The effect of aging and calorie restriction on mitochondrial morphology and dynamic in oxidative and glycolytic skeletal muscles
Authors: Faitg Julie , Leduc‐Gaudet Jean Philippe , Reynaud Olivier , Gouspillou Gilles 
Published: June 2021

With aging, skeletal muscles progressively loose mass and function, a biological process known as sarcopenia. Recent data indicate that accumulation of mitochondrial dysfunction plays a major role in the development of sarcopenia and also suggested that alterations in mitophagy and mitochondrial dynamics/morphology may represent mechanisms causing this accumulation of dysfunctional mitochondria in the aged muscles. One most efficient lifestyle and non‐pharmacological intervention to attenuate sarcopenia in rodents is calorie restriction (CR). The hypothesis currently put forward to explain the protective and “anti‐aging” effects of caloric restriction is that CR would attenuate the effects of aging on mitochondrial function. However, the specific effects of CR on many aspects of mitochondrial biology, especially in the aged muscle, remain unclear or unknown. In particular, the effects of aging and CR on skeletal muscle mitochondrial morphology and dynamics, which are known to impact mitochondrial function, remain largely under investigated. The objectives of the present study were (i) to investigate the effects of aging on mitochondrial morphology and dynamic in glycolytic and oxidative skeletal muscles, define whether CR can attenuate the effects of aging on mitochondrial morphology and (iii) determine the effects of CR and aging on the muscular phenotype.Three groups of male Sprague Dawley rats were studied: 1‐adult (9‐month‐old) ad‐libitum fed (AL) (A‐AL); 2‐old (21‐month‐old) AL fed (O‐AL) and; 3‐old (21‐month‐old) calorie restricted (CR; 40% calorie restricted for 13 months; O‐CR) rats. The morphology of SubSarcolemmal (SS) and InterMyoFibrillar (IMF) mitochondria was assessed using a 2‐dimensional transmission electron microscopy approach (TEM) in the oxidative soleus (SOL) and glycolytic white gastrocnemius (WG) muscles. Westernblot analyses were performed to assess the contents of proteins regulating mitochondrial dynamics (fusion protein: Mfn2; Fission proteins: Drp1 and Fis1) in the SOL and WG.CR attenuated the impact of aging on the muscle mass to body weight ratio (a marker of sarcopenia). The SOL of O‐AL rats displayed fragmented SS and IMF mitochondria vs A‐AL rats. CR attenuated this aging‐related fragmentation of SS and IMF mitochondria in the SOL. The WG of O‐AL rats displayed enlarged SS mitochondria and more complex and branched IMF mitochondria vs their younger counterparts. In the WG, CR did not attenuate the effects of aging on mitochondrial morphology. In the SOL, the contents of Drp1 and Fis1 were higher in O‐AL vs A‐AL rats. When compared to the SOL of Y‐AL rats, O‐CR rats displayed higher contents of both Drp1 and Mfn2. In the WG, the content of Mfn2 and Drp1 was higher in O‐AL vs A‐AL rats. No difference between O‐CR and A‐AL rats were observed for proteins regulating mitochondrial dynamics.Taken altogether, our results indicate that the effects of aging and calorie restriction on mitochondrial morphology and dynamic are complex and muscle‐specific.Support or Funding InformationThis work was funded by grants from the Natural Sciences and Engineering Council of Canada (NSERC; #RGPIN‐2014‐04668), the Quebec Research Network on Aging and the FQRS (FRQS‐35184) awarded to Gilles Gouspillou. Jean‐Philippe Leduc‐Gaudet is supported by a CIHR Vanier Doctoral Scholarship.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.