Hepple 2014 Abstract MiP2014
|Denervation modulates mitochondrial function when aging muscle atrophy becomes severe: implications for therapeutic intervention.|
Aging of skeletal muscle is associated with progressive atrophy, reaching clinically relevant thresholds in terms of weakness, mobility impairment and physical frailty in a significant fraction of individuals ≥80 y of age. Amongst the factors posited to be involved, mitochondrial alterations are implicated in the atrophy of aging muscle through recruitment of mitochondrial-mediated pathways of apoptosis and proteolysis. However, denervation is also known to recruit these same mitochondrial pathways. In view of the sporadic denervation that occurs in aging muscle, consideration of denervation’s role in recruitment of mitochondrial atrophy pathways is essential to identify relevant therapeutic targets. As such, this presentation will review our current evidence from human skeletal muscle biopsies across a range of ages and physical activity levels, examining the impact of aging on mitochondrial function and the role played by denervation across this continuum. As will be demonstrated, skeletal muscle mitochondrial alterations in septuagenarian subjects appears to be a primary event unrelated to denervation, where an increased susceptibility to mitochondrial permeability transition persists even in physically active subjects. In contrast, octogenarian subjects exhibit denervation-induced modulation of mitochondrial reactive oxygen species emission, suggesting failed reinnervation rather than mitochondrial dysfunction as a more appropriate therapeutic target when aging muscle atrophy becomes most clinically relevant.
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style, mt-Medicine Pathology: Aging;senescence Stress:Cell death, Permeability transition, Oxidative stress;RONS, Mitochondrial disease Organism: Human Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Coupling state: OXPHOS
HRR: Oxygraph-2k Event: A3, Oral MiP2014
Dep Kinesiology, Dep Critical Care Medicine, McGill Univ Health Center - Meakins Christie Lab, Royal Victoria Hospital, Montreal, Canada. - [email protected]