Role of AMPK and Sirtuins in Aging Heart: Basic and Translational Aspects

Abstract

Aging is a key risk factor for numerous diseases, including cardiac diseases. High energy demands of the heart require precise cellular energy sensing to prevent metabolic stress. AMPK and sirtuins are key intracellular metabolic sensors regulating numerous cell functions, like mitochondrial function and biogenesis, autophagy, and redox balance. However, their function is impaired during the aging process leading to mitochondrial dysfunction, oxidative stress, and inflammation culminating in cardiovascular diseases. The underlying molecular mechanisms leading to dysfunction of metabolic sensing in the aging heart are complex and comprise both intracellular and systemic age-related alterations. In this study, we overview the current knowledge on the impact of aging on cardiac metabolic sensing, with a focus on AMPK and sirtuins, while mTOR pathway was only marginally considered. A particular focus was given to systemic factors, e.g., inflammation, vascular diseases, and microbiome.

Figure 1.

Schematic presentation of the role of AMPK and sirtuins in cardiac aging. Aging and the associated low-grade systemic inflammation lead to the reduced activity of cardiac AMPK and sirtuins. This causes a disturbance of mitochondrial and redox homeostasis, accompanied by a reduced autophagy and activation of inflammasomes. Overall, these events promote cardiac inflammation and senescence leading to the release of proinflammatory cytokines and further amplification of systemic inflammation. Finally, cardiac inflammation leads to vascular dysfunction and heart failure.