Cellular and Functional Mechanisms Underlying Muscle Aging and Associated Diseases
Daniel Béchet, PhD
Unité de Nutrition Humaine/ Clermont Université, France
One of the most dramatic effects of increasing age is the atrophy of skeletal muscle, referred to as sarcopenia, which is predictive of all-cause mortality in the elderly. This presentation presents an overview of human studies of sarcopenia and describes findings from the PROOF cohort, which compared three groups --“healthy aging,” metabolic syndrome and hypertension-- to identify potential biomarkers for muscle chronological aging in humans.
- Muscle cells have no regenerative ability, leading to increasing loss with age.
- There is a 1-2% annual loss of muscle mass after the age of 50 years; however, the prevalence of sarcopenia varies from 13 to 24% of adults over 60 years of age, and > 50% after 80 years.
- Consequences of sarcopenia include: loss of strength, mobility, decreased energy metabolism, increased insulin resistance, lower protein (amino acid) reserves; an overall loss of health span.
- In a study to better understand the mechanisms of muscle aging: The PROOF cohort consisted of 1011 subjects (402 men, 609 women) aged 65 at inclusion date (2001); at 17-year follow up (now aged 82) with exams every 2 years. Exams included: anthropometric data, blood tests, blood pressure, heart monitors, cognitive performance, and biopsy of thigh muscle to apply “omics” and histological evaluation of thigh muscle biopsies.
- Researchers identified muscle fiber-type specific alterations and several potential biomarkers of aging:
- Atrophy of type-II muscle fibers, (flattening) in myofiber shape, increased lipid droplets, increased fibrosis of the extracellular matrix, and decreased capillaries.
- In men, healthy aging is associated with the presence of more perimysium (bundles of myofibers surrounding muscle) which preserves muscle shape despite atrophy.
- With chronological aging, profiles among gene pathways and proteins showed substantial alterations in muscle proteins involved in key metabolic pathways, myofibril remodeling, cytoskeleton organization and mechanisms of cytoprotection and cytodetoxification.
- Next, the researchers will address the question of why there is so much variation in biological aging.
These human studies offer important information about how muscle fibers change –physically and metabolically- with age. Improving our understanding of the factors influencing sarcopenia in people will also improve understanding of similar processes in companion animals.