Importance of circadian timing for aging and longevity

Dietary restriction (DR) decreases body weight, improves health, and extends lifespan. DR can be achieved by controlling how much and/or when food is provided, as well as by adjusting nutritional composition. Because these factors are often combined during DR, it is unclear which are necessary for beneficial effects. Several drugs have been utilized that target nutrient-sensing gene pathways, many of which change expression throughout the day, suggesting that the timing of drug administration is critical.

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Fig: Crosstalk between molecular components of circadian clock, nutrient-sensing, and metabolic pathways: Core clock proteins CLOCK/BMAL1 (transcriptional activators) and PER/CRY (repressors) are engaged in an autoregulatory transcriptional/translational feedback loop leading to 24 h oscillations in gene expression, activity and protein levels. The molecular clock also regulates the rhythmic expression of genes involved in several cellular functions and nutrient-sensing pathways, which in turn feedback to the core clock machinery. CLOCK (Clock), BMAL1 (Arntl), PER (Period), CRY (Cryptochrome), SIRT1 (Sirtuin 1), AMPK (5’ AMP-activated protein kinase), PGC-1α (PPARγ co-activator 1a), mTOR (Mammalian target of rapamycin), ROR (RAR- Related Orphan Receptor), Rev-Erb (Nr1d1), and PPAR (Peroxisome Proliferator Activated Receptor).

Here, we discuss how dietary and pharmacological interventions promote a healthy lifespan by influencing energy intake and circadian rhythms.

Acosta-Rodríguez, V.A., Rijo-Ferreira, F., Green, C.B. et al. Importance of circadian timing for aging and longevity. Nat Commun 12, 2862 (2021). https://doi.org/10.1038/s41467-021-22922-6

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