Cycles of a diet that mimics fasting can reduce signs of immune system aging, as well as insulin resistance and liver fat

A recent Nature Communications study performed analyses of blood samples obtained from a randomized clinical trial. It showed that three cycles of fasting-mimicking diet (FMD) in adults were associated with lower pre-diabetes markers, lower hepatic fat, and a higher lymphoid-to-myeloid ratio, which is an indicator of the aging of the immune system. 

Background

Metabolic syndromes are characterized by the co-occurrence of three symptoms from within: abdominal obesity, dyslipidemia, insulin resistance, and elevated CRP levels. Research has shown that obesity accelerates liver aging and acts on other molecular hallmarks of aging. Another feature of aging is immunosenescence, which is the altered function and composition of the immune system. 

Dysfunction in different types of cells stemming from aging is at the center of many diseases, including cancer, cardiovascular disease, and so on. This suggests that intervening in the aging process could lead to the prevention or amelioration of human diseases. This has indeed been noted in animal models where slowing down cellular deterioration led to new or functional intra-cellular components.

Everyday nutrition has been seen to play a crucial role in speeding up the aging process in rodents, and this could possibly be true in humans as well. Besides the nutrient content, the number of hours for which meals are consumed influences lifespan and health. In this regard, time-restricted eating (TRE), periodic water-only fasting (PF), and intermittent fasting (IF) have gained popularity recently. 

About the study

A fasting-mimicking diet (FMD) is a low-calorie, plant-based, and low-protein dietary intervention that lasts for 5-days. FMD followed by a normal diet has been seen to have positive effects on both cellular healthspan and function. The hypothesis tested here was that FMD cycles reduce biological age by improving the levels of various markers of aging.

For this study, blood samples were obtained from a randomized control trial, followed by recording cellular and metabolic measurements. Insights were also provided on lymphoid/myeloid ratios, blood markers, and visceral and hepatic fat, which are secondary outcome measures and biomarkers associated with age-related diseases and aging generally. 

The biological age of participants was studied before and after they completed 3FMD cycles.

It is also important to note that the biological age and the chronological age may differ because aging is a heterogeneous process. Biological age is based on many multisystem biomarkers, which helps us understand the rate and level of organismal aging. 

Study findings

A calorie reduction of 15–20% below the normal levels was seen to have significant effects on the risk factors for multiple diseases. Preliminary findings showed that alternate-day fasting and caloric restriction (CR) are effective at reducing the risks related to aging. However, chronic CR is quite a severe intervention that could, in principle, reverse the benefits by reducing lean body mass and weight. 

The cohort comprised individuals who were healthier than the average American person. In this cohort, 3 FMD cycles were followed by a reduction in median biological age of 2.5 years. Furthermore, reductions in 20-year risk for cause-specific and all-cause mortality were noted.

The findings assume that the associations between mortality and biological age mirror the effect of change in biological age, but this fact is yet to be proven. Nevertheless, the results documented here offer early evidence of the potential health benefits of FMD, even in a cohort of relatively healthier individuals.

The benefits of FMD were most noted in individuals who were relatively more unhealthy at baseline. In terms of mechanisms, FMD lowered the hepatic fat fraction and visceral fat in study participants with non-alcoholic fatty liver disease and obesity. In this way, FMD cycles act to prevent diabetes and metabolic syndrome. Another explanation could be the importance of shared mechanisms, e.g., general rejuvenating effects in organs and cells, which lower systemic inflammation.

Conclusions

In sum, it was suggested that sustained FMD or similar dietary interventions may lead to improvements in population health by extending life expectancy, slowing the rate of aging, and reducing the risks of disease-specific mortality. More specifically, 3 FMD cycles each year could lead to a less than one year gain in biological age for every year increase in chronological age. 

A key limitation of the study centers around the small sample size and lack of heterogeneity in health status at baseline. Characteristics that study participants did not capture could change the impact of FMD on biological age, thereby making the current estimates inaccurate. Furthermore, extrapolation of the 3–6 months effects of the FMD to lifelong intervention should be interpreted with caution. This is because the effects may cease to persist if participants return to their pre-intervention lifestyles.