Sex- and age-dependent genetics of longevity in a heterogeneous mouse population.
Maroun Bou SleimanSuheeta RoyArwen W GaoMarie C SadlerGiacomo V G von AlvenslebenHao LiSaunak SenDavid E HarrisonJames F NelsonRandy StrongRichard A MillerZoltán KutalikRobert W WilliamsJohan AuwerxPublished in: Science (New York, N.Y.) (2022)
DNA variants that modulate life span provide insight into determinants of health, disease, and aging. Through analyses in the UM-HET3 mice of the Interventions Testing Program (ITP), we detected a sex-independent quantitative trait locus (QTL) on chromosome 12 and identified sex-specific QTLs, some of which we detected only in older mice. Similar relations between life history and longevity were uncovered in mice and humans, underscoring the importance of early access to nutrients and early growth. We identified common age- and sex-specific genetic effects on gene expression that we integrated with model organism and human data to create a hypothesis-building interactive resource of prioritized longevity and body weight genes. Finally, we validated Hipk1 , Ddost , Hspg2 , Fgd6 , and Pdk1 as conserved longevity genes using Caenorhabditis elegans life-span experiments.
Keyphrases
- genome wide
- gene expression
- body weight
- high fat diet induced
- copy number
- drosophila melanogaster
- dna methylation
- healthcare
- physical activity
- public health
- endothelial cells
- wild type
- machine learning
- cell free
- circulating tumor
- electronic health record
- quality improvement
- single molecule
- genome wide identification
- middle aged
- genome wide association study