One-Carbon Metabolism: Pulling the Strings behind Aging and Neurodegeneration

Abstract

One-carbon metabolism (OCM) is a network of biochemical reactions delivering one-carbon units to various biosynthetic pathways. The folate cycle and methionine cycle are the two key modules of this network that regulate purine and thymidine synthesis, amino acid homeostasis, and epigenetic mechanisms. Intersection with the transsulfuration pathway supports glutathione production and regulation of the cellular redox state. Dietary intake of micronutrients, such as folates and amino acids, directly contributes to OCM, thereby adapting the cellular metabolic state to environmental inputs. The contribution of OCM to cellular proliferation during development and in adult proliferative tissues is well established. Nevertheless, accumulating evidence reveals the pivotal role of OCM in cellular homeostasis of non-proliferative tissues and in coordination of signaling cascades that regulate energy homeostasis and longevity. In this review, we summarize the current knowledge on OCM and related pathways and discuss how this metabolic network may impact longevity and neurodegeneration across species.

Keywords: Alzheimer’s disease; Parkinson disease; aging; diet; folate; metabolism; methionine; mitochondria; neurodegeneration; one-carbon vitamins.

Figure 1

One−carbon metabolic pathways. Intersections of OCM pathways in cytosolic, nuclear, and mitochondrial compartments, based on mammalian systems. The involved folate forms are depicted in green boxes, while the respective enzymes are written in red.