age-associated changes in skeletal muscle
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Introduction
- skeletal muscle undergoes change with aging
- also see sarcopenia
Physiology
- age-associated changes occur in skeletal muscle, tendons, bursae, connective tissue & nerves[8]
- sarcopenia
- responsive to training
- parallels decrease in basal metabolic rate
- muscle tissue may be replaced with fibrous tissue
- loss in muscle strength exceeds loss in muscle mass
- loss least in diaphragm
- loss > in legs than arms
- rate of skeletal mass loss with age may he independent of level of physical activity
- increased fatigability
- small increase in number of slow-twitch (type 1) red fibers
- loss of fast-twitch (type 2) white fibers[17]
- slower muscle contraction
- lower peak strength of muscle contraction
- slower muscle relaxation[8]
- reduction in the number of motor units & fibers/unit
- infiltration of fat & lipofuscin into muscle bundles
- decreased myosin heavy chain synthesis
- adult skeletal muscle regenerates throughout life, but as the muscle ages, its ability to repair diminishes & eventually fails
- skeletal muscle cells are more likely to undergo apoptosis in response to physical inactivity[8]
- impairment is associated with an increase in tissue fibrosis
- age-related muscle stem cell dysfunction
- type 2 muscle fiber stem cells (MF2SC) from older humans contain higher levels of myostatin after exercise than MF2SC from younger individuals (& perhaps before exercise as well)[9]
- a balance between endogenous pSmad3 & active Notch controls regenerative capacity of muscle stem cells; deregulation of this balance in old muscle interferes with regeneration[5]
- Notch expression declines in old muscle & old muscle produces excessive TGF-beta (but not myostatin)
- TGF-beta induces Smad3 via TGFBR1
- endogenous Notch & Smad3 antagonize each other in control of satellite-cell proliferation
- activation of Notch blocks the TGF-beta-dependent upregulation of cyclin-dependent kinase inhibitors (CDKI) CDKN1A, CDKN1B, CDKN2A & CDKN2B
- whereas inhibition of Notch induces them
- in muscle stem cells, Notch activity determines binding of pSmad3 to promoters of CDKI genes CDKN1A, CDKN1B, CDKN2A & CDKN2B
- attenuation of TGF-beta/pSmad3 in old, injured muscle restores regeneration to satellite cells in vivo
- cyclic inhibition of STAT3 recruits muscle stem cells & promotes muscle repair[15]
- STAT3 activates transcription of genes in response to IL-6
- alterations in FGFR1 & p38-MAP kinase signaling affect age-related muscle stem cell dysfunction[10]
Radiology
- clinical relevance of abnormal imaging in the elderly is often unclear
Management
- diet & exercise programs may improve skeletal muscle function in the elderly (see sarcopenia)
Comparative biology
- age-related muscle stem cell dysfunction
- muscle stem cells (satellite cells) from aged mice tend to convert from a myogenic to a fibrogenic lineage as they begin to proliferate & this conversion is mediated by factors in the systemic environment of the old animals via Wnt signaling[6]
- p16ink4A silencing by RNA interference restores regenerative capacity of satellite cells in old mice[11]
- heterochronic parabioses, exposing old mice to factors present in young serum restores activation of Notch signalling & regenerative capacity of aged satellite cells[7]
- muscle transplantation studies in rats demonstrated that poor regeneration of muscles in old animals is a function of the host environment rather than an intrinsic defect in the host muscle stem cells[13]
- blood of young mice contains substances that reverse aging processes in heart muscle, skeletal muscle, & brain
- one of these substances is GDF11[14]
