Human Islet miR-199a-5p and miR-214-3p Associate With Donor Age, BMI, and Sex and Mediate Cellular Aging in Islet-Derived Cells.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος:	Human Islet miR-199a-5p and miR-214-3p Associate With Donor Age, BMI, and Sex and Mediate Cellular Aging in Islet-Derived Cells.
Συγγραφείς:	Wong WKM; Diabetes & Islet Biology Group, School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia., El-Azzi I; Diabetes & Islet Biology Group, School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia., Nachanekar A; Diabetes & Islet Biology Group, School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia., Alvandi E; Diabetes & Islet Biology Group, School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia., Pham NHT; Diabetes & Islet Biology Group, School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia., Hardikar HP; Diabetes & Islet Biology Group, School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia., Polkamp M; Diabetes & Islet Biology Group, School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia., Saini V; Diabetes & Islet Biology Group, School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia., Cheng F; Health Medicine Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China., Jiang G; Department of Medicine and Therapeutics, And Hong Kong Institute of Diabetes and Obesity, and Li Ka Shing Institute of Health Sciences, the Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong (Special Administrative Region), China.; School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-Sen University, Shenzhen, Guangdong, China., Sørensen AE; Department of Science and Environment, Roskilde University, Roskilde, Denmark., Chew YV; Centre for Transplant and Renal Research, Westmead Institute for Medical Research (WIMR), University of Sydney, Westmead, New South Wales, Australia., Thomas HE; Immunology and Diabetes Group, St. Vincent's Institute (SVI) for Medical Research, Fitzroy, Victoria, Australia., Loudovaris T; Immunology and Diabetes Group, St. Vincent's Institute (SVI) for Medical Research, Fitzroy, Victoria, Australia., Ma RCW; Department of Medicine and Therapeutics, And Hong Kong Institute of Diabetes and Obesity, and Li Ka Shing Institute of Health Sciences, the Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong (Special Administrative Region), China., Hawthorne WJ; Centre for Transplant and Renal Research, Westmead Institute for Medical Research (WIMR), University of Sydney, Westmead, New South Wales, Australia., Dalgaard LT; Department of Science and Environment, Roskilde University, Roskilde, Denmark., Joglekar MV; Diabetes & Islet Biology Group, School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia., Hardikar AA; Diabetes & Islet Biology Group, School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia.; Department of Science and Environment, Roskilde University, Roskilde, Denmark.
Πηγή:	Acta physiologica (Oxford, England) [Acta Physiol (Oxf)] 2026 Aug; Vol. 242 (8), pp. e70277.
Τύπος έκδοσης:	Journal Article
Γλώσσα:	English
Στοιχεία περιοδικού:	Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101262545 Publication Model: Print Cited Medium: Internet ISSN: 1748-1716 (Electronic) Linking ISSN: 17481708 NLM ISO Abbreviation: Acta Physiol (Oxf) Subsets: MEDLINE
Imprint Name(s):	Publication: Oxford : Wiley-Blackwell Original Publication: Oxford : Blackwell Pub., c2006-4
Ιατρικοί όροι (MeSH):	MicroRNAs/metabolism , MicroRNAs/genetics , Islets of Langerhans/metabolism , Islets of Langerhans/cytology , Cellular Senescence/physiology , Cellular Senescence/genetics , Body Mass Index*, Humans ; Female ; Male ; Adult ; Middle Aged ; Aged ; Age Factors ; Sex Factors ; Tissue Donors
Περίληψη:	Objectives: Human islets are widely researched to understand pathophysiological mechanisms leading to diabetes. Sex, age, and body mass index (BMI) are key donor traits influencing islet function, which is also regulated by an intricate network of microRNAs. Methods: Here, we profiled 754 microRNAs and 58 191 gene transcripts (19 919 protein-coding) in up to 131 different human islet donor preparations (without diabetes) and assessed their association with donor traits. Additionally, the effect of the age-associated key microRNAs on relative telomere length in human islet-derived cells was evaluated. Results: MicroRNA discovery analyses identified miR-199a-5p and miR-214-3p to be associated (adjusted p-value ≤ 0.05) with all three traits (i.e., sex, age, and BMI); miR-147b-3p with sex and age; miR-378a-5p with sex and BMI; miR-542-3p, miR-34a-3p, miR-34a-5p, miR-497-5p and miR-99a-5p with age and BMI. After adjusting for covariates, 612 protein-coding gene transcripts associated with sex (excluding those from sex-chromosomes), 902 with age, and 250 with BMI. MicroRNA-199a-5p and miR-214-3p levels negatively correlated with mRNAs critical in islet function, metabolic regulation, and senescence. In vitro validation studies verified that inhibition of two common microRNAs (miR-199a-5p/-214-3p) slowed down telomere length shortening in human islet-derived cells. Conclusions: Our analyses identify human islet microRNAs associated with donor traits and provide evidence that these microRNAs can potentially modulate cellular aging phenotype (reflected by relative telomere length) in human islet-derived cells. (© 2026 The Author(s). Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)
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Grant Information:	FT110100254 Australian Research Council Future Fellowship; JDRF/4-CDA2016-228-MB United States JDRF Breakthrough T1D; 3-PDF-2023-1324-A-N United States JDRF Breakthrough T1D; FLACK-2016-17 Marian and E.H. Flack Trust; NNF17SA0031406 Novo Nordisk Fonden; Leona M. and Harry B. Helmsley Charitable Trust; Western Sydney University and Ainsworth Foundation; T12-402/13N Research Grants Council (RGC) of Hong Kong; R4012-18 Research Grants Council (RGC) of Hong Kong; Chinese University of Hong Kong; Rebecca L. Cooper Medical Research Foundation; Ingham Institute for Applied Medical Research; Australian Government Research Training Program Scholarship; Danish Diabetes & Endocrine Academy; Government of Victoria
Contributed Indexing:	Keywords: BMI; age; islet; mRNA; microRNA; sex
Substance Nomenclature:	0 (MicroRNAs) 0 (mirn199 microRNA, human) 0 (MIRN214 microRNA, human)
Entry Date(s):	Date Created: 20260726 Date Completed: 20260726 Latest Revision: 20260728
Update Code:	20260728
PubMed Central ID:	PMC13401865
DOI:	10.1111/apha.70277
PMID:	42502989
Βάση Δεδομένων:	MEDLINE

Περιγραφή
ISSN:	1748-1716
DOI:	10.1111/apha.70277