Caloric restriction (CR) is one of only two interventions — alongside rapamycin — that has ever extended lifespan across all four model-organism categories tested by the Interventions Testing Program (ITP) (yeast, worms, flies, mammals).
The sirtuin hypothesis was falsified. CR's longevity effect was long believed to work through the sirtuin pathway. This was falsified across multiple yeast strains: some strains respond to CR but not sirtuin overexpression, others show the reverse, and a 2004 study (Kaplan & Kennedy) found the two effects were independent and additive, not synergistic — 'there's no evidence whatsoever that sirtuins have anything to do with caloric restriction and vice versa.' Only one transgenic mouse model (SIRT6 overexpression) has shown a survival benefit, and only in males (10–15% longer life); females showed no extension.
Resveratrol, marketed on the sirtuin/CR-mimetic story (the 'French Paradox'), showed categorically nothing in ITP testing — achieving the doses studied would require drinking one's body weight in wine daily.
This falsification matters for NAD Precursor Supplementation (NR, NMN, IV NAD): NAD is consumed as a substrate by sirtuins during DNA repair, and the (now-discredited) sirtuin/CR link was part of the rationale for believing NAD-boosting supplements would replicate CR's benefits. See Longevity Intervention Classification Frameworks for how CR fits Attia's 'essential behavioral' category alongside eating, sleeping, and moving.
Из тем: Longevity Interventions