The regeneration model of aging and its practical implications

Aging is a primary risk factor for multi-morbidity and declining quality of life. The geroscience hypothesis posits that targeting biological aging mechanisms may prevent or delay morbidity, yet translating theory into practice remains challenging. Unknown long-term risks and a lack of well-validated, responsive, and practical surrogate endpoints hinder the field’s preventive aspirations. This review addresses these obstacles by introducing the biological aging cycle and the closely related regeneration model of aging—frameworks that integrate biological aging processes and distill the complexity of aging into a series of fundamental steps. The model provides insights into potential trade-offs of anti-aging interventions and can guide strategies to slow aging across diverse populations. Further, the frameworks collectively highlight AMP-activated protein kinase (AMPK) and DNA damage as master regulators of aging checkpoints and promising surrogates for healthy and unhealthy aging, respectively. A series of lifestyle-based case studies are subsequently provided to support the validity of these ideas. The resulting principles could transform geroscience, nutrition, and lifestyle medicine and pave the way for innovative approaches to extend healthspan.