Aging and muscle: a neuron's perspective

Age-related muscle weakness causes a staggering economic, public, and personal burden. Most research has focused on internal muscular mechanisms as the root cause to strength loss. Here, we briefly discuss age-related impairments in the brain and peripheral nerve structures that may theoretically lead to muscle weakness in old age.

Neuronal atrophy in the brain is accompanied by electrical noise tied to declines in dopaminergic neurotransmission that degrades communication between neurons. Additionally, sensorimotor feedback loops that help regulate corticospinal excitability are impaired. In the periphery, there is evidence for motor unit loss, axonal atrophy, demyelination caused by oxidative damage to proteins and lipids, and modified transmission of the electrical signal through the neuromuscular junction.

Recent evidence clearly indicates that muscle weakness associated with aging is not entirely explained by classically postulated atrophy of muscle. In this issue, which focuses on 'Ageing: Biology and Nutrition' we will highlight new findings on how nervous system changes contribute to the aging muscle phenotype. These findings indicate that the ability to communicate neural activity to skeletal muscle is impaired with advancing age, which raises the question of whether many of these age-related neurological changes are mechanistically linked to impaired performance of human skeletal muscle. Collectively, this work suggests that future research should explore the direct link of these 'upstream' neurological adaptions and onset of muscle weakness in elders. In the long term, this new focus might lead to novel strategies to attenuate the age-related loss of muscle strength.