The effect of prolonged intermittent fasting on autophagy, inflammasome and senescence genes expressions: An exploratory study in healthy young males

Intermittent fasting (IF) has been associated with longevity and healthspan through autophagy and reduction of inflammation activity. The senescence process is linked with autophagy activity and determines the organ age as chronological age. The effect of prolonged IF on autophagy, inflammasome activity, and senescence needs to be elucidated further. Twenty-five healthy young males were recruited and performed 17–19 h/day fasting for 30 days. Blood samples were collected one week before (TP1), two weeks after the start (TP2), one month after the start (TP3), and one week after the end (TP4) of the IF and extracted to obtain mRNA to determine autophagy (ATG5, ULK1, and BECN1), inflammasome (NLRP3, IL-1 β, ASC, and TNF- α), and senescence (p16INK4A, p21, and P53) marker expression level by qPCR. Prolonged IF induced expression level of ATG5, ULK1 and BECN1 at TP2 but decreased at TP4. The NLRP3 and IL-1β expression level increased at TP2 and TP3, but decreased at TP4. ASC expression level increased at TP2, decreased at TP3 and returned to normal at TP4. Prolonged IF kept reducing TNF-α expression level until TP4. The expression level of p16INK4A and p21 tended to decrease over the time of observation. The expression level of P53 increased at TP2 and TP3 but decreased at TP4. Our study showed that prolonged IF affects the activities of autophagy, inflammasome, and senescence in a time-dependent manner. Throughout observational time, prolonged intermittent fasting affected dynamical changes in autophagy, senescence and inflammasome activities. These include:•Prolonged intermittent fasting significantly induced ATG5 and ULK1 expression but reduced the other autophagy gene, BCN1.•Prolonged intermittent fasting significantly induced the expression of inflammasome gene NLRP3 and IL-1β but not its active component, ASC.•Prolonged intermittent fasting could significantly reduce p21, p16 and p53 expression at a later time point. Taken together, this manuscript combines novelty and clinical relevance to help our understanding of fasting, especially intermittent fasting. Furthermore, it can be implemented as a non-pharmacological and low-cost therapy to promote rejuvenation.