Dietary and Pharmacological Modulation of Aging-Related Metabolic Pathways: Molecular Insights, Clinical Evidence, and a Translational Model.
Level 5 - mechanism / opinion, no new human data
Narrative integrative review and conceptual translational model proposal without systematic review methodology or new human data
PubMed 41096907 · doi:10.3390/ijms26199643
What was done
Authors conducted an integrative critical review synthesizing molecular mechanisms, clinical evidence, and translational limitations of caloric restriction (CR), intermittent fasting (IF), and CR mimetics (including metformin, resveratrol, rapamycin, and spermidine). Based on these findings, they formulated a conceptual translational framework named the Active Management of Aging and Longevity (AMAL) model.
What was found
The abstract reports no quantitative values. Qualitatively, CR and IF activate AMPK and sirtuins, downregulate mTOR signaling, and enhance autophagy. In human studies, these interventions associate with improvements in insulin sensitivity, lipid profiles, low-grade inflammation, and selected epigenetic aging biomarkers. CR mimetics partially replicate these mechanistic effects, though their long-term safety and efficacy in healthy humans remain undetermined.
Why it matters
This review outlines the shared biological pathways linking dietary restriction to pharmacological mimetics and proposes a biomarker-driven framework (AMAL) to guide personalized longevity interventions.
Limits
The review relies on existing literature characterized by short trial durations, small and selective samples, intermediate surrogates rather than hard clinical endpoints (mortality, frailty, disability), and poor adherence tracking. The abstract provides no primary data, quantitative effect estimates, or systematic search methodology.
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