Mechanisms of Aging and the Preventive Effects of Resveratrol on Age-Related Diseases

Abstract

Aging gradually decreases cellular biological functions and increases the risk of age-related diseases. Cancer, type 2 diabetes mellitus, cardiovascular disease, and neurological disorders are commonly classified as age-related diseases that can affect the lifespan and health of individuals. Aging is a complicated and sophisticated biological process involving damage to biochemical macromolecules including DNA, proteins, and cellular organelles such as mitochondria. Aging causes multiple alterations in biological processes including energy metabolism and nutrient sensing, thus reducing cell proliferation and causing cellular senescence. Among the polyphenolic phytochemicals, resveratrol is believed to reduce the negative effects of the aging process through its multiple biological activities. Resveratrol increases the lifespan of several model organisms by regulating oxidative stress, energy metabolism, nutrient sensing, and epigenetics, primarily by activating sirtuin 1. This review summarizes the most important biological mechanisms of aging, and the ability of resveratrol to prevent age-related diseases.

Keywords: age-related diseases; aging; resveratrol.

Figure 1

The structure of resveratrol.

Figure 2

The anti-cancer, anti-neurodegenerative, and anti-aging effects of resveratrol are exerted through intracellular signal transduction pathways. Inhibition of PKC by resveratrol in turn induces the inhibition of COX and LOX, which can induce the synthesis of proinflammatory molecules that are critical for the initiation of tumorigenesis. Further, the expression of the pro-apoptotic Bax gene is stimulated by p53 or other transcription factors, and downregulation of the anti-apoptotic protein Bcl-2 leads to mitochondria-mediated apoptosis. Resveratrol can also inhibit PDE, which increases the concentrations of cAMP and Ca²⁺. The increase in cAMP and Ca²⁺ promotes AMPK and Nrf2, respectively, resulting in the activation of autophagy through the inhibition of mTOR. AMPK increases cellular NAD⁺ levels, which further promotes SIRT1 activity. Resveratrol can activate SIRT1, thus inhibiting phosphorylation of the p65 subunit of NF-kB. This causes a reduction in transcription of the proinflammatory gene and inhibition of ROS and cytokine production, leading to anti-aging effects.