Advances in Understanding of the Role of Lipid Metabolism in Aging

Abstract

During aging, body adiposity increases with changes in the metabolism of lipids and their metabolite levels. Considering lipid metabolism, excess adiposity with increased lipotoxicity leads to various age-related diseases, including cardiovascular disease, cancer, arthritis, type 2 diabetes, and Alzheimer's disease. However, the multifaceted nature and complexities of lipid metabolism make it difficult to delineate its exact mechanism and role during aging. With advances in genetic engineering techniques, recent studies have demonstrated that changes in lipid metabolism are associated with aging and age-related diseases. Lipid accumulation and impaired fatty acid utilization in organs are associated with pathophysiological phenotypes of aging. Changes in adipokine levels contribute to aging by modulating changes in systemic metabolism and inflammation. Advances in lipidomic techniques have identified changes in lipid profiles that are associated with aging. Although it remains unclear how lipid metabolism is regulated during aging, or how lipid metabolites impact aging, evidence suggests a dynamic role for lipid metabolism and its metabolites as active participants of signaling pathways and regulators of gene expression. This review describes recent advances in our understanding of lipid metabolism in aging, including established findings and recent approaches.

Keywords: age-related diseases; aging; lipid metabolism.

Figure 1

Age-related changes in lipid metabolism and their effects on aging and age-related diseases. Ectopic lipid accumulation occurring during aging is mainly induced by increased fatty acids uptake, de novo lipogenesis, with decreased fatty acid oxidation process. Mitochondrial integrity and autophagic induction is also diminished during aging leading to decreased lipid catabolism. These changes further bring lipotoxicity in the cell, deplete energy in the tissue, and alter cellular signaling causing accelerated aging and early onset of age-related diseases.

Figure 2

Changes in adipose tissue during aging and their effects to systemic aging. Compared to young adipose tissue, aged adipose tissue has enlarged, senescent adipocyte phenotype causing changes in adipokine secretion. Increase in inflammatory cells in adipose tissue secretes cytokines and chemokines that can circulate throughout the body. These changes during aging causes systemic inflammation and metabolic disorders.