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Bioenergetic basis for the increased fatigability with ageing.


Maximus Peto’s Commentary

These researchers compared changes in exercise metabolites in young and old humans and found some very high correlations between the age-related increase in power loss during exercise and several metabolites (including intracellular pH, phosphate, and diprotonated phosphate). This makes me wonder: what age-related, stable, accumulating damage could be causing this apparent failure to clear these muscle contraction metabolites in aged human muscle?


Bioenergetic basis for the increased fatigability with ageing.
J Physiol. 2019 Oct;597(19):4943-4957.
Sundberg CW, Prost RW, Fitts RH, Hunter SK
DOI: 10.1113/JP277803
PubMed publication date (edat): 4/25/2019

Abstract

The present study aimed to determine whether the increased fatigability in old adults during dynamic exercise is associated with age-related differences in skeletal muscle bioenergetics. Phosphorus nuclear magnetic resonance spectroscopy was used to quantify concentrations of high-energy phosphates and pH in the knee extensors of seven young (22.7 ± 1.2 years; six women) and eight old adults (76.4 ± 6.0 years; seven women). Muscle oxidative capacity was measured from the phosphocreatine (PCr) recovery kinetics following a 24 s maximal voluntary isometric contraction. The fatiguing exercise consisted of 120 maximal velocity contractions (one contraction per 2 s) against a load equivalent to 20% of the maximal voluntary isometric contraction. The PCr recovery kinetics did not differ between young and old adults (0.023 ± 0.007 s-1  vs. 0.019 ± 0.004 s-1 , respectively). Fatigability (reductions in mechanical power) of the knee extensors was ∼1.8-fold greater with age and was accompanied by a greater decrease in pH (young = 6.73 ± 0.09, old = 6.61 ± 0.04) and increases in concentrations of inorganic phosphate, [Pi ], (young = 22.7 ± 4.8 mm, old = 32.3 ± 3.6 mm) and diprotonated phosphate, [H2 PO4 – ], (young = 11.7 ± 3.6 mm, old = 18.6 ± 2.1 mm) at the end of the exercise in old compared to young adults. The age-related increase in power loss during the fatiguing exercise was strongly associated with intracellular pH (r = -0.837), [Pi ] (r = 0.917) and [H2 PO4 – ] (r = 0.930) at the end of the exercise. These data suggest that the age-related increase in fatigability during dynamic exercise has a bioenergetic basis and is explained by an increased accumulation of metabolites within the muscle.

PMID: 31018011
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Maximus Peto

Max Peto is a longevity researcher and founder of Long Life Labs. A biochemist by training, he studies the biochemistry of aging and longevity and has worked with research organizations such as SENS Research Foundation, Methuselah Foundation, BioAge Labs, Life Extension Foundation, and Ichor Therapeutics. His work at Long Life Labs is focused on empowering people to understand and manage the most critical factors for better health and longer life.

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