This 2022 paper studied caloric restriction in humans followed up by rodent experiments:
“Extension of lifespan driven by 40% caloric restriction (CR) in rodents causes trade-offs in growth, reproduction, and immune defense that make it difficult to identify therapeutically relevant CR-mimetic targets. We report that about 14% CR for 2 years in healthy humans improved thymopoiesis.
Expression of the gene PLA2G7 is inhibited in humans undergoing CR. Deletion of Pla2g7 in mice showed decreased thymic lipoatrophy, protection against age-related inflammation, lowered NLRP3 inflammasome activation, and improved metabolic health.
Twenty-four-month-old PLA2G7-deficient mice (analogous to ~70-year-old humans) had larger thymi and higher thymocyte abundance, and were protected from age-related thymic involution.
We propose that reduction of PLA2G7 caused by CR in humans might contribute to better adipose tissue metabolism, lower inflammation, and reduced thymic lipoatrophy.”
https://www.science.org/doi/10.1126/science.abg7292 “Caloric restriction in humans reveals immunometabolic regulators of health span” (not freely available). Thanks to Dr. Alexander Predeus for providing a copy.
I would have liked rodent experiments to continue another year or so to determine the control group’s and PLA2G7-deficient group’s healthspans and lifespans. These researchers could have strengthened their findings if increased healthspans also increased lifespans.