Phenotype consequences of myophosphorylase dysfunction: insights from the McArdle mouse model

McArdle disease, caused by inherited deficiency of the enzyme muscle glycogen phosphorylase (GP-MM), is arguably the paradigm of exercise intolerance. The recent knock-in (p.R50X/p.R50X) mouse disease model allows an investigation of the phenotypic consequences of muscle glycogen unavailability and the physiopathology of exercise intolerance. We analysed, in 2-month-old mice [wild-type (wt/wt), heterozygous (p.R50X/wt) and p.R50X/p.R50X)], maximal endurance exercise capacity and the molecular consequences of an absence of GP-MM in the main glycogen metabolism regulatory enzymes: glycogen synthase, glycogen branching enzyme and glycogen debranching enzyme, as well as glycogen content in slow-twitch (soleus), intermediate (gastrocnemius) and glycolytic/fast-twitch (extensor digitorum longus; EDL) muscles.

'Adipaging': Aging and obesity share biological hallmarks related to a dysfunctional adipose tissue

The increasing aging of our societies is accompanied by a pandemic of obesity and related cardiometabolic disorders. Progressive dysfunction of the white adipose tissue is increasingly recognized as an important hallmark of the aging process which in turn contributes to metabolic alterations, multi-organ damage, and a systemic pro-inflammatory state ('inflammaging'). On the other hand, obesity, the paradigm of adipose tissue dysfunction, shares numerous biological similarities with the normal aging process such as chronic inflammation and multi-system alterations. Accordingly, understanding the interplay between accelerated aging related to obesity and adipose tissue dysfunction is critical to gain insight into the aging process in general as well as into the pathophysiology of obesity and other related conditions. Here we postulate the concept of 'adipaging' to illustrate the common links between aging and obesity and the fact that, to a great extent, obese adults are prematurely aged individuals.