Exercise intolerance and rapid skeletal muscle energetic decline in human age-associated frailty.
Aged
Aged, 80 and over
Energy Metabolism
Exercise
/ physiology
Female
Frail Elderly
Frailty
/ metabolism
Heart Failure
/ metabolism
Humans
Lower Extremity
/ pathology
Magnetic Resonance Imaging
Male
Middle Aged
Mitochondria
/ metabolism
Muscle, Skeletal
/ metabolism
Oxygen Consumption
/ physiology
Phosphates
/ metabolism
Aging
Bioenergetics
Mitochondria
Journal
JCI insight
ISSN: 2379-3708
Titre abrégé: JCI Insight
Pays: United States
ID NLM: 101676073
Informations de publication
Date de publication:
15 10 2020
15 10 2020
Historique:
received:
12
06
2020
accepted:
09
09
2020
pubmed:
18
9
2020
medline:
19
5
2021
entrez:
17
9
2020
Statut:
epublish
Résumé
BACKGROUNDPhysical frailty in older individuals is characterized by subjective symptoms of fatigue and exercise intolerance (EI). Objective abnormalities in skeletal muscle (SM) mitochondrial high-energy phosphate (HEP) metabolism contribute to EI in inherited myopathies; however, their presence or link to EI in the frail older adult is unknown.METHODSHere, we studied 3 groups of ambulatory, community-dwelling adults with no history of significant coronary disease: frail older (FO) individuals (81 ± 2.7 years, mean ± SEM), nonfrail older (NFO) individuals (79 ± 2.0 years), and healthy middle-aged individuals, who served as controls (CONT, 51 ± 2.1 years). Lower extremity SM HEP levels and mitochondrial function were measured with 31P magnetic resonance (MR) techniques during graded multistage plantar flexion exercise (PFE). EI was quantified by a 6-minute walk (6MW) and peak oxygen consumption during cardiopulmonary testing (peak VO2).RESULTSDuring graded exercise, FO, NFO, and CONT individuals all fatigued at similar SM HEP levels, as measured by 31P-MR. However, FO individuals fatigued fastest, with several-fold higher rates of PFE-induced HEP decline that correlated closely with shorter exercise duration in the MR scanner and with 6MW distance and lower peak oxygen consumption on cardiopulmonary testing (P < 0.001 for all). SM mitochondrial oxidative capacity was lower in older individuals and correlated with rapid HEP decline but less closely with EI.CONCLUSIONSeveral-fold faster SM energetic decline during exercise occurs in FO individuals and correlates closely with multiple measures of EI. Rapid energetic decline represents an objective, functional measure of SM metabolic changes and a potential new target for mitigating frailty-associated physical limitations.FUNDINGThis work was supported by NIH R21 AG045634, R01 AG063661, R01 HL61912, the Johns Hopkins University Claude D. Pepper Older Americans Independence Center P30AG021334, and the Clarence Doodeman Endowment in Cardiology at Johns Hopkins.
Identifiants
pubmed: 32941181
pii: 141246
doi: 10.1172/jci.insight.141246
pmc: PMC7605538
doi:
pii:
Substances chimiques
Phosphates
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIA NIH HHS
ID : P30 AG021334
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG063661
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL061912
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG045634
Pays : United States
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