Pathophysiological Mechanisms Explaining the Association Between Low Skeletal Muscle Mass and Cognitive Function.
J Gerontol A Biol Sci Med Sci
; 77(10): 1959-1968, 2022 10 06.
Article
en En
| MEDLINE
| ID: mdl-35661882
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.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Cognición
/
Músculo Esquelético
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
J Gerontol A Biol Sci Med Sci
Asunto de la revista:
GERIATRIA
Año:
2022
Tipo del documento:
Article