title: Skeletal muscle apoptotic signaling predicts thigh muscle volume and gait speed in community-dwelling older persons: an exploratory study.
abstract: BACKGROUND
  Preclinical studies strongly suggest that accelerated apoptosis in skeletal myocytes may be involved in the pathogenesis of sarcopenia. However, evidence in humans is sparse. In the present study, we investigated whether apoptotic signaling in the skeletal muscle was associated with indices of muscle mass and function in older persons.
  
  
  RESULTS
  Community-dwelling older adults were categorized into high-functioning (HF) or low-functioning (LF) groups according to their short physical performance battery (SPPB) summary score. Participants underwent an isokinetic knee extensor strength test and 3-dimensional magnetic resonance imaging of the thigh. Vastus lateralis muscle samples were obtained by percutaneous needle biopsy and assayed for the expression of a set of apoptotic signaling proteins. Age, sex, number of comorbid conditions and medications as well as knee extensor strength were not different between groups. HF participants displayed greater thigh muscle volume compared with LF persons. Multivariate partial least squares (PLS) regressions showed significant correlations between caspase-dependent apoptotic signaling proteins and the muscular percentage of thigh volume (R(2) = 0.78; Q(2) = 0.61) as well as gait speed (R(2) = 0.81; Q(2) = 0.56). Significant variables in the PLS model of percent muscle volume were active caspase-8, cleaved caspase-3, cytosolic cytochrome c and mitochondrial Bak. The regression model of gait speed was mainly described by cleaved caspase-3 and mitochondrial Bax and Bak. PLS predictive apoptotic variables did not differ between functional groups. No correlation was determined between apoptotic signaling proteins and muscle strength or quality (strength per unit volume).
  
  
  CONCLUSIONS
  Data from this exploratory study show for the first time that apoptotic signaling is correlated with indices of muscle mass and function in a cohort of community-dwelling older persons. Future larger-scale studies are needed to corroborate these preliminary findings and determine if down-regulation of apoptotic signaling in skeletal myocytes will provide improvements in the muscle mass and functional status of older persons.
authors.affiliation: Department of Aging and Geriatric Research, Institute on Aging, University of Florida, Gainesville, Florida, United States of America. emarzetti@live.com
authors.forename: Emanuele
authors.initials: E
authors.lastname: Marzetti
authors.forename: Hazel A
authors.initials: HA
authors.lastname: Lees
authors.forename: Todd M
authors.initials: TM
authors.lastname: Manini
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Buford
authors.forename: Juan M
authors.initials: JM
authors.lastname: Aranda
authors.forename: Riccardo
authors.initials: R
authors.lastname: Calvani
authors.forename: Giorgio
authors.initials: G
authors.lastname: Capuani
authors.forename: Michael
authors.initials: M
authors.lastname: Marsiske
authors.forename: Donovan J
authors.initials: DJ
authors.lastname: Lott
authors.forename: Krista
authors.initials: K
authors.lastname: Vandenborne
authors.forename: Roberto
authors.initials: R
authors.lastname: Bernabei
authors.forename: Marco
authors.initials: M
authors.lastname: Pahor
authors.forename: Christiaan
authors.initials: C
authors.lastname: Leeuwenburgh
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Wohlgemuth
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005684:Gait / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D008279:Magnetic Resonance Imaging; D008297:Male; D053580:Muscle Strength / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology*