PMID- 34397058 OWN - NLM STAT- MEDLINE DCOM- 20220125 LR - 20220125 IS - 2042-650X (Electronic) IS - 2042-6496 (Linking) VI - 12 IP - 19 DP - 2021 Oct 4 TI - DAF-16 acts as the "hub" of astaxanthin's anti-aging mechanism to improve aging-related physiological functions in Caenorhabditis elegans. PG - 9098-9110 LID - 10.1039/d1fo01069g [doi] AB - Astaxanthin (AX) is a xanthophyll carotenoid that can effectively inhibit the production of peroxides and thereby protect the body from oxidative damage. In recent years, AX had been shown to have anti-aging properties, both in vivo and in vitro. However, the underlying mechanisms by which AX regulates senescence related proteins and signaling pathways remain unclear. Therefore, we used Caenorhabditis elegans (C. elegans) model binding proteomics to reveal AX anti-aging activity and its molecular mechanism. Our results suggest that AX promotes the health and lifespan of C. elegans by improving mobility, reducing the accumulation of age pigments, and increasing resistance to heat stress. In terms of the underlying mechanism, AX helps prolong the life of worms by regulating AGE-1 in the insulin signaling pathway, promoting the transport of DAF-16 into the nucleus and then up-regulating the expression level of DAF-16's downstream proteins (such as superoxide dismutase [Mn] 2 (SOD-3), heat shock proteins (HSPs), glutathione s-transferase (GST-4), etc.). Furthermore, AX may be a relevant response target for activation of dietary restriction pathways in vivo as a dietary restriction mimic. Meanwhile, proteomics data confirmed that there were 15 proteins enriched in the longevity regulation pathway. AX mainly regulates oxidative stress and the aging process by modulating the insulin signaling pathway around DAF-16 as the "hub". In addition to the insulin signaling pathway, other pathways including dietary restriction, AMP-activated protein kinase (AMPK), and mammal target of rapamycin (mTOR) are also dependent on DAF-16. These findings expand and deepen our knowledge of the underlying mechanism by which AX extends the lifespan of C. elegans. FAU - Liu, Xiaojuan AU - Liu X AUID- ORCID: 0000-0003-2435-5837 AD - Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Science, South China Agricultural University, Guangzhou, 510642, Guangdong, China. liuxj@scau.edu.cn. AD - Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China. FAU - Liu, Han AU - Liu H AD - Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Science, South China Agricultural University, Guangzhou, 510642, Guangdong, China. liuxj@scau.edu.cn. AD - Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China. FAU - Chen, Zhiqing AU - Chen Z AD - Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Science, South China Agricultural University, Guangzhou, 510642, Guangdong, China. liuxj@scau.edu.cn. AD - Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China. FAU - Xiao, Jie AU - Xiao J AUID- ORCID: 0000-0002-4718-1174 AD - Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Science, South China Agricultural University, Guangzhou, 510642, Guangdong, China. liuxj@scau.edu.cn. AD - Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China. FAU - Cao, Yong AU - Cao Y AUID- ORCID: 0000-0002-8334-5324 AD - Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Science, South China Agricultural University, Guangzhou, 510642, Guangdong, China. liuxj@scau.edu.cn. AD - Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China. LA - eng PT - Journal Article DEP - 20211004 PL - England TA - Food Funct JT - Food & function JID - 101549033 RN - 0 (Caenorhabditis elegans Proteins) RN - 0 (Forkhead Transcription Factors) RN - 0 (Insulin) RN - 0 (Xanthophylls) RN - 0 (daf-16 protein, C elegans) RN - 8XPW32PR7I (astaxanthine) RN - EC 1.15.1.1 (Sod-3 protein, C elegans) RN - EC 1.15.1.1 (Superoxide Dismutase) SB - IM MH - Aging/drug effects MH - Animals MH - Caenorhabditis elegans/drug effects/genetics/*physiology MH - Caenorhabditis elegans Proteins/genetics/*metabolism MH - Cell Nucleus/metabolism MH - Cytosol/metabolism MH - Forkhead Transcription Factors/*metabolism MH - Gene Expression MH - Insulin/metabolism MH - Longevity/*drug effects MH - Mutation MH - Proteomics MH - Signal Transduction/drug effects MH - Stress, Physiological/drug effects MH - Superoxide Dismutase/genetics/metabolism MH - Xanthophylls/pharmacology EDAT- 2021/08/17 06:00 MHDA- 2022/01/27 06:00 CRDT- 2021/08/16 08:50 PHST- 2021/08/17 06:00 [pubmed] PHST- 2022/01/27 06:00 [medline] PHST- 2021/08/16 08:50 [entrez] AID - 10.1039/d1fo01069g [doi] PST - epublish SO - Food Funct. 2021 Oct 4;12(19):9098-9110. doi: 10.1039/d1fo01069g.