Short-term caloric restriction, resveratrol, or combined treatment regimens initiated in late-life alter mitochondrial protein expression profiles in a fiber-type specific manner in aged animals

AbstractAging is associated with a loss in muscle known as sarcopenia that is partially attributed to apoptosis. In aging rodents, caloric restriction (CR) increases health and longevity by improving mitochondrial function and the polyphenol resveratrol (RSV) has been reported to have similar benefits. In the present study, we investigated the potential efficacy of using short-term (6weeks) CR (20%), RSV (50mg/kg/day), or combined CR+RSV (20% CR and 50mg/kg/day RSV), initiated at late-life (27months) to protect muscle against sarcopenia by altering mitochondrial function, biogenesis, content, and apoptotic signaling in both glycolytic white and oxidative red gastrocnemius muscle (WG and RG, respectively) of male Fischer 344×Brown Norway rats. CR but not RSV attenuated the age-associated loss of muscle mass in both mixed gastrocnemius and soleus muscle, while combined treatment (CR+RSV) paradigms showed a protective effect in the soleus and plantaris muscle (P<0.05). Sirt1 protein content was increased by 2.6-fold (P<0.05) in WG but not RG muscle with RSV treatment, while CR or CR+RSV had no effect. PGC-1α levels were higher (2-fold) in the WG from CR-treated animals (P<0.05) when compared to ad-libitum (AL) animals but no differences were observed in the RG with any treatment. Levels of the anti-apoptotic protein Bcl-2 were significantly higher (1.6-fold) in the WG muscle of RSV and CR+RSV groups compared to AL (P<0.05) but tended to occur coincident with elevations in the pro-apoptotic protein Bax so that the apoptotic susceptibility as indicated by the Bax to Bcl-2 ratio was unchanged. There were no alterations in DNA fragmentation with any treatment in muscle from older animals. Additionally, mitochondrial respiration measured in permeabilized muscle fibers was unchanged in any treatment group and this paralleled the lack of change in cytochrome c oxidase (COX) activity. These data suggest that short-term moderate CR, RSV, or CR+RSV tended to modestly alter key mitochondrial regulatory and apoptotic signaling pathways in glycolytic muscle and this might contribute to the moderate protective effects against aging-induced muscle loss observed in this study

Modeling mitochondrial dysfunctions in the brain: from mice to men

The biologist Lewis Thomas once wrote: “my mitochondria comprise a very large proportion of me. I cannot do the calculation, but I suppose there is almost as much of them in sheer dry bulk as there is the rest of me”. As humans, or indeed as any mammal, bird, or insect, we contain a specific molecular makeup that is driven by vast numbers of these miniscule powerhouses residing in most of our cells (mature red blood cells notwithstanding), quietly replicating, living independent lives and containing their own DNA. Everything we do, from running a marathon to breathing, is driven by these small batteries, and yet there is evidence that these molecular energy sources were originally bacteria, possibly parasitic, incorporated into our cells through symbiosis. Dysfunctions in these organelles can lead to debilitating, and sometimes fatal, diseases of almost all the bodies’ major organs. Mitochondrial dysfunction has been implicated in a wide variety of human disorders either as a primary cause or as a secondary consequence. To better understand the role of mitochondrial dysfunction in human disease, a multitude of pharmacologically induced and genetically manipulated animal models have been developed showing to a greater or lesser extent the clinical symptoms observed in patients with known and unknown causes of the disease. This review will focus on diseases of the brain and spinal cord in which mitochondrial dysfunction has been proven or is suspected and on animal models that are currently used to study the etiology, pathogenesis and treatment of these diseases

Apoptosis in heart and skeletal muscle

Synthèse : présentation des mécanismes fondamentaux de l'apoptose (mort cellulaire programmée), et observations s'appliquant aux tissus cardiaque et musculaire