- PGE2 stimulates muscle stem cells & helps repair muscle damage[16]
- during aging, activity of 15-PGDH that degrades PGE2 progressively increases in muscle macrophages
- inhibiting macrophage 15-PGDH activity in older mice, by either genetic or pharmacologic interventions, raises levels of PGE2 & restores aged muscle, functionally & anatomically similar to muscle of young mice[16]
More general terms
Additional terms
- circulating plasma factors in cellular senescence
- muscular disease; myopathy
- sarcopenia
- skeletal muscle (voluntary muscle)
References
- ↑ Essentials of Clinical Geriatrics, 4th ed, Kane RL et al (eds) McGraw Hill, NY, 1999
- ↑ UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 29-Oct 2, 2004
- ↑ The Merck Manual of Geriatrics, 3rdh ed, Merck & Co, Rahway NJ, 2000
- ↑ Taffet GE, Physiology of Aging, In: Geriatric Medicine: An Evidence-Based Approach, 4th ed, Cassel CK et al (eds), Springer-Verlag, New York, 2003
- ↑ 5.0 5.1 Carlson ME, Hsu M, Conboy IM. Imbalance between pSmad3 and Notch induces CDK inhibitors in old muscle stem cells. Nature. 2008 Jul 24;454(7203):528-32 PMID: https://pubmed.ncbi.nlm.nih.gov/18552838
- ↑ 6.0 6.1 Brack AS et al, Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. Science. 2007 Aug 10;317(5839):807-10. PMID: https://pubmed.ncbi.nlm.nih.gov/17690295
- ↑ 7.0 7.1 Conboy IM et al, Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature. 2005 Feb 17;433(7027):760-4. PMID: https://pubmed.ncbi.nlm.nih.gov/15716955
- ↑ 8.0 8.1 8.2 8.3 8.4 Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010
Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013 - ↑ 9.0 9.1 McKay BR et al Myostatin is associated with age-related human muscle stem cell dysfunction FASEB J March 7, 2012 PMID: https://pubmed.ncbi.nlm.nih.gov/22403007
- ↑ 10.0 10.1 Bernet JD et al p38 MAPK signaling underlies a cell-autonomous loss of stem cell self-renewal in skeletal muscle of aged mice. Nature Medicine (2014) <PubMed> PMID: https://pubmed.ncbi.nlm.nih.gov/24531379 <Internet> http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.3465.html
- ↑ 11.0 11.1 Sousa-Victor P et al. Geriatric muscle stem cells switch reversible quiescence into senescence. Nature 2014 Feb 20; 506:316. PMID: https://pubmed.ncbi.nlm.nih.gov/24522534
- ↑ 12.0 12.1 Manini TM, Everhart JE, Anton SD et al Activity energy expenditure and change in body composition in late life. Am J Clin Nutr. 2009 Nov;90(5):1336-42. PMID: https://pubmed.ncbi.nlm.nih.gov/19740971
- ↑ 13.0 13.1 Carlson BM, Faulkner JA. Muscle transplantation between young and old rats: age of host determines recovery. Am J Physiol. 1989 Jun;256(6 Pt 1):C1262-6. PMID: https://pubmed.ncbi.nlm.nih.gov/273539
- ↑ 14.0 14.1 Sinha M et al. Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle. Science 2014 May 9; 344:649. PMID: https://pubmed.ncbi.nlm.nih.gov/24797481
- ↑ 15.0 15.1 Tierney MT, Aydogdu T, Sala D et al. STAT3 signaling controls satellite cell expansion and skeletal muscle repair. Nat Med. 2014. Oct;20(10):1182-6 PMID: https://pubmed.ncbi.nlm.nih.gov/25194572 PMCID: PMC4332844 Free PMC article
- ↑ 16.0 16.1 16.2 Palla AR, Ravichandran M, Wang YX et al. Inhibition of prostaglandin-degrading enzyme 15-PGDH rejuvenates aged muscle mass and strength. Science 2021 Jan 29; 371:eabc8059 PMID: https://pubmed.ncbi.nlm.nih.gov/33303683 https://science.sciencemag.org/content/371/6528/eabc8059
- ↑ 17.0 17.1 Horwath O, Moberg M, Edman S, Philp A, Apro W. Ageing Leads to Selective Type II Myofibre Deterioration and Denervation Independent of Reinnervative Capacity in Human Skeletal Muscle. Experimental Physiology. 2025;110(2):277-292. PMID: https://pubmed.ncbi.nlm.nih.gov/39466960 PMCID: PMC11782179