Aerobic Function in Aging Skeletal Muscle: From Molecular to Systemic Mechanisms
Sponsored by the APS Muscle Biology Group

The ability to sustain muscular exercise depends on the effective integration of oxygen transport to, and oxygen utilization by, skeletal muscle mitochondria. With advancing age the systems that determine this ability (such as the maximal rates of cardiac output, limb blood flow, mitochondrial oxidative phosphorylation) become progressively limited. These declines arise in molecular, mitochondrial and systemic functions that, in the extreme, limit the aged persons’ ability to maintain an adequate quality of life. With respect to skeletal muscle and aging, much attention is paid to the effects of sarcopenia and consequential effects on muscle power generation (158 citations on Pubmed¹), however, we contend, that relatively little attention is paid to the mechanisms of aerobic function decline (30 citations on Pubmed²) during senescence; naturally both of these are required for effective power generation that can be sustained for functionally meaningful durations. The proposed symposium will focus on the integration of age-related declines from multiple levels of investigation: the limitations to systemic function will be addressed from intramuscular molecular function to whole-muscle O₂ delivery, encompassing both cellular and integrative approaches. The first speaker, Dr. John Kowalchuk, will describe the “status of the problem”, illustrating the systemic limitations to exercise tolerance in senescent humans, with particular stress on the mediation of the non-steady-state responses of cardiovascular and aerobic skeletal muscle function. Following this, the talks will focus on progressive steps down the oxygen cascade from O₂ delivery, via the mitochondrion, to cell signaling. Dr. David Poole will present recent findings on how aging alters skeletal muscle vascular geometry and vascular control such that blood flow and oxygen delivery are impaired in aging. Dr. Kevin Short will then present how the decline in muscle oxidative phosphorylation with aging is related to reduced mitochondrial synthesis and mitochondrial dysfunction (resulting from mitochondrial DNA damage, oxidative damage and uncoupling). Finally, Dr. Frank Booth, will highlight the age-related impairment in various cellular signaling pathways in skeletal muscle and their effects on skeletal muscle regeneration. We aim, therefore, to highlight the current state of knowledge regarding impairment of exercise tolerance in healthy, but aged, humans, and to discuss how these relate to oxygen delivery, mitochondrial, and molecular limitations to aerobic function in aged skeletal muscle.

[¹ Search criteria: skeletal muscle AND aging AND sarcopenia (April 2005)]

[² Search criteria: skeletal muscle AND aging AND oxidative phosphorylation (April 2005)]