Green · Nature reviews. Molecular cell biology 2022 · narrative review · n=?

Molecular mechanisms of dietary restriction promoting health and longevity.

Cited 749 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review discussing animal models and molecular pathways without systematic search or new human empirical data.

PubMed 34518687 · doi:10.1038/s41580-021-00411-4 · record verified 2026-08-27

What was done

This narrative review synthesizes literature on dietary restriction, fasting protocols, protein restriction, and essential amino acid reductions (methionine and branched-chain amino acids) in mammalian models (rodents and non-human primates) and humans, detailing their effects on nutrient-sensing signaling pathways including AKT, FOXO, mTOR, NAD+, AMPK, and FGF21.

What was found

The abstract reports no quantitative values or effect estimates. It qualitatively describes that dietary restriction delays aging, extends healthspan and lifespan in mammalian models, induces metabolic changes associated with human disease prevention, and selectively alters key geroprotective signaling cascades.

Why it matters

It outlines a comprehensive molecular framework connecting specific dietary manipulations to conserved signaling networks that regulate mammalian aging.

Limits

As a narrative review, it lacks systematic search methodology, pooled quantitative outcomes, or new primary experimental data. Much of the underlying mechanistic evidence derives from non-human model organisms rather than clinical human trials.

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