Search

Motor neuron degeneration, denervation, neuromuscular junction (NMJ) fragmentation and loss of motor units (MUs), play a key-role in the development of sarcopenia. The aim of the present study was to investigate the beneficial effects of regular practice of dancing in physically active elders on concentration of C-terminal Agrin fragment (CAF), a marker of NMJ instability, muscle mass, strength, and physical performance in a group of 16 recreationally active older dancers (AOD; 70.1 ± 3.4 yr) compared to 15 age-matched sedentary peers (OS; 70.9 ± 6.2 yr). Circulating concentration of CAF was measured in serum, while morphology of the vastus lateralis and multifidus muscles was assessed by ultrasound imaging. In addition, the participants underwent two functional performance tests, the Timed Up and Go (TUG) and the 10-meter walk test (10-MWT), a lower and upper limb isometric strength test, a static and a dynamic balance test. Although no statistically significant differences were detected for both muscle morphology and isometric strength, higher CAF concentration (20%, p < 0.01) was found in OS. AOD showed a better performance in TUG (22%, p < 0.001), 10-MWT (17%, p < 0.001) and dynamic balance (25%, p < 0.01) than OS. Notably, CAF concentration correlated with dynamic balance performance (r = 0.3711, p < 0.05). Our results provide evidence that the regular practice of dancing in older age, together with non-structured light aerobic physical activities, is associated to lower CAF concentration and improved walking and balance performance. Our findings also suggest that NMJ instability, as indicated by elevated CAF serum concentration, seems to precede the loss of muscle size and alterations in muscle architecture normally associated with sarcopenia., (Copyright © 2021 Elsevier Inc. All rights reserved.)

We previously reported the ability of dietary supplementation with acetyl-l-carnitine (ALCAR) to prevent age-related decreases of mitochondrial biogenesis in skeletal muscle and liver of old rats. Here, we investigate the effects of ALCAR supplementation in cerebral hemispheres and cerebellum of old rats by analyzing several parameters linked to mitochondrial biogenesis, mitochondrial dynamics and antioxidant defenses. We measured the level of the coactivators PGC-1α and PGC-1β and of the factors regulating mitochondrial biogenesis, finding an age-related decrease of PGC-1β, whereas PGC-1α level was unvaried. Twenty eight-month old rats supplemented with ALCAR for one and two months showed increased levels of both factors. Accordingly, the expression of the two transcription factors NRF-1 and TFAM followed the same trend of PGC-1β. The level of mtDNA, ND1 and the activity of citrate synthase, were decreased with aging and increased following ALCAR treatment. Furthermore, ALCAR counteracted the age-related increase of deleted mtDNA. We also analyzed the content of proteins involved in mitochondrial dynamics (Drp1, Fis1, OPA1 and MNF2) and found an age-dependent increase of MFN2 and of the long form of OPA1. ALCAR treatment restored the content of the two proteins to the level of the young rats. No changes with aging and ALCAR were observed for Drp1 and Fis1. ALCAR reduced total cellular levels of oxidized PRXs and counteracted the age-related decrease of PRX3 and SOD2. Overall, our findings indicate a systemic positive effect of ALCAR dietary treatment and a tissue specific regulation of mitochondrial homeostasis in brain of old rats. Moreover, it appears that ALCAR acts as a nutrient since in most cases its effects were almost completely abolished one month after treatment suspension. Dietary supplementation of old rats with this compound seems a valuable approach to prevent age-related mitochondrial dysfunction and might ultimately represent a strategy to delay age-associated negative consequences in mitochondrial homeostasis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Extremely interesting for aging research are those individuals able to reach older ages still with functions similar to those of younger counterparts. We examined liver samples from ad libitum-fed old (28-month-old, AL-28) and ad libitum-fed very old (32-month-old, AL-32) rats for a number of markers, relevant for mitochondrial functionality and mitochondrial DNA (mtDNA) content. As for the mtDNA content and the protein amounts of the citrate synthase and the antioxidant peroxiredoxin III there were no significant changes in the AL-32 animals. No significant longevity-related change was found for TFAM amount, but a 50% reduction in the amount of the Lon protease, responsible for turnover of TFAM inside mitochondria, characterized the AL-32 rats. No longevity-related change was observed also for the amounts of the mtDNA repair enzymes OGG1 and APE1, whereas the intra-mitochondrial amount of the cytochrome c protein showed a 50% increase in the AL-32 rats, indicating a likely reduced initiation of the intrinsic apoptotic pathway. Totally unexpected was the doubling of two proteins, very relevant for mitochondrial dynamics, namely MFN2 and DRP1, in the AL-32 rats. This prompted us to the calculation of all individual fusion indexes that grouped together in the AL-32 rats, while in the AL-28 animals were very different. We found a strong positive correlation between the fusion indexes and the respective mtDNA contents in two AL-28 and four AL-32 rats. This supports the idea that the limited prevalence of fusion above a still active fission should have ensured a functional mitochondrial network and should have led to a quite narrow range of high mtDNA contents, likely the best-suitable for extended longevity. Our findings strongly suggest that, among the multiple causes leading to the longevity of the AL-32 rats, the maintenance of an adult-like balance of mitochondrial dynamics seems to be very relevant for the regulation of mtDNA content and functionality., (Copyright © 2016 Elsevier Inc. All rights reserved.)