Resetting the aging clock through epigenetic reprogramming: Insights from natural products

Epigenetic modifications play a critical role in regulating gene expression under various physiological and pathological conditions. Epigenetic modifications reprogramming is a recognized hallmark of aging and a key component of the aging clock used to differentiate between chronological and biological age. The potential for prospective diagnosis and regulatory capabilities position epigenetic modifications as an emerging drug target to extend longevity and alleviate age-related organ dysfunctions. In the past few decades, numerous preclinical studies have demonstrated the therapeutic potential of natural products in various human diseases, including aging, with some advancing to clinical trials and clinical application. This review highlights the discovery and recent advancements in the aging clock, as well as the potential use of natural products as anti-aging therapeutics by correcting disordered epigenetic reprogramming. Specifically, the focus is on the imbalance of histone modifications, alterations in DNA methylation patterns, disrupted ATP-dependent chromatin remodeling, and changes in RNA modifications. By exploring these areas, new insights can be gained into aging prediction and anti-aging interventions.