Fig. 2: Aging-related pathways regulated by dietary interventions display circadian oscillations.

a Dietary interventions influence nutrient-sensing pathways⁵⁰ by inducing antiaging (yellow-green gradient) and reducing proaging (pink-purple gradient) molecules. There are known direct interactions between nutrient-sensing pathways involve in aging (SIRT1, AMPK, NAMPT, mTOR) and core clock genes (CLOCK/BMAL and PER/CRY). Several compounds known as caloric restriction mimetics (CRM, shown as gray font color) target specific nutrient-sensing genes and mimic the health benefits of CR without reducing food intake. CRMs tested by ITP and other laboratories include acarbose, curcumin, spermidine, rapamycin, metformin, resveratrol, NAD+ boosters and amino acids (reviewed by ref. ¹⁷²). CRMs (gray font color) are indicated next to or below their molecular targets. b Aging-related genes are expressed in a circadian manner (purple circles) in at least one tissue. Genes that are noncircadian in each tissue are represented as gray circles. RNA-seq and microarray containing circadian datasets for liver¹⁶ and other tissues extracted from CircaDB (http://circadb.hogeneschlab.org, Hogenesch laboratory). Proaging molecules: GH (growth hormone), GHR (growth hormone receptor), IGF-1 (insulin-like growth factor 1), PI3K (Phosphoinositide 3-kinase), AKT (also known as Protein kinase B), and mTOR (Mechanistic or Mammalian target of rapamycin). Antiaging molecules: SIRT1 (Sirtuin 1), AMPK (5’ AMP-activated protein kinase), PGC-1α (PPARγ co-activator 1a), PTEN (Phosphatase and tensin homolog), FOXO (Forkhead Box O). Core clock components CLOCK/BMAL1 (transcriptional activators) and PER/CRY (transcriptional repressors). See also Supplementary Table 1 for additional tissues and aging-related genes in mouse, baboon, and humans.