Emerging Insights into the Metabolic Alterations in Aging Using Metabolomics

Abstract

Metabolomics is the latest 'omics' technology and systems biology science that allows for comprehensive profiling of small-molecule metabolites in biological systems at a specific time and condition. Metabolites are cellular intermediate products of metabolic reactions, which reflect the ultimate response to genomic, transcriptomic, proteomic, or environmental changes in a biological system. Aging is a complex biological process that is characterized by a gradual and progressive decline in molecular, cellular, tissue, organ, and organismal functions, and it is influenced by a combination of genetic, environmental, diet, and lifestyle factors. The precise biological mechanisms of aging remain unknown. Metabolomics has emerged as a powerful tool to characterize the organism phenotypes, identify altered metabolites, pathways, novel biomarkers in aging and disease, and offers wide clinical applications. Here, I will provide a comprehensive overview of our current knowledge on metabolomics led studies in aging with particular emphasis on studies leading to biomarker discovery. Based on the data obtained from model organisms and humans, it is evident that metabolites associated with amino acids, lipids, carbohydrate, and redox metabolism may serve as biomarkers of aging and/or longevity. Current challenges and key questions that should be addressed in the future to advance our understanding of the biological mechanisms of aging are discussed.

Keywords: MS; NMR; aging; biomarker; human longitudinal studies; metabolism; metabolites; metabolomics; model organisms.

Figure 1

Systems biology approaches in aging research. Aging is associated with changes at the molecular, cellular, tissue, and organismal levels. The systems biology ‘omics’ technologies i.e., genomics, transcriptomics, proteomics, and metabolomics enable high-throughput quantitative profiling of molecules in biological systems to reveal global changes that are associated with aging. Integration of the multi-layered omics data is highly critical for a complete understanding of the biological mechanisms of aging. Notably, unlike the DNA, mRNA, and proteins, the metabolites are not directly involved in the “central dogma” of information flow.

Figure 2

Metabolism integrates the effects of diet, environment, and genetics in aging. Aging is influenced by the alterations in genetics or epigenetics, diet and lifestyle factors, and environmental exposure. The phenotype of an organism is resultant of the interactions of the genotype with diet, lifestyle, and environmental factors. Metabolites represent the final fingerprint or snapshot of all molecular changes associated with a phenotype. Metabolic profiles thus integrate the effects of genetics, diet, and environment in aging.