期刊
EXPERIMENTAL GERONTOLOGY
卷 98, 期 -, 页码 99-109出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exger.2017.08.017
关键词
Acetyl-L-carnitine; Aging brain; Mitochondrial biogenesis; PGC-1s signalling cascade; Mitochondrial dynamics
资金
- Sigma-Tau Industrie Farmaceutiche Riunite S.p.A.
- fiRSt s.r.l. Rome, Italy
- FIRB-MERIT [RBNE08HWLZ_012]
- University of Bari-Finanziamenti di Ateneo
- Fondazione Roma NCDs Call
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-1 alpha and PGC-1 beta and of the factors regulating mitochondrial biogenesis, finding an age-related decrease of PGC-1 beta, whereas PGC-1 alpha 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-1 beta. 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.
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