Circadian autophagy drives iTRF-mediated longevity

Sleep Hungry for Cellular Cleanup!

“…Collectively, these findings suggest that autophagy activity during the night/fasting period is necessary and sufficient for iTRF-mediated health and lifespan extension. In agreement, Ulgherait et al (2021) demonstrated that the enhanced longevity effect was a result of increased autophagy during the night/fasting phase using pharmacologically (RU486) inducible daGS-GAL4 system for atg1 overexpression. In contrast, day-specific fasting in RU-inducible atg1 overexpressed D. melanogaster did not extend the lifespan, further highlighting that the lifespan extension is enhanced by autophagy during night-specific fasting.…”

“…Considering the high homology between the genomes of Drosophila melanogaster and humans (Ugur et al, 2016), D. melanogaster has been used as an effective and useful model to investigate the significant modulators of TRF-mediated advantageous effects on healthspan (remaining healthier for longer) and lifespan (living longer) (Acosta-Rodriguez et al, 2021;Piper and Partridge, 2018;Suh et al, 2020). Ulgherait et al (2021) used genetically modified D. melanogaster under various fasting conditions to identify the crucial biological pathways that mediate improvement of health and longevity following intermittent TRF (iTRF). iTRF was defined as fasting from mid-morning for 20 h every alternate day with a recovery day of ad libitum diet between the fasting days.…”

“…In contrast, day-specific fasting in RU-inducible atg1 overexpressed D. melanogaster did not extend the lifespan, further highlighting that the lifespan extension is enhanced by autophagy during night-specific fasting. Ulgherait et al (2021) demonstrated that a functional circadian clock is necessary for the beneficial effects of iTRF. Furthermore, the study emphasizes the crucial role of enhanced autophagy during the night/fasting phase in the process of iTRF-associated improvements in health and lifespan.…”

“… Ulgherait et al (2021) used genetically modified D. melanogaster under various fasting conditions to identify the crucial biological pathways that mediate improvement of health and longevity following intermittent TRF (iTRF). iTRF was defined as fasting from mid-morning for 20 h every alternate day with a recovery day of ad libitum diet between the fasting days.…”

Autophagy takes it all – autophagy inducers target immune aging

“…These have been suggested to extend median and maximal lifespan, underpinned by in vivo and in vitro data obtained in various animal models (recently reviewed by Aman et al, 2021). Importantly, lifestyle and nutrition, particularly exercise (He et al, 2012) and dietary restriction (Hansen et al, 2018;Scott et al, 2004;Ulgherait et al, 2021) enhance the autophagy pathway. Several repurposed and already FDA-approved drugs that either inhibit mTORC1 or activate AMPK have recently gained considerable attention as promising immunoprotective interventions that could be translated into clinic within the next decade (Fig.…”