Caloric restriction in humans reveals immunometabolic regulators of health span.
Level 3 - non-randomized controlled study
Prospective human interventional cohort study combined with preclinical mouse models (randomization not specified in abstract)
PubMed 35143297 · doi:10.1126/science.abg7292
What was done
Healthy humans underwent approximately 14% caloric restriction (CR) for 2 years to assess effects on thymopoiesis, intrathymic ectopic lipid mobilization, and adipose tissue transcriptional reprogramming. Gene expression changes in humans led to experiments in Pla2g7-knockout mice to test the role of platelet-activating factor acetylhydrolase in thymic lipoatrophy, NLRP3 inflammasome activation, age-related inflammation, and metabolic health.
What was found
About 14% CR over 2 years in humans improved thymopoiesis, mobilized intrathymic ectopic lipid, induced transcriptional pathways for mitochondrial bioenergetics and anti-inflammatory responses, and inhibited Pla2g7 expression. In mice, Pla2g7 deletion reduced thymic lipoatrophy, decreased NLRP3 inflammasome activation, protected against age-related inflammation, and improved metabolic health. No exact numerical effect sizes, dispersion metrics, or p-values are reported in the abstract.
Why it matters
It identifies PLA2G7 as an immunometabolic mediator influenced by moderate caloric restriction in humans, offering a potential therapeutic target to reduce inflammation and extend healthspan without severe caloric restriction.
Limits
The abstract does not state the human sample size, control group details, or quantitative effect sizes. Causal manipulation of the PLA2G7 pathway was performed in mice rather than humans.
Cited by
- supports In a two-year human caloric restriction study (the CALERIE study) from Yale, caloric restriction slowed thymic aging.