Two Weeks of Reduced Activity Decreases Leg Lean Mass and Induces “Anabolic Resistance” of Myofibrillar Protein Synthesis in Healthy Elderly
Abstract
BACKGROUND: Alterations in muscle protein metabolism underlie age-related muscle atrophy. During periods of muscle disuse, muscle protein synthesis is blunted, and muscle atrophy occurs in young and old. The impact of a short reduction in physical activity on muscle protein metabolism in older adults is unknown. PURPOSE: The aim of this study was to investigate the impact of 14 days of reduced daily steps on fasted and fed-state rates of myofibrillar protein synthesis (MPS) to provide insight into the mechanisms for changes in muscle mass and markers of metabolic health. METHODS: Before and after 14 days of reduced daily step-count, 10 healthy older adults (age, 72 ± 1 y) underwent measures of insulin sensitivity, muscle strength, physical function, and body composition. Using a primed constant infusion of L-[ring-(13)C6]phenylalanine with serial muscle biopsies, basal, postabsorptive, and postprandial rates of MPS were determined before and after the 14-day intervention. RESULTS: Daily step-count was reduced by approximately 76% to 1413 ± 110 steps per day. Leg fat-free mass was reduced by approximately 3.9% (P < .001). Postabsorptive insulin resistance was increased by approximately 12%, and postprandial insulin sensitivity was reduced by approximately 43% after step reduction (P < .005). Concentrations of TNF-α and C-reactive protein were increased by approximately 12 and 25%, respectively, after step reduction (P < .05). Postprandial rates of MPS were reduced by approximately 26% after the intervention (P = .028), with no difference in postabsorptive rates. CONCLUSION: The present study demonstrates that 14 days of reduced steps in older adults induces small but measurable reductions in muscle mass that appear to be underpinned by reductions in postprandial MPS and are accompanied by impairments in insulin sensitivity and systemic inflammatory markers and postprandial MPS.
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Low physical activity is directly related to increased anabolic resistance and levels of CRP and pro-inflammatory cytokines in healthy individuals, breast cancer survivors, and patients with type 2 diabetes.
“Low physical activity, therefore, has been found to be directly related to increased anabolic resistance96 and levels of CRP and pro-inflammatory cytokine levels in healthy individuals97, as well as in breast cancer survivors98 and patients with type 2 diabetes99.”
From Chronic inflammation in the etiology of disease across the life span (2019) · cites this paper as [96]
Taking fewer steps lowers anabolic sensitivity to protein and reduces leg lean mass.
“We have shown that periods in which fewer steps are taken, as a model of inactivity but not outright muscle disuse, result in reductions in anabolic sensitivity to protein (3,4) and declines in leg lean mass (3).”
In the two step-reduction studies in older adults, there was no impact on muscle function (isometric strength or short physical performance battery score).
“Although there was no impact on muscle function (i.e. isometric strength or short physical performance battery score) in either study,56,57”
From Reduced physical activity in young and older adults: Metabolic and musculoskeletal implications (2019) · cites this paper as [56]
Significant muscle atrophy is seen with only 14 days of step reduction in both young and older adults; reported 1-4% losses in muscle mass are striking and concerning, considering that sarcopenic muscle loss is estimated to occur at approximately 0.8% per year.
“Significant muscle atrophy is seen with only 14 days of step reduction in both young and older adults;28,29,56 the reported 1–4% losses in muscle mass are both striking and concerning, considering that sarcopenic muscle loss is estimated to occur at ~0.8% per year.50”
From Reduced physical activity in young and older adults: Metabolic and musculoskeletal implications (2019) · cites this paper as [56]
The inactivity-induced anabolic resistance was accompanied by evidence of systemic low-grade inflammation (increased C-reactive protein and tumour necrosis factor-α).
“evidence of systemic low-grade inflammation (i.e. increased C-reactive protein and tumour necrosis factor-α)”
From Reduced physical activity in young and older adults: Metabolic and musculoskeletal implications (2019) · cites this paper as [56]
In the same older adults, feeding-induced stimulation of myofibrillar protein synthesis after ingestion of 25 g protein was blunted by ~26% after 14 days of step reduction.
“the feeding-induced stimulation of myofibrillar protein synthesis after ingestion of 25 g of protein was blunted by ~26% after the 14 days.”
From Reduced physical activity in young and older adults: Metabolic and musculoskeletal implications (2019) · cites this paper as [56]
In 10 healthy older adults (age 72 ± 1 year), 14 days of step reduction from ~6000/day to ~1500/day did not impact basal rates of myofibrillar protein synthesis.
“Although there was no impact of this step reduction on basal rates of myofibrillar protein synthesis”
From Reduced physical activity in young and older adults: Metabolic and musculoskeletal implications (2019) · cites this paper as [56]
The inactivity-induced anabolic resistance was accompanied by a loss of ~0.6 kg of leg fat-free mass in only 2 weeks.
“and a loss of ~0.6 kg of leg fat-free mass in only 2 weeks,56”
From Reduced physical activity in young and older adults: Metabolic and musculoskeletal implications (2019) · cites this paper as [56]
The inactivity-induced anabolic resistance was accompanied by progression of insulin resistance.
“This inactivity-induced anabolic resistance was also accompanied by the progression of insulin resistance”
From Reduced physical activity in young and older adults: Metabolic and musculoskeletal implications (2019) · cites this paper as [56]
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- Authors
- Breen, L., Stokes, K. A., Churchward-Venne, T. A., Moore, D. R., Baker, S. K., Smith, K., Atherton, P. J., & Phillips, S. M.
- Affiliations
- University of Birmingham (GB)
- University of Bath (GB)
- 1Department of Kinesiology (L.B., T.A.C.-V., D.R.M., S.M.P.), McMaster University, Hamilton, Ontario, Canada L8S 4K1
- McMaster University (CA)
- University of Nottingham (GB)
- Corresponding author
- Phillips, Stuart M.
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2013-06-01
- Volume
- 98
- Issue
- 6
- Pages
- 2604-2612
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W1997591046
- Cited by
- 395
- References
- 39
- Citations by year
- 2026: 20 · 2025: 23 · 2024: 28 · 2023: 39 · 2022: 34 · 2021: 55 · 2020: 42 · 2019: 31 · 2018: 35 · 2017: 19 · 2016: 27 · 2015: 24 · 2014: 13 · 2013: 4
- FWCI
- 13.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- Medical Research Council (MR/K00414X/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- reduced physical activity, myofibrillar protein synthesis, muscle atrophy, insulin resistance, insulin sensitivity, systemic inflammation, TNF-α, C-reactive protein, older adults, muscle protein metabolism, sarcopenia
- MeSH terms
- Aged, Amino Acids, Blood Glucose, Body Composition, C-Reactive Protein, Diet, Energy Metabolism, Female, Humans, Insulin Resistance, Leg, Male, Muscle Proteins, Myofibrils, Exercise, Ribosomal Protein S6 Kinases, 70-kDa
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