Year: 2026
Type: article
Abstract: <?A3B2 tlsb=.01w?>With the acceleration of global population aging, the rising prevalence of age-related diseases presents unprecedented challenges to individual health, public health systems, and sustainable economic development. Long-lived individuals serve as ideal natural models for researching healthy aging, since they have successfully delayed or even avoided the onset of major age-related diseases. This unique longevity phenotype is not attributed to a single factor but reflects the cumulative protective contributions of multidimensional factors, including genetic endowment, epigenetic modifications, and environmental lifestyles. This article provides a comprehensive review of recent advances in understanding the mechanisms of healthy aging derived from longevity cohort studies. Firstly, we explore the foundational role of the genetic blueprint in maintaining systemic homeostasis. We discuss how important longevity loci, such as FOXO3A, APOE and IL-6, defend against molecular damage by reshaping energy networks, optimizing lipid metabolic profiles, and building immune resilience, while also exploring the roles of genetic buffering and environmental selection in sex differences in longevity. Then, we review current findings regarding gene expression regulation in healthy aging, noting that long-lived individuals exhibit younger DNA methylation landscapes and utilize non-coding RNA networks for transcriptional regulation, and mention the association between enhanced proteostasis and longevity. Finally, we discuss the exogenous influences of environment-organism interactions on the maintenance of healthy aging. We specifically focus on the role of the gut microbiota in supporting metabolism and immunity within longevity cohorts, as well as its causal relationship with longevity, while also summarizing the combined benefits of lifestyle interventions, such as caloric restriction, physical exercise, and psychological resilience. Deeply understanding these multidimensional protective mechanisms is the key to decoding the mysteries of human longevity and provides a theoretical basis for developing novel <?A3B2 tlsb=.03w?>anti-aging strategies. Future translational research based on these mechanisms is expected to drive the transition from <?A3B2 tlsb?> ″longevity molecule discovery″ to ″longevity medical interventions″, ultimately extending human healthspan and facilitating a transition toward a high-quality healthy aging society.
Source: Shengming kexue
DOI: 10.3724/cbls.2026108
Authors: Fan-Qian YIN, Qing-Peng KONG
Institutions: Kunming Institute of Zoology, Chinese Academy of Sciences
Language: English
Subfield: Aging
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W7167833994