Intermittent Fasting

Strong mechanistic evidence. Human trials show benefits for weight, metabolic health, and inflammatory markers. Various protocols studied (16:8, 5:2, etc.). UPDATE (August 2026): A systematic review of human nutritional interventions and cellular senescence (Ageing Research Reviews 2026; 29 articles, 27 trials, 3,811 participants) identified calorie restriction as producing the most recurrent reductions in circulating inflammatory and SASP-panel factors and in senescence-associated transcriptomic signatures - the strongest such signal of any nutritional strategy reviewed. Importantly, classical markers of senescent-cell abundance (CDKN2A/p16, CDKN1A/p21) and telomere length were largely unchanged or highly variable across the same trials. Fasting and CR therefore have the best human evidence for modulating the senescence-associated secretory environment, without established evidence of reducing senescent-cell burden itself. UPDATE (September 13, 2026): A peer-reviewed study in Cell (Grońska-Pęski, Acosta-Rodríguez et al., NYU/NIA, 9 Sep 2026) extends caloric restriction's effects to genome maintenance. Using high-fidelity duplex sequencing of bulk liver, bulk kidney, hepatocytes and cerebellar neurons, CR reduced genome-wide somatic mutation burden — both substitutions and indels — across tissues, and specifically lowered activity of SBS5, the clock-like mutational process responsible for most mammalian mutations. The reduction was largest in transcriptionally inactive regions, which argues against a simple transcription-coupled-repair explanation. This makes somatic mutation accumulation, long treated as an irreversible substrate of aging, look dose-responsive and diet-modifiable. Important boundaries: this is mouse CR, not human time-restricted eating; causality for lifespan is not demonstrated; and the finding does not transfer automatically to CR mimetics or to intermittent-fasting protocols, whose human evidence remains centred on metabolic and SASP-related markers.

Evidence Scale