Exercise Promotes Healthy Aging of Skeletal Muscle

Cartee, Gregory D.; Hepple, Russell T.; Bamman, Marcas M.; Zierath, Juleen R.

doi:10.1016/j.cmet.2016.05.007

Cited by 483Muscle Physiology and DisordersNutrition and Health in AgingMuscle metabolism and nutrition

Exercise Promotes Healthy Aging of Skeletal Muscle

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Cartee, Gregory D., Hepple, Russell T., Bamman, Marcas M., Zierath, Juleen R.·2016·Cell Metabolism

DOI 10.1016/j.cmet.2016.05.007PMC PMC5045036

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Abstract

Primary aging is the progressive and inevitable process of bodily deterioration during adulthood. In skeletal muscle, primary aging causes defective mitochondrial energetics and reduced muscle mass. Secondary aging refers to additional deleterious structural and functional age-related changes caused by diseases and lifestyle factors. Secondary aging can exacerbate deficits in mitochondrial function and muscle mass, concomitant with the development of skeletal muscle insulin resistance. Exercise opposes deleterious effects of secondary aging by preventing the decline in mitochondrial respiration, mitigating aging-related loss of muscle mass and enhancing insulin sensitivity. This review focuses on mechanisms by which exercise promotes "healthy aging" by inducing modifications in skeletal muscle.

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These adaptive responses increase tolerance and protect against subsequent stressors and are considered important for the health-promoting effects of exercise.
“These adaptive responses increase tolerance and protect against subsequent stressors and are considered important for the health-promoting effects of exercise (1, 2).”
From Skeletal muscle NOX4 is required for adaptive responses that prevent insulin resistance (2021) · cites this paper as [1]
The enhanced skeletal muscle insulin sensitivity after exercise affords metabolic flexibility and a means for replenishing glycogen to deal with subsequent bouts of intense physical activity.
“The enhanced skeletal muscle insulin sensitivity after exercise affords metabolic flexibility and a means for replenishing glycogen to deal with subsequent bouts of intense physical activity (1, 2).”
From Skeletal muscle NOX4 is required for adaptive responses that prevent insulin resistance (2021) · cites this paper as [1]
Exercise promotes glucose uptake and glycogen synthesis and increases insulin sensitivity, and this persists long after the cessation of exercise.
“Exercise promotes glucose uptake and glycogen synthesis and increases insulin sensitivity, and this persists long after the cessation of exercise (1, 2).”
From Skeletal muscle NOX4 is required for adaptive responses that prevent insulin resistance (2021) · cites this paper as [1]
Exercise results in skeletal muscle exposure to acute stresses that stimulate compensatory and adaptive physiological responses.
“Exercise results in skeletal muscle exposure to acute stresses that stimulate compensatory and adaptive physiological responses (1, 2).”
From Skeletal muscle NOX4 is required for adaptive responses that prevent insulin resistance (2021) · cites this paper as [1]
Exercise promotes contraction-induced and insulin-independent glucose uptake into muscle and increases muscle insulin sensitivity that persists long after cessation of exercise.
“Exercise not only promotes contraction-induced and insulin-independent glucose uptake into muscle, but also increases muscle insulin sensitivity that persists long after the cessation of exercise (1).”
From Skeletal muscle NOX4 is required for adaptive responses that prevent insulin resistance (2021) · cites this paper as [1]

A sedentary lifestyle accompanying aging, and aging itself, can promote the development of insulin resistance and type 2 diabetes independent of any changes in body weight.
“A sedentary lifestyle accompanying aging, and aging itself, can promote the development of insulin resistance and type 2 diabetes independent of any changes in body weight (1).”
From Skeletal muscle NOX4 is required for adaptive responses that prevent insulin resistance (2021) · cites this paper as [1]
Primary aging causes defects in mitochondrial energetics and loss of muscle mass, along with decreased physical activity and exercise.
“In skeletal muscle, primary aging causes defects in mitochondrial energetics and a loss of muscle mass, along with decreased physical activity and exercise [65].”
From Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis (2025) · cites this paper as [65]
Physical activity improves muscle and mitochondrial health in the elderly.
“Interestingly, physical activity, which is well known to improve muscle and mitochondrial health in the elderly [166], was recently shown to stimulate mitophagy [57,153,167,168] and increase Parkin expression in the skeletal muscles of rodents [153] and humans [57,168].”
From Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging (2021) · cites this paper as [166]
The beneficial effects of physical activity on muscle and mitochondrial health in older individuals might, at least in part, involve an upregulation of mitophagy.
“It is, therefore, possible that the beneficial effects of physical activity on muscle and mitochondrial health in older individuals [166] might, at least in part, involve an upregulation of mitophagy.”
From Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging (2021) · cites this paper as [166]
Physical activity has established benefits on mitochondrial efficiency in aged skeletal muscle.
“The established benefits of physical activity on mitochondrial efficiency in aged skeletal muscle2,47,59”
From Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities (2019) · cites this paper as [2]

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The combination of sport and sport-specific diet is associated with characteristics of gut microbiota: an observational study
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Weight management and physical activity throughout the cancer care continuum
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Lifelong physical activity is associated with promoter hypomethylation of genes involved in metabolism, myogenesis, contractile properties and oxidative stress resistance in aged human skeletal muscle
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Skeletal muscle NOX4 is required for adaptive responses that prevent insulin resistance
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Healthy aging and muscle function are positively associated with NAD+ abundance in humans
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The Interplay between Mitochondrial Morphology and Myomitokines in Aging Sarcopenia
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Hormones, Metabolism and the Benefits of Exercise
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Authors: Cartee, G. D., Hepple, R. T., Bamman, M. M., & Zierath, J. R.
Affiliations: University of Michigan (US)
McGill University Health Centre (CA)
University of Alabama at Birmingham (US)
University of Copenhagen (DK)
Corresponding author: Zierath, Juleen R.
ORCID: Cartee, Gregory D.
Hepple, Russell T.
Bamman, Marcas M.
Zierath, Juleen R.
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2016-06
Volume: 23
Issue: 6
Pages: 1034-1047
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2016.05.007
PMC: PMC5045036
OpenAlex: W2429359053
Cited by: 483
References: 181
Citations by year: 2026: 40 · 2025: 49 · 2024: 37 · 2023: 53 · 2022: 51 · 2021: 69 · 2020: 59 · 2019: 52 · 2018: 44 · 2017: 27 · 2016: 2
FWCI: 3.77
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 378 d)
Locations: Cell Metabolism (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders: Novo Nordisk Fonden (NNF14OC0011493)
National Institute on Aging (R01AG010026)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK071771, P30DK020572, P30DK020541, P30DK079626)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
Keywords: physical activity, healthy aging, skeletal muscle, primary aging, secondary aging, mitochondrial function, mitochondrial respiration, muscle mass loss, insulin resistance, insulin sensitivity
MeSH terms: Aging, Humans, Insulin, Mitochondria, Exercise, Muscle, Skeletal

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Exercise Promotes Healthy Aging of Skeletal Muscle

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