Effects of Aging and Caloric Restriction on Fiber Type Composition, Mitochondrial Morphology and Dynamics in Rat Oxidative and Glycolytic Muscles

Abstract

Aging is associated with a progressive decline in muscle mass and strength, a process known as sarcopenia. Evidence indicates that mitochondrial dysfunction plays a causal role in sarcopenia and suggests that alterations in mitochondrial dynamics/morphology may represent an underlying mechanism. Caloric restriction (CR) is among the most efficient nonpharmacological interventions to attenuate sarcopenia in rodents and is thought to exert its beneficial effects by improving mitochondrial function. However, CR effects on mitochondrial morphology and dynamics, especially in aging muscle, remain unknown. To address this issue, we investigated mitochondrial morphology and dynamics in the oxidative soleus (SOL) and glycolytic white gastrocnemius (WG) muscles of adult (9-month-old) ad libitum -fed (AL; A-AL), old (22-month-old) AL-fed (O-AL), and old CR (O-CR) rats. We show that CR attenuates the aging-related decline in the muscle-to-body-weight ratio, a sarcopenic index. CR also prevented the effects of aging on muscle fiber type composition in both muscles. With aging, the SOL displayed fragmented SubSarcolemmal (SS) and InterMyoFibrillar (IMF) mitochondria, an effect attenuated by CR. Aged WG displayed enlarged SS and more complex/branched IMF mitochondria. CR had marginal anti-aging effects on WG mitochondrial morphology. In the SOL, DRP1 (pro-fission protein) content was higher in O-AL vs YA-AL, and Mfn2 (pro-fusion) content was higher in O-CR vs A-AL. In the gastrocnemius, Mfn2, Drp1, and Fis1 (pro-fission) contents were higher in O-AL vs A-AL. CR reduced this aging-related increase in Mfn2 and Fis1 content. Overall, these results reveal for the first time that aging differentially impacts mitochondrial morphology and dynamics in different muscle fiber types, by increasing fission/fragmentation in oxidative fibers while enhancing mitochondrial size and branching in glycolytic fibers. Our results also indicate that although CR partially attenuates aging-related changes in mitochondrial dynamics in glycolytic fibers, its anti-aging effect on mitochondrial morphology is restricted to oxidative fibers.

Motoneuron deafferentation and gliosis occur in association with neuromuscular regressive changes during ageing in mice

“…Aged‐related changes in skeletal muscles have been reported in some murine models at histological and electrophysiological levels 68,80–84 (Hunter et al 85 . and McKinnon et al ., 86 as reviews).…”

“…Aged-related changes in skeletal muscles have been reported in some murine models at histological and electrophysiological levels 68,[80][81][82][83][84] (Hunter et al 85 and McKinnon et al, 86 as reviews). We examined the degree of histopathological alterations in different mouse muscles to assess the extent by which muscular changes could account for the impaired motor performance observed in old animals.…”

Drp1 knockdown induces severe muscle atrophy and remodelling, mitochondrial dysfunction, autophagy impairment and denervation

“…In the past decade, processes regulating mitochondrial dynamics have emerged as key players in the maintenance of mitochondrial size, localization and function. Further strengthening the interest surrounding mitochondrial dynamics in the field of muscle physiology, changes in mitochondrial dynamics and morphology have been reported in many conditions associated with muscle atrophy such as muscle ageing (Ibebunjo et al 2013;Leduc-Gaudet et al 2015;Tezze et al 2017;Zhou et al 2017;Faitg et al 2019), denervation-and immobilization-induced muscle atrophy (O'Leary et al 2013;Kang et al 2016), as well as cancer-and chemotherapy-induced muscle wasting (Barreto et al 2016;Brown et al 2017). However, the exact roles that mitochondrial dynamics, and particularly mitochondrial fission, play in skeletal muscle biology remains unclear.…”

“…2017; Faitg et al . 2019), denervation‐ and immobilization‐induced muscle atrophy (O'Leary et al . 2013; Kang et al .…”

Comprehensive histological investigation of age‐related changes in dermal extracellular matrix and muscle fibers in the upper lip vermilion

“…Decreases in MYH2 and MYH7 in older individuals resemble those seen for the soleus muscle [39] and suggest losses of MYH2 and MYH7 as causes of age‐dependent muscle fibre atrophy in the OOM. Although muscle fibres shift its type depending on muscle species and stimulations [39‐41], decreased MYH2 and MYH7 in combination with a constant MYH4 level suggests oxidative‐ to glycolytic‐type changes in OOM with age, because MYH2, −4 and −7 are myosin heavy chains for fast‐twitch oxidative glycolytic muscle fibres, fast‐twitch glycolytic muscle fibres and slow‐twitch oxidative fibres, respectively.…”