Some Metabolites Act as Second Messengers in Yeast Chronological Aging

Abstract

The concentrations of some key metabolic intermediates play essential roles in regulating the longevity of the chronologically aging yeast Saccharomyces cerevisiae. These key metabolites are detected by certain ligand-specific protein sensors that respond to concentration changes of the key metabolites by altering the efficiencies of longevity-defining cellular processes. The concentrations of the key metabolites that affect yeast chronological aging are controlled spatially and temporally. Here, we analyze mechanisms through which the spatiotemporal dynamics of changes in the concentrations of the key metabolites influence yeast chronological lifespan. Our analysis indicates that a distinct set of metabolites can act as second messengers that define the pace of yeast chronological aging. Molecules that can operate both as intermediates of yeast metabolism and as second messengers of yeast chronological aging include reduced nicotinamide adenine dinucleotide phosphate (NADPH), glycerol, trehalose, hydrogen peroxide, amino acids, sphingolipids, spermidine, hydrogen sulfide, acetic acid, ethanol, free fatty acids, and diacylglycerol. We discuss several properties that these second messengers of yeast chronological aging have in common with second messengers of signal transduction. We outline how these second messengers of yeast chronological aging elicit changes in cell functionality and viability in response to changes in the nutrient, energy, stress, and proliferation status of the cell.

Keywords: cell signaling; chronological aging; interorganellar communications; mechanisms of longevity regulation; metabolism; mitochondria; proteostasis; regulated cell death; second messengers; yeast.

Figure 1

Mechanisms through which the concentrations of some key metabolites define the rate of chronological aging in the yeast Saccharomyces cerevisiae. These key metabolites include NADPH (A), glycerol (B), trehalose (C), H₂O₂ (D), the amino acids aspartate, asparagine, glutamate and glutamine (E), methionine (F), sphingolipids (G), spermidine (H), H₂S (I), acetic acid (J), ethanol (K), as well as FFA and DAG (L). These key metabolites are detected by a distinct set of ligand-specific protein sensors that respond to the concentration changes of the metabolites by altering the rates and efficiencies of longevity-defining cellular processes, thus creating a pro- or anti-aging cellular pattern and affecting the pace of yeast chronological aging. See text for more details. Activation arrows and inhibition bars denote pro-aging processes (displayed in blue color) or anti-aging processes (displayed in red color). Pro-aging or anti-aging metabolites are displayed in blue color or red color, respectively. Abbreviations: Asp, aspartate; Asn, asparagine; ATG, autophagy-related genes; ETC, electron transport chain; FFA, free (non-esterified) fatty acids; DAG, diacylglycerol; Glu, glutamate; Gln, glutamine; PKA, protein kinase A; RCD, regulated cell death; ROS, reactive oxygen species.