A combination of lithium and glycyrrhizic acid has anti-aging effects via increase of intracellular pH. Hypothesis of cytosol acidification as one of the driving forces of aging.

Optimal intracellular pH (pHi) provides a necessary environment for the activity of key biochemical processes, including glycolysis, mitochondrial function, and genomic function; it also affects membrane potential, cell growth, and polymerization of the cytoskeleton. The aging process is accompanied by gradual acidification of pHi, affecting these and numerous other intercellular processes. In this study, we investigate the potential role of a combined treatment of lithium and glycyrrhizic acid (CRX) to counteract pHi acidification. We observe concomitant reversal of many of the generally accepted physiological attributes of the aging process. In cell culture, treatment with the combination of lithium and glycyrrhizic acid caused decreased expression of the senescence marker beta-galactosidase, as well as altered expression of other genes associated with aging and enhanced mitochondrial respiration. Our results provide preliminary data supporting the hypothesis that increasing pHi may reverse some of the markers of age-related physiological processes.