Acetyl‐l‐carnitine protects yeast cells from apoptosis and aging and inhibits mitochondrial fission

Summary In this work we report that carnitines, in particular acetyl -L- carnitine (ALC), are able to prolong the chronologicalaging of yeast cells during the stationary phase. Lifespanextension is significantly reduced in yca1 mutants as wellin rho 0 strains, suggesting that the protective effects passthrough the Yca1 caspase and mitochondrial functions.ALC can also prevent apoptosis in pro-apoptotic mutants,pointing to the importance of mitochondrial functions inregulating yeast apoptosis and aging. We also demon-strate that ALC attenuates mitochondrial fission in agedyeast cells, indicating a correlation between its protectiveeffect and this process. Our findings suggest that ALC,used as therapeutic for stroke, myocardial infarction andneurodegenerative diseases, besides the well-knownanti-oxidant effects, might exert protective effects alsoactingonmitochondrial morphology.Key words: aging; apoptosis; carnitine; mitochondria;S. cerevisiae. Introduction Genetic studies on lifespan determination revealed a large num-ber of potential targets for chemical compounds to slow aging.Because aging is a main risk factor in human cancer or neurode-generative diseases, such compounds may prove useful inretarding age-related diseases.Reducing energy intake by controlled caloric restriction orintermittent fasting increases lifespan and protects various tis-sues against disease. Genetics has revealed that aging in severalorganisms may be controlled by changes in the intracellularNAD⁄NADH ratio regulating sirtuins, a group of proteins linkedto aging, as well by changes in metabolism and stress tolerance(Calabrese et al., 2008).It has been demonstrated that the neuroprotective effects ofdietary antioxidants, including curcumin, acetyl