Beyond dietary restriction: Towards next-generation precision diets for healthy aging

Longevity is governed by complex interactions between genes and environment, in which diet is among the most powerful modifiable determinants. Although classical dietary restriction reliably extends lifespan, evidence from more than thirty large prospective cohorts and meta-analyses summarized in this review indicates that meaningful longevity benefits can be achieved without caloric restriction by optimizing macronutrient composition. This precision-nutrition strategy targets carbohydrate quality, protein sources and specific amino acids, lipid class, and dietary fiber, and adapts these choices to age, sex, genetic background, metabolic phenotype, and gut microbiome composition. This review integrates findings from model organisms, mechanistic investigations, and large-scale prospective cohorts to describe how macronutrients and their combinations modulate lifespan-associated nutrient-sensing pathways. An age-stratified macronutrient framework and a longevity dietary pyramid are proposed, both of which address how nutritional recommendations should evolve from young adulthood through old age. The framework is further situated within a broader precision-nutrition paradigm that incorporates continuous glucose monitoring, multi-omics profiling, microbiome-guided personalization, time-restricted eating, and emerging digital tools such as wearable monitoring and artificial-intelligence-assisted diet design. Together, these elements bridge mechanistic insight and population-level evidence, and provide a foundation for precision diets aimed at extending healthspan and promoting healthy longevity.