Abstract
SummaryIntermittent fasting (IF) can improve function and health during aging in laboratory model organisms, but the mechanisms at work await elucidation. We subjected fruit flies (Drosophila melanogaster) to varying degrees of IF and found that just one month of a 2-day fed:5-day fasted IF regime at the beginning of adulthood was sufficient to extend lifespan. This long-lasting, beneficial effect of early IF was not due to reduced fecundity. Starvation resistance and resistance to oxidative and xenobiotic stress were increased after IF. Early-life IF also led to higher lipid content in 60-day-old flies, a potential explanation for increased longevity. Guts of flies 40 days post-IF showed a significant reduction in age-related pathologies and improved gut barrier function. Improved gut health was also associated with reduced relative bacterial abundance. Early IF thus induced profound long-term changes. Pharmacological and genetic epistasis analysis showed that IF acted independently of the TOR pathway because rapamycin and IF acted additively to extend lifespan, and global expression of a constitutively active S6K did not attenuate the IF-induced lifespan extension. We conclude that short-term IF during early life can induce long-lasting beneficial effects, with robust increase in lifespan in a TOR-independent manner, probably at least in part by preserving gut health.
Highlights
Intermittent fasting (IF), an umbrella term for diets that cycle between a period of fasting and non-fasting, has become increasingly popular as a weight loss regime (e.g., ‘‘everyother-day fasting’’ and the ‘‘5:2’’ diet) [1, 2]
IF during Early Life Extends Lifespan We hypothesized that the periods of starvation in previously published IF regimes may have been insufficient in duration to influence survival [26]
We began by fasting female flies by exposing them to nutrient-free agar gel for 5 consecutive days per week (5-day IF—the 2:5 diet) throughout life and found that this led to earlier onset of age-related mortality and significantly shortened lifespan compared to ad-libitum-fed controls (Figure 1A)
Summary
Intermittent fasting (IF), an umbrella term for diets that cycle between a period of fasting and non-fasting, has become increasingly popular as a weight loss regime (e.g., ‘‘everyother-day fasting’’ and the ‘‘5:2’’ diet) [1, 2]. One study on the clinical outcomes of fasting in young overweight women described significant weight loss as a result of the IF regime, as well as reduced fat mass and waist circumference, and lowered serum cholesterol, triglycerides, and C-reactive protein [4]. Pilot, clinical trials used a fasting mimicking diet (FMD) (consisting of monthly cycles of a 5-day fast during which daily food intake was reduced to $50% normal caloric intake), which reduced multiple health risk factors during the post-fast recovery period, including lowered blood pressure, and reduced blood glucose and insulin-like growth factor-1 (IGF-1) levels [5, 6]. FMD was recently found to increase pancreatic b cell regeneration in mouse models of diabetes [22]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
