Different Genes Influence Lifespan in Male and Female Mice

This would be a good reason to transgender from male to female! (Caution: irony)

This research is in early stage.

"... evidence that genes directly control how long mice live—and that these genes have human orthologs. But female mice, which live longer than males, have different genes associated with longer life spans than male mice. ...
Looking across all the mice, the researchers pinpointed several genetic loci associated with longevity. They also linked several loci to longevity in female mice, but initially found none that were male-specific. However, when they took out data from male mice that died early in life, they turned up genes associated with longevity in male mice that were distinct from those in the female mice.  ...
The researchers stress that the dataset they’ve generated for mice is just a starting point ..."

From the abstract:

"INTRODUCTION

.... Despite advances in identifying aging pathways and drugs that extend life span in model systems, an integrative understanding of the interplay between genetics, sex, and environment in aging and life-span determination is largely lacking.

RATIONALE

... We set out to query genetic regulators of longevity in a total of 3276 UM-HET3 mice used in longevity studies by the National Institute on Aging’s Interventions Testing Program (NIA ITP). We interrogated whether the genetic basis of longevity is sex and age dependent, and whether nongenetic factors such as litter size and the effect of early access to nutrients on growth contribute to longevity determination. We characterized the age- and genotype-dependent changes in liver gene expression in mice from the same genetic cross. Finally, we integrated these results with orthogonal datasets to obtain a resource of prioritized candidate genetic loci and genes for further investigation.

RESULTS

When jointly analyzing males and females, we obtained a single, previously described, longevity locus on chromosome 12. However, when analyzed separately, males and females had distinct genetic determinants of longevity. In females, a single locus on chromosome 3 was uncovered, whereas in males, loci were detected only when early deaths were excluded, suggesting that some genetic variations had an effect on longevity beyond a certain age. Increased body weight associated with earlier death and some of the variation in adult body weight are explained by litter size. Hence, early access to nutrients may affect mouse longevity through its effect on growth. We used Mendelian randomization to replicate the relationships between early growth, adult size, and longevity in humans. To prioritize genes under the longevity loci, we profiled liver gene expression of adult and old mice to look for sex-, age-, and genetically driven differences in expression. Female livers had higher interferon-related gene expression, and older mice had overexpressed immune-related genes. Genetic regulation of gene expression was assessed, with the majority being conserved across sexes and age. ... validated some of the most highly scoring genes and identified Hipk1, Ddost, Hspg2, Fgd6, and Pdk1 as candidates.

CONCLUSION

This study provided insights into determinants of longevity, highlighting genetic mediators that can be sex or age specific, and nongenetic effects such as early access to nutrients. The combined body of information assembled from this study and the external data constitute a hypothesis-building resource for future studies on, and therapies for, aging, age-related disease, and longevity."

Different Genes Influence Lifespan in Male and Female Mice | The Scientist Magazine® Researchers say there may be similar, human genes whose effects on lifespan vary by sex.

Sex- and age-dependent genetics of longevity in a heterogeneous mouse population (open access)