Insights on the role of L-lactate as a signaling molecule in skin aging

Abstract

L-lactate is a catabolite from the anaerobic metabolism of glucose, which plays a paramount role as a signaling molecule in various steps of the cell survival. Its activity, as a master tuner of many mechanisms underlying the aging process, for example in the skin, is still presumptive, however its crucial position in the complex cross-talk between mitochondria and the process of cell survival, should suggest that L-lactate may be not a simple waste product but a fine regulator of the aging/survival machinery, probably via mito-hormesis. Actually, emerging evidence is highlighting that ROS are crucial in the signaling of skin health, including mechanisms underlying wound repair, renewal and aging. The ROS, including superoxide anion, hydrogen peroxide, and nitric oxide, play both beneficial and detrimental roles depending upon their levels and cellular microenvironment. Physiological ROS levels are essential for cutaneous health and the wound repair process. Aberrant redox signaling activity drives chronic skin disease in elderly. On the contrary, impaired redox modulation, due to enhanced ROS generation and/or reduced levels of antioxidant defense, suppresses wound healing via promoting lymphatic/vascular endothelial cell apoptosis and death. This review tries to elucidate this issue.

Keywords: Aging; L-lactate; Mito-hormesis; Redox signaling; Skin.

Fig. 1

A schematic representation of l-lactate activity within the pathogenesis of premature/extrinsic skin aging. In the center of the cartoon is simplified the complex balance on ROS production by mitochondria, in order to assess ROS as signaling molecules. This mechanism allows mitochondria biogenesis, uncoupled events, mitokinesis and mitochondria fission/fusion, via the PGC-1α but l-lactate is also able to use oxidized lipids to trigger the Nrf2/keap1/ARE via mitohormetic mechanism. The activity by l-lactate on HIF-1α allows to bring together two quite opposite but interplaying pathways, i.e. the Nrf2/Keap1/ARE pathway with HO-1 and the MAPK/NF-κB pathway. Aging in the skin is exemplified by events within squares red lined squares, whereas events reverting the aging process and promoting survival and renewal are green lined squares. l-lactate is indicated as “l” within a green circle (if promoting or triggering), pale yellow if regulating, red if inhibiting. DAMP damage associated molecular pattern, HO-1 heme oxygenase-1, NF-kB nuclear factor kappa‐B, NLR family pyrin domain containing 3, PAMP pathogen associated molecular pattern