduced muscle quality in older persons could have important translational implications for the early identification of subjects at high risk of developing sarcopenia and the identification of targets for new preventive strategies and treatments. In a pilot cross-sectional, case-control study nested in the Baltimore Longitudinal Study on Aging, we compared circulating metabolites between 79 participants with low muscle quality ratio and 79 controls with high muscle quality, matched by age, sex, and height. The concentrations of 180 metabolites were determined by LC MS/MS, using the Biocrates p180 system, a targeted metabolomics approach. Participants with low muscle quality had significantly higher levels of leucine, isoleucine, tryptophan, serotonin, and methionine, while those with high muscle quality had significantly lower levels of putrescine and the selected phophatidylcholine (PCs) and lysoPCs. The results of this study open a new road for future investigations aimed at identifying new metabolic pathways involved in the decline of muscle quality with aging.

Plasma metabolomic profiling of a ketamine and placebo crossover trial of major depressive disorder and healthy control subjects

“…Targeted metabolites were extracted and concentrations were assessed using the AbsoluteIDQ kit p180 (Biocrates Life Science AG, Austria), following the manufacturer’s protocol for the API5500 LC-MS/MS System (AB SCIEX, USA) running with Analyst 1.5.2 software equipped with an electrospray ionization source, a Shimadzu CBM-20A command module, LC-20AB pump, and a Shimadzu SIL-20ACHT autosampler and a CTO-10Ac column oven heater, as previously described (Moaddel et al 2016). Briefly, 10 μl of plasma samples was pipetted onto a 96-well Biocrates kit, and samples were dried for 30 min.…”

“…This pathway is critical as it generates a range of metabolites that are involved in the interface of inflammatory/immune response and glutamatergic neurotransmission (Miller 2013). The two most important rate-limiting enzymes involved in the catabolism of Trp to Kyn are 2,3-dioxygenase (TDO), mainly expressed in the liver, and indoleamine 2,3-dioxygenase (IDO), with IDO1 mainly expressed in the blood, placenta, lungs, and brain and IDO2 mainly expressed in the brain (Moaddel et al 2016). IDO is upregulated during pro-inflammatory states induced by cytokines (IL-1β, IL-6, IFN-α, TNF-α) (Heisler and O’Connor 2015) and is a therapeutic target in depression (Dobos et al 2012).…”

Searching for a mitochondrial root to the decline in muscle function with ageing

“…Conversely, low BCAA levels are associated with impaired mitochondrial biogenesis and reduced energy production . Finally, isoleucine and leucine catabolism in muscle causes increased levels of NADH and FADH 2 , which are essential cofactors for ATP synthesis . Incidentally, glycerophospholipids—specifically a subset of phosphatidylcholines—were significantly lower levels in participants with low muscle quality compared with controls.…”

“…In order to better understand the mechanisms by which muscle quality declines with ageing, a matched (by sex, age, and height) nested case–control study was performed within the Baltimore Longitudinal Study of Aging, characterizing the plasma metabolic profile associated with low vs. high muscle quality in participants that were 60+ years old . In this study, muscle quality was defined as the ratio of muscle torque (assessed by isokinetic dynamometry) to muscle mass, which was estimated from the muscle cross‐sectional area of the mid‐thigh acquired by computed tomography.…”

AGS and NIA Bench‐to Bedside Conference Summary: Osteoporosis and Soft Tissue (Muscle and Fat) Disorders

“…Metabolomic and other omics biomarkers might also be useful. An analysis of data on older adults identified metabolites (including leucine, isoleucine, and tryptophan) associated with poor muscle quality and others (eg, low levels of putrescine) associated with good muscle quality . Epigenetic markers of sarcopenia (eg, markers of histone acetylation and methylation) are being explored because aging is associated with changes in epigenetic mechanisms and activity …”