ArticleNature metabolism2019
MANF regulates metabolic and immune homeostasis in ageing and protects against liver damage.
Article in Nature metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
What it found
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Who cites it
75 citing papers in PubMed, 132 citations in OpenAlex.
- The role of mesencephalic astrocyte-derived neurotrophic factor in digestive diseases.Annals of medicine · 2026Review
- Spatial and functional characterization of ER stress proteins links fibroblast plasticity and proliferative processes in human osteoarthritic synovitis.Cell death and differentiation · 2026Article
- Modulation of the unfolded protein response with a C-terminal fragment of MANF facilitates recovery in models of multiple sclerosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Systematic identification of single transcription factor perturbations that drive cellular and tissue rejuvenation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Spatial transcriptomics analysis uncovers ER stress in MANF-deficient Purkinje cells underlying alcohol-induced cerebellar neurodegeneration in mice.Acta neuropathologica communications · 2025Article
- Electron Microscopy and Multi-Omics Reveal Mitochondrial Dysfunction and Structural Remodeling in the Hearts of Elderly Mice.Aging cell · 2025Article
- Maternal dietary fibre intake results in sex-specific single-cell molecular changes in the heart of the offspring.Clinical science (London, England : 1979) · 2025Article
- Impacts of systemic milieu on cerebrovascular and brain aging: insights from heterochronic parabiosis, blood exchange, and plasma transfer experiments.GeroScience · 2025Review
- Identification and validation of the pivotal role of MANF gene in pancreatic β-cell aging using bioinformatics.Biochemistry and biophysics reports · 2025Article
- Secreted proteins in treating metabolic dysfunction-associated steatotic liver disease: from bench towards bedside.Protein & cell · 2025Review
- Myeloid-derived MANF ameliorates ethanol-induced liver injury by enhancing microRNA-223 expression.Journal of gastroenterology · 2025Article
- Stem cell-based therapeutic strategies for liver aging.Liver research (Beijing, China) · 2025Review
- Paternal Obesity-Induced H3K27me3 Elevation Leads to MANF-Mediated Transgenerational Metabolic Dysfunction in Female Offspring.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Brain-acting hepatokines: its impact on energy balance and metabolism.Frontiers in neuroscience · 2025Review
- Unlocking the promise of MANF in diseases: Mechanistic insights and therapeutic potentials.Molecular biology reports · 2024Review
- The neurotrophic factor MANF regulates autophagy and lysosome function to promote proteostasis inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Aging insights from heterochronic parabiosis models.npj aging · 2024Review
- Race and Ethnicity, Socioeconomic Factors, and Epigenetic Age Acceleration in Survivors of Childhood Cancer.JAMA network open · 2024Article
- Rejuvenation of young blood on aging organs: Effects, circulating factors, and mechanisms.Heliyon · 2024Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Aging is accompanied by altered intercellular communication, deregulated metabolic function, and inflammation. Interventions that restore a youthful state delay or reverse these processes, prompting the search for systemic regulators of metabolic and immune homeostasis. Here we identify MANF, a secreted stress-response protein with immune modulatory properties, as an evolutionarily conserved regulator of systemic and in particular liver metabolic homeostasis. We show that MANF levels decline with age in flies, mice and humans, and MANF overexpression extends lifespan in flies. MANF deficient flies exhibit enhanced inflammation and shorter lifespans, and MANF heterozygous mice exhibit inflammatory phenotypes in various tissues, as well as progressive liver damage, fibrosis, and steatosis. We show that immune cell-derived MANF protects against liver inflammation and fibrosis, while hepatocyte-derived MANF prevents hepatosteatosis. Liver rejuvenation by heterochronic parabiosis in mice further depends on MANF, while MANF supplementation ameliorates several hallmarks of liver aging, prevents hepatosteatosis induced by diet, and improves age-related metabolic dysfunction. Our findings identify MANF as a systemic regulator of homeostasis in young animals, suggesting a therapeutic application for MANF in age-related metabolic diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.