Abstract
Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein implicated in various functions, including metabolism, tissue regeneration, and functional homeostasis. SPARC/Sparc declines with ageing but increases with exercise. We aim to verify two hypotheses: (1) SPARC deficiency leads to an ageing-like phenotype (metabolic decline, muscle loss, etc.), and (2) SPARC overexpression would mimic exercise, counteract ageing, and improve age-related changes. Our mice experiments are divided into two parts. First, we explore the consequences of Sparc knockout (KO) and compare them to the ageing effects. We also observe the effects of exercise. In the second part, we study the effects of SPARC overexpression and compare them to the exercise benefits. At the end, we make an analysis of the results to point out the analogies between Sparc KO and the ageing-like phenotype on the one hand and make comparisons between SPARC overexpression and exercise in the context of exercise counteracting ageing. The measurements were mainly related to tissue weights, adiposity, metabolism, and muscle strength. The main findings are that Sparc KO reduced glucose tolerance, muscle glucose transporter expression, and abdominal adipose tissue weight but increased glycogen content in the muscle. SPARC overexpression increased muscle strength, muscle mass, and expressions of the muscle glucose transporter and mitochondrial oxidative phosphorylation but lowered the glycemia and the adiposity, especially in males. Collectively, these findings, and the data we have previously reported, show that Sparc KO mice manifest an ageing-like phenotype, whereas SPARC overexpression and exercise generate similar benefits. The benefits are towards counteracting both the SPARC deficiency-induced ageing-like phenotype as well as reversing the age-related changes. The potential applications of these findings are to build/optimize Sparc KO-based animal models of various health conditions and, on the other hand, to develop therapies based on introducing SPARC or targeting SPARC-related pathways to mimic exercise against age-related and metabolic disorders.
Highlights
As Sparc decreases with ageing, and exercise both increases Sparc/secreted protein acidic and rich in cysteine (SPARC) [10,14] and counteracts ageing, we suggest that the ageing results and exercise benefits are mediated, at least in part, by SPARC, especially in the way that age-related alterations in skeletal muscle progenitor cells are linked to SPARC, for instance [15]
To highlight the similarities between ageing effects and Sparc KO, our data, as well as the results we previously reported from the same set of Sparc KO experiment mice [11], showed that Sparc KO led to an ageing-like phenotype, including muscle loss, grip power reduction, lower oxidative phosphorylation, glucose intolerance, and reduced glucose transport into muscles
Sarcopenia, for which ageing represents a risk factor [37], is characterized by a generalized loss of muscle mass and strength [49]. This clinical definition fits with the Sparc KO phenotype as we reported previously [11] on the signs that are related to both ageing and a sedentary lifestyle [39], which are impacted by myokines, including
Summary
With the improvement of the healthcare system and the decline of infectious diseases (vaccines, therapies, etc.), life expectancy has increased significantly over the past 50 years [1], which has enhanced the elderly population. This makes ageing and ageassociated metabolic and functional decline important health challenges as they represent risk factors for various health problems, including metabolic disorders and obesity. Geriatrics aims to develop the best medical approaches to face such challenges Within this context, exercise is the best anti-ageing approach as it minimizes several age-related changes [2,3] and has been prescribed for the older population [4,5,6]. Elucidating the molecular pathways of both ageing and exercise and their mechanistic links would significantly contribute to optimizing both the available studying methods (animal models of ageing, cell cultures, etc.) and the available therapeutic tools
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