Dataset Information

OXR1 maintains the retromer to delay brain aging under dietary restriction.

ABSTRACT: Dietary restriction (DR) delays aging, but the mechanism remains unclear. We identified polymorphisms in mtd, the fly homolog of OXR1, which influenced lifespan and mtd expression in response to DR. Knockdown in adulthood inhibited DR-mediated lifespan extension in female flies. We found that mtd/OXR1 expression declines with age and it interacts with the retromer, which regulates trafficking of proteins and lipids. Loss of mtd/OXR1 destabilized the retromer, causing improper protein trafficking and endolysosomal defects. Overexpression of retromer genes or pharmacological restabilization with R55 rescued lifespan and neurodegeneration in mtd-deficient flies and endolysosomal defects in fibroblasts from patients with lethal loss-of-function of OXR1 variants. Multi-omic analyses in flies and humans showed that decreased Mtd/OXR1 is associated with aging and neurological diseases. mtd/OXR1 overexpression rescued age-related visual decline and tauopathy in a fly model. Hence, OXR1 plays a conserved role in preserving retromer function and is critical for neuronal health and longevity.

SUBMITTER: Wilson KA

PROVIDER: S-EPMC10784588 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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OXR1 maintains the retromer to delay brain aging under dietary restriction.

Wilson Kenneth A KA Bar Sudipta S Dammer Eric B EB Carrera Enrique M EM Hodge Brian A BA Hilsabeck Tyler A U TAU Bons Joanna J Brownridge George W GW Beck Jennifer N JN Rose Jacob J Granath-Panelo Melia M Nelson Christopher S CS Qi Grace G Gerencser Akos A AA Lan Jianfeng J Afenjar Alexandra A Chawla Geetanjali G Brem Rachel B RB Campeau Philippe M PM Bellen Hugo J HJ Schilling Birgit B Seyfried Nicholas T NT Ellerby Lisa M LM Kapahi Pankaj P

Nature communications 20240111 1

Dietary restriction (DR) delays aging, but the mechanism remains unclear. We identified polymorphisms in mtd, the fly homolog of OXR1, which influenced lifespan and mtd expression in response to DR. Knockdown in adulthood inhibited DR-mediated lifespan extension in female flies. We found that mtd/OXR1 expression declines with age and it interacts with the retromer, which regulates trafficking of proteins and lipids. Loss of mtd/OXR1 destabilized the retromer, causing improper protein trafficking ...[more]

PMID: 38212606

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Project description:The Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet seems a promising approach to preserve brain function during aging. Previous systematic reviews have demonstrated benefits of the MIND diet for cognition and dementia, though an update is needed. Additionally, other outcomes relevant to brain aging have not been summarized. Therefore, this systematic review aims to give an up-to-date and complete overview on human studies that examined the MIND diet in relation to brain aging outcomes in adults aged ≥40 y. Ovid Medline, Web of Science core collection, and Scopus were searched up to July 25, 2023. Study quality was assessed using the Newcastle-Ottawa Scale and the Cochrane Risk-of-Bias tool. We included 40 articles, of which 32 were unique cohorts. Higher MIND diet adherence was protective of dementia in 7 of 10 cohorts. Additionally, positive associations were demonstrated in 3 of 4 cohorts for global cognition and 4 of 6 cohorts for episodic memory. The protective effects of the MIND diet on cognitive decline are less apparent, with only 2 of 7 longitudinal cohorts demonstrating positive associations for global decline and 1 of 6 for episodic memory decline. For other brain outcomes (domain-specific cognition, cognitive impairments, Parkinson's disease, brain volume, and pathology), results were mixed or only few studies had been performed. Many of the cohorts demonstrating protective associations were of North American origin, raising the question if the most favorable diet for healthy brain aging is population-dependent. In conclusion, this systematic review provides observational evidence for protective associations between the MIND diet and global cognition and dementia risk, but evidence for other brain outcomes remains mixed and/or limited. The MIND diet may be the preferred diet for healthy brain aging in North American populations, though evidence for other populations seems less conclusive. This review was registered at PROSPERO as CRD42022254625.

Dataset Information

OXR1 maintains the retromer to delay brain aging under dietary restriction.

Publications

OXR1 maintains the retromer to delay brain aging under dietary restriction.

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