Please use this identifier to cite or link to this item: https://doi.org/10.1093/gerona/glac121
Title: Pathophysiological Mechanisms Explaining the Association Between Low Skeletal Muscle Mass and Cognitive Function
Authors: Oudbier, Susanne Janette
Goh, Jorming 
Looijaard, Stephanie Marcella Leonie Maria
Reijnierse, Esmee Marielle
Meskers, Carolus Gerardus Maria
Maier, Andrea Britta 
Keywords: Science & Technology
Life Sciences & Biomedicine
Geriatrics & Gerontology
Gerontology
Dementia
Inflammation
Insulin
Myokines
ALZHEIMERS-DISEASE
INSULIN-RESISTANCE
MITOCHONDRIAL DYSFUNCTION
NEUROTROPHIC FACTOR
OXIDATIVE STRESS
ADIPOSE-TISSUE
OLDER-ADULTS
BRAIN
PROTEIN
INTERLEUKIN-6
Issue Date: 6-Jun-2022
Publisher: OXFORD UNIV PRESS INC
Citation: Oudbier, Susanne Janette, Goh, Jorming, Looijaard, Stephanie Marcella Leonie Maria, Reijnierse, Esmee Marielle, Meskers, Carolus Gerardus Maria, Maier, Andrea Britta (2022-06-06). Pathophysiological Mechanisms Explaining the Association Between Low Skeletal Muscle Mass and Cognitive Function. JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES 77 (10) : 1959-1968. ScholarBank@NUS Repository. https://doi.org/10.1093/gerona/glac121
Abstract: Low skeletal muscle mass is associated with cognitive impairment and dementia in older adults. This review describes the possible underlying pathophysiological mechanisms: systemic inflammation, insulin metabolism, protein metabolism, and mitochondrial function. We hypothesize that the central tenet in this pathophysiology is the dysfunctional myokine secretion consequent to minimal physical activity. Myokines, such as fibronectin type III domain containing 5/irisin and cathepsin B, are released by physically active muscle and cross the blood-brain barrier. These myokines upregulate local neurotrophin expression such as brain-derived neurotrophic factor (BDNF) in the brain microenvironment. BDNF exerts anti-inflammatory effects that may be responsible for neuroprotection. Altered myokine secretion due to physical inactivity exacerbates inflammation and impairs muscle glucose metabolism, potentially affecting the transport of insulin across the blood-brain barrier. Our working model also suggests other underlying mechanisms. A negative systemic protein balance, commonly observed in older adults, contributes to low skeletal muscle mass and may also reflect deficient protein metabolism in brain tissues. As a result of age-related loss in skeletal muscle mass, decrease in the abundance of mitochondria and detriments in their function lead to a decrease in tissue oxidative capacity. Dysfunctional mitochondria in skeletal muscle and brain result in the excessive production of reactive oxygen species, which drives tissue oxidative stress and further perpetuates the dysfunction in mitochondria. Both oxidative stress and accumulation of mitochondrial DNA mutations due to aging drive cellular senescence. A targeted approach in the pathophysiology of low muscle mass and cognition could be to restore myokine balance by physical activity.
Source Title: JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
URI: https://scholarbank.nus.edu.sg/handle/10635/234867
ISSN: 1079-5006
1758-535X
DOI: 10.1093/gerona/glac121
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