Repeated Cycles of a Fasting-Mimicking Diet Reduce Measures of Biological Age

Development of the fasting-mimicking diet resulted from efforts to find out where the beneficial response to fasting begins; how much can one eat and still be effectively fasting? Where is the trigger point? An individual can in fact gain a majority of the benefits of fasting at around 600 calories per day, and five days of fasting mimicking produces beneficial changes in metabolism that can last for months. A formal fasting mimicking diet was created has undergone clinical trials as an adjuvant therapy in the treatment of cancer. In practice fasting mimicking is easily carried out at home without the formal diet: count calories, eat sensibly. Here, researchers show that Klemera-Doubal biological age is lowered by a few years following fasting mimicking, alongside a measure of immune system aging, an interesting result.

In mice, periodic cycles of a fasting mimicking diet (FMD) protect normal cells while killing damaged cells including cancer and autoimmune cells, reduce inflammation, promote multi-system regeneration, and extend longevity. Here, we test the hypothesis that FMD cycles improve the levels of multiple markers of aging thus reducing biological age as measured by a set of validated blood markers and by other cellular and metabolic measurements. We report on the secondary outcome measures of the FMD-trial (NCT02158897) which are biomarkers associated with aging or age-related diseases, and metabolic syndrome, including visceral and hepatic fat, lymphoid/myeloid ratios, and blood markers, which were not investigated in the original report.

We show that 3 FMD cycles in adult study participants are associated with reduced insulin resistance and other pre-diabetes markers, lower hepatic fat (as determined by magnetic resonance imaging), and increased lymphoid to myeloid ratio, an indicator of immune system age. Based on the Klemera-Doubal measure of biological age predictive of morbidity and mortality, 3 FMD cycles were associated with a decrease of 2.5 years in median biological age, independent of weight loss. Nearly identical findings resulted from a second clinical study (NCT04150159). Together these results provide initial support for beneficial effects of the FMD on multiple cardiometabolic risk factors and biomarkers of biological age.

Link: https://doi.org/10.1038/s41467-024-45260-9