<p>Aging is a primary risk factor for multi-morbidity and declining quality of life. The geroscience hypothesis states that targeting biological aging mechanisms may prevent or delay morbidity; however, translating theory into practice remains challenging. Unknown long-term risks and a lack of well-validated, responsive, and practical surrogate endpoints especially hinder the field’s preventive aspirations. This review addresses these obstacles by introducing the regeneration model of aging—a novel framework that integrates biological aging processes and distills 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 framework highlights AMP-activated protein kinase (AMPK) as a master regulator of anti-aging checkpoints and a promising surrogate endpoint for healthy aging. A series of lifestyle-based case studies is 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 achieve healthy old age and longevity.</p>