Mitochondrial Dysfunction Correlates with Aspects of Frailty in Old People

Researchers here measure mitochondrial function in older people and find that those with less functional mitochondria are more prone to physical aspects of frailty, such as loss of mobility resulting from muscle weakness. Sarcopenia, the loss of muscle mass and strength with age, may largely result from loss of muscle stem cell activity, and mitochondrial dysfunction with age may be an important contributing cause of stem cell decline. That said, all of the aspects of aging tend to move in unison in any one individual, and independent mechanisms of aging form a loosely interact web of cause and consequence. An observed correlation between any two aspects of aging doesn't necessarily imply direct and meaningful causation.

Slow gait and mobility decline are common in older age and are associated with adverse outcomes such as mobility disability, reduced quality of life, loss of autonomy in daily life activities, and mortality. Such a decline may arise from impairments in the central nervous system (CNS), musculoskeletal system, and metabolic systems. Previous findings suggest that age-related decline of mitochondrial function may contribute to loss of mobility. Compared to young adults, older adults have lower skeletal muscle oxidative capacity and higher metabolic cost of walking.

Proposed mechanisms underlying the relationship between mitochondrial dysfunction and mobility decline include impairments in energy production and energy utilization. Energy production can be impaired due to age-related decline of mitochondrial function, possibly through a combination of lack of energy, increased oxidative stress, oxidative damage to mitochondrial DNA and the complexes of the electron transport chain, and altered gene expression.

We examined 380 cognitively normal participants aged 60 and older who were well-functioning (gait speed ≥ 1.0 m/s) and free of Parkinson's disease and stroke at baseline and had data on baseline skeletal muscle oxidative capacity and one or more mobility assessments during an average 2.5 years. Muscle oxidative capacity was measured by phosphorus magnetic resonance spectroscopy as the post-exercise recovery rate of phosphocreatine (kPCr). Mobility was measured by four walking tests.

Lower baseline kPCr was associated with greater decline in all four mobility measures. Thus among initially well-functioning older adults, worse muscle mitochondrial function predicts mobility decline, and part of this longitudinal association is explained by decline in muscle strength and mass. Our findings suggest that worse mitochondrial function contributes to mobility decline with aging. The longitudinal relationship between skeletal muscle mitochondrial function and mobility decline appeared to be mediated by the change in thigh muscle strength, lean mass, and fat mass.


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