title: Aging augments the impact of influenza respiratory tract infection on mobility impairments, muscle-localized inflammation, and muscle atrophy.
abstract: Although the influenza virus only infects the respiratory system, myalgias are commonly experienced during infection. In addition to a greater risk of hospitalization and death, older adults are more likely to develop disability following influenza infection; however, this relationship is understudied. We hypothesized that upon challenge with influenza, aging would be associated with functional impairments, as well as upregulation of skeletal muscle inflammatory and atrophy genes. Infected young and aged mice demonstrated decreased mobility and altered gait kinetics. These declines were more prominent in hind limbs and in aged mice. Skeletal muscle expression of genes involved in inflammation, as well as muscle atrophy and proteolysis, increased during influenza infection with an elevated and prolonged peak in aged mice. Infection also decreased expression of positive regulators of muscle mass and myogenesis components to a greater degree in aged mice. Gene expression correlated to influenza-induced body mass loss, although evidence did not support direct muscle infection. Overall, influenza leads to mobility impairments with induction of inflammatory and muscle degradation genes and downregulation of positive regulators of muscle. These effects are augmented and prolonged with aging, providing a molecular link between influenza infection, decreased resilience and increased risk of disability in the elderly.
authors: UConn Center on Aging, University of Connecticut Health Center, Farmington, CT 06030, USA.|Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors: Jenna M
authors: JM
authors: Bartley
authors: UConn Center on Aging, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors: Sarah J
authors: SJ
authors: Pan
authors: UConn Center on Aging, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors: Spencer R
authors: SR
authors: Keilich
authors: UConn Center on Aging, University of Connecticut Health Center, Farmington, CT 06030, USA.|Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors: Jacob W
authors: JW
authors: Hopkins
authors: UConn Center on Aging, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors: Iman M
authors: IM
authors: Al-Naggar
authors: UConn Center on Aging, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors: George A
authors: GA
authors: Kuchel
authors: UConn Center on Aging, University of Connecticut Health Center, Farmington, CT 06030, USA.|Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors: Laura
authors: L
authors: Haynes
mesh_terms: D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D005684:Gait / Q000502:physiology; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D009980:Influenza A virus; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D009133:Muscular Atrophy / Q000378:metabolism / Q000473:pathology / Q000821:virology; D063806:Myalgia / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D009976:Orthomyxoviridae Infections / Q000378:metabolism / Q000473:pathology*
keywords: aging; disability; influenza; muscle atrophy; resilience