DAF-16/FOXO Transcription Factor in Aging and Longevity

Abstract

Aging is associated with age-related diseases and an increase susceptibility of cancer. Dissecting the molecular mechanisms that underlie aging and longevity would contribute to implications for preventing and treating the age-dependent diseases or cancers. Multiple signaling pathways such as the insulin/IGF-1 signaling pathway, TOR signaling, AMPK pathway, JNK pathway and germline signaling have been found to be involved in aging and longevity. And DAF-16/FOXO, as a key transcription factor, could integrate different signals from these pathways to modulate aging, and longevity via shuttling from cytoplasm to nucleus. Hence, understanding how DAF-16/FOXO functions will be pivotal to illustrate the processes of aging and longevity. Here, we summarized how DAF-16/FOXO receives signals from these pathways to affect aging and longevity. We also briefly discussed the transcriptional regulation and posttranslational modifications of DAF-16/FOXO, its co-factors as well as its potential downstream targets participating in lifespan according to the published data in C. elegans and in mammals, and in most cases, we may focus on the studies in C. elegans which has been considered to be a very good animal model for longevity research.

Saponin‐rich extracts fromHolothuria leucospilotamediate lifespan extension and stress resistance inCaenorhabditis elegansviadaf‐16

“…Anti‐microbial proteins also exhibit a second set of potential lifespan effectors in C. elegans. Previous study has shown that gene encoding for anti‐bacterial lysosomes ( lys‐7 ) is upregulated in daf‐2 null mutant, which can also upregulate during Serratia marcescens pathogenic infection (Sun, Chen, & Wang, ). Metallothionein (MT) is a low molecular weight anti‐apoptotic protein that has been shown to scavenge free radical involving stress sensitive pathway in C. elegans and mice.…”

Xanthigen® reduces lipid deposition and improves stress resistance in Caenorhabditis elegans

“…DAF-16 plays a role in both oxidative and heat stress as well as starvation. It is the sole orthologous of the FOXO family of transcription factors in C. elegans and DAF-16/FOXO proteins are a family of transcription factors that integrate different signals by phosphorylation of proteins including insulin/IGF-1, TOR, AMPK, or JNK pathways to modulate important processes, via shuttling from cytoplasm to nucleus, and the expression of genes that influence in cell growth, proliferation, differentiation, or longevity 25 . Under these circumstances, cytosolic DAF-16 protein is phosphorylated and then it relocates to the nuclei and promotes both the expression of genes that confer resistance to stress and longevity.…”

The Chemistry, Pharmacology and Therapeutic Potential of the Edible Mushroom Dictyophora indusiata (Vent ex. Pers.) Fischer (Synn. Phallus indusiatus)

“…This transcription factor is involved in diverse cellular function including the regulation cell death or apoptosis, resistance to oxidative stress and increased life span. Good references for the regulation of these transcription factors are available [54][55][56]. Hence, transcription factors that are critically involved in alleviation of oxidative stress and increased life span of C. elgans are activated by D. indusiata polysaccharides.…”