biostudies-literatureBeaudoin-Chabot CMinistry of Health -SingaporeMinistry of Education - SingaporeNIH HHS5889https://www.ebi.ac.uk/biostudies/studies/S-EPMC9582010biostudies-literatureUnknown13(1)Metabolic diseases often share common traits, including accumulation of unfolded proteins in the endoplasmic reticulum (ER). Upon ER stress, the unfolded protein response (UPR) is activated to limit cellular damage which weakens with age. Here, we show that Caenorhabditis elegans fed a bacterial diet supplemented high glucose at day 5 of adulthood (HGD-5) extends their lifespan, whereas exposed at day 1 (HGD-1) experience shortened longevity. We observed a metabolic shift only in HGD-1, while glucose and infertility synergistically prolonged the lifespan of HGD-5, independently of DAF-16. Notably, we identified that UPR stress sensors ATF-6 and PEK-1 contributed to the longevity of HGD-5 worms, while ire-1 ablation drastically increased HGD-1 lifespan. Together, we postulate that HGD activNature communicationsThe unfolded protein response reverses the effects of glucose on lifespan in chemically-sterilized C. elegans.PMC9582010MOH-0005662019-T1-002-011P40 OD0104402018-T2-1-002Abdul Khalid ATCelik CLim VWXBeaudoin-Chabot CXu SLow ADKoh JHThibault GWang LThalappilly SfalseThe unfolded protein response reverses the effects of glucose on lifespan in chemically-sterilized C. elegans.Metabolic diseases often share common traits, including accumulation of unfolded proteins in the endoplasmic reticulum (ER). Upon ER stress, the unfolded protein response (UPR) is activated to limit cellular damage which weakens with age. Here, we show that Caenorhabditis elegans fed a bacterial diet supplemented high glucose at day 5 of adulthood (HGD-5) extends their lifespan, whereas exposed at day 1 (HGD-1) experience shortened longevity. We observed a metabolic shift only in HGD-1, while glucose and infertility synergistically prolonged the lifespan of HGD-5, independently of DAF-16. Notably, we identified that UPR stress sensors ATF-6 and PEK-1 contributed to the longevity of HGD-5 worms, while ire-1 ablation drastically increased HGD-1 lifespan. Together, we postulate that HGD activ2022-01-01T00:00:00Z2022 Oct2026-05-27T11:36:08.315Z2024-11-20T11:22:22.83ZS-EPMC95820103626141510.1038/s41467-022-33630-0