Exercise and the Cisd2 Prolongevity Gene: Two Promising Strategies to Delay the Aging of Skeletal Muscle

Abstract

Aging is an evolutionally conserved process that limits life activity. Cellular aging is the result of accumulated genetic damage, epigenetic damage and molecular exhaustion, as well as altered inter-cellular communication; these lead to impaired organ function and increased vulnerability to death. Skeletal muscle constitutes ~40% of the human body’s mass. In addition to maintaining skeletal structure and allowing locomotion, which enables essential daily activities to be completed, skeletal muscle also plays major roles in thermogenesis, metabolism and the functioning of the endocrine system. Unlike many other organs that have a defined size once adulthood is reached, skeletal muscle is able to alter its structural and functional properties in response to changes in environmental conditions. Muscle mass usually remains stable during early life; however, it begins to decline at a rate of ~1% year in men and ~0.5% in women after the age of 50 years. On the other hand, different exercise training regimens are able to restore muscle homeostasis at the molecular, cellular and organismal levels, thereby improving systemic health. Here we give an overview of the molecular factors that contribute to lifespan and healthspan, and discuss the effects of the longevity gene Cisd2 and middle-to-old age exercise on muscle metabolism and changes in the muscle transcriptome in mice during very old age.

An Examination of Lactobacillus paracasei GKS6 and Bifidobacterium lactis GKK2 Isolated from Infant Feces in an Aged Mouse Model

“…In our preliminary test, an enhancement of Cisd2 gene expression in HEK293T cells was presented in GKK2 treatment but not in the GKS6 group (Figure S2). A persistent level of Cisd2 protected mitochondrial dysregulation and reduced DNA damage caused by oxidative stress; in addition, Cisd2 was involved in calcium homeostasis through the regulation of the calcium channels located on the endoplasmic reticulum and mitochondrial outer membranes [28][29][30]. ese affections maintain a better physical function in skeletal muscle, liver, and heart [31,32].…”

Cisd2 Protects the Liver from Oxidative Stress and Ameliorates Western Diet-Induced Nonalcoholic Fatty Liver Disease

“…Interestingly, some interventions seem to be associated with enhanced Cisd2 expression in mammals. For example, one of our recent studies has demonstrated that treadmill exercise for 56 days is able to significantly enhances Cisd2 expression using a Cisd2-luciferase reporter mouse model [ 34 ]. Moreover, voluntary exercise for four weeks is able to increase Cisd2 protein levels in the skeletal muscle and white adipose tissue of mice [ 35 ].…”

Rejuvenating the Aging Heart by Enhancing the Expression of the Cisd2 Prolongevity Gene

“…Many studies have demonstrated that exercising initiated at an age when deleterious alterations in the heart have already begun can attenuate cardiac fibrosis and collagen crosslinking that occur when an individual reaches an advanced age; these are important contributors to morbidity and mortality at an old age [ 27 , 28 ]. A human study also demonstrated that lifelong endurance training can preserve cardiac function at a level similar to that of young subjects, although the mechanism remains unknown [ 29 ].…”