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Ageing underlies functional decline of the brain and is the primary risk factor for several neurodegenerative conditions, including Alzheimer's disease (AD). However, the molecular mechanisms that cause functional decline of the brain during ageing, and how these contribute to AD pathogenesis, are not well understood. The objective of this study was to identify biological processes that are altered during ageing in the hippocampus and that modify Ad risk and lifespan, and then to identify putative gene drivers of these programmes.
View Article and Find Full Text PDFSNP rs6543176 is associated with extreme human longevity but increased risk for cancer.
Geroscience
January 2025
Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, 02111, USA.
Using whole-genome sequencing (WGS) might offer insights into rare genetic variants associated with healthy aging and extreme longevity (EL), potentially pointing to useful therapeutic targets. In this study, we conducted a genome-wide association study using WGS data from the Long Life Family Study and identified a novel longevity-associated variant rs6543176 in the SLC9A2 gene. This SNP also showed a significant association with reduced hypertension risk and an increased, though not statistically significant, cancer risk.
View Article and Find Full Text PDFHealthy longevity-associated protein improves cardiac function in murine models of cardiomyopathy with preserved ejection fraction.
Cardiovasc Diabetol
November 2024
Bristol Medical School, Translational Health Sciences, University of Bristol, Upper Maudlin St, Bristol, BS2 8HW, UK.
Aims: Aging is influenced by genetic determinants and comorbidities, among which diabetes increases the risk for heart failure with preserved ejection fraction. There is no therapy to prevent heart dysfunction in aging and diabetic individuals. In previous studies, a single administration of the longevity-associated variant (LAV) of the human BPIFB4 gene halted heart decline in older and type 2 diabetic mice.
View Article and Find Full Text PDFExploring the Relationship of rs2802292 with Diabetes and NAFLD in a Southern Italian Cohort-Nutrihep Study.
Int J Mol Sci
September 2024
Medical Genetics, National Institute of Gastroenterology, IRCCS "Saverio de Bellis" Research Hospital, 70013 Castellana Grotte, Italy.
The minor G-allele of FOXO3 rs2802292 is associated with human longevity. The aim of this study was to test the protective effect of the variant against the association with type 2 Diabetes and NAFLD. rs2802292 was genotyped in a large population of middle-aged subjects (n = 650) from a small city in Southern Italy.
View Article and Find Full Text PDFGenetic associations with human longevity are enriched for oncogenic genes.
medRxiv
August 2024
Quantitative Sciences Unit, Department of Medicine, Stanford University, Stanford, CA, 94304, USA.
Human lifespan is shaped by both genetic and environmental exposures and their interaction. To enable precision health, it is essential to understand how genetic variants contribute to earlier death or prolonged survival. In this study, we tested the association of common genetic variants and the burden of rare non-synonymous variants in a survival analysis, using age-at-death (N = 35,551, median [min, max] = 72.
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