Mitochondrial Metabolism and Aging in Yeast.

Mitochondrial functionality is one of the main factors involved in cell survival, and mitochondrial dysfunctions have been identified as an aging hallmark. In particular, the insurgence of mitochondrial dysfunctions is tightly connected to mitochondrial metabolism. During aging, both mitochondrial oxidative and biosynthetic metabolisms are progressively altered, with the development of malfunctions, in turn affecting mitochondrial functionality. In this context, the relation between mitochondrial pathways and aging is evolutionarily conserved from single-celled organisms, such as yeasts, to complex multicellular organisms, such as humans. Useful information has been provided by the yeast Saccharomyces cerevisiae, which is being increasingly acknowledged as a valuable model system to uncover mechanisms underlying cellular longevity in humans. On this basis, we review the impact of specific aspects of mitochondrial metabolism on aging supported by the contributions brought by numerous studies performed employing yeast. Initially, we will focus on the tricarboxylic acid cycle and oxidative phosphorylation, describing how their modulation has consequences on cellular longevity. Afterward, we will report information regarding the importance of nicotinamide adenine dinucleotide (NAD) metabolism during aging, highlighting its relation with mitochondrial functionality. The comprehension of these key points regarding mitochondrial metabolism and their physiological importance is an essential first step for the development of therapeutic interventions that point to increase life quality during aging, therefore promoting "healthy aging," as well as lifespan itself.