age-associated changes in skeletal muscle
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Introduction
Skeletal muscle undergoes change with aging.
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) fibers
- loss of fast-twitch (type 2) fibers
- slower musccle 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://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/33303683 https://science.sciencemag.org/content/371/6528/eabc8059