Catherine Cheng, a student in the Biology of Aging track of the Integrated Multidisciplinary Graduate Program, now called Integrated Biomedical Sciences program, has just published her first author paper online in Aging Cell.
The title of the paper is “Genetically heterogeneous mice exhibit a female survival advantage that is age- and site-specific: results from a large multi-site study.” The study uses data from the National Institute on Aging Interventions Testing Program (ITP), a multi-institutional study that was initiated in 2004as a collaborative effort between UT Health San Antonio’s Barshop Institute for Longevity and Aging Studies, the University of Michigan and The Jackson Laboratory.
“The female survival advantage is a robust characteristic of human longevity. However, underlying mechanisms are not understood,” explained Cheng. “A problem faced by the field is that traditional rodent models, which are predominantly inbred strains, do not reliably exhibit a female survival advantage.”
Cheng explained that the genetically heterogeneous mouse model used by the National Institute on Aging Interventions Testing Program, on the other hand, shows a persistent female survival advantage observed at three geographically distinct sites and in six separate cohorts over a 10-year period.
“In our study, we use a different approach to survival analysis. Instead of comparing median lifespan or overall survival using the familiar Kaplan-Meier analysis, we use a method of instantaneous mortality hazard estimation, which allows us to characterize survival dynamics in much higher resolution than before.”
Cheng explained that this technique is made possible by the availability of the very large sample sizes from the ITP dataset. In this paper, she used survival data from 3,690 animals, the untreated controls. However, data is available for 15,765 animals in total.
“The ITP really is a rich resource in that regard. What we found in this paper is that the female survival advantage is greatest in early adulthood, peaking around 350 days of age and diminishing progressively thereafter. That corresponds to an eight-fold greater mortality rate in males than in females, all before one year of age.”
For Cheng, this discovery was interesting from a biological standpoint, because the ITP protocol specifically censors deaths due to fighting between the mice, suggesting that there may be biological factors, rather than behavioral factors, at play.
She also looked at the effects of a few other factors (bodyweight and study site variation), and found that male survival is significantly more variable in response to those changes.
“Altogether, we show that this mouse model recapitulates some key characteristics of the human female survival advantage, underscoring its potential for interrogating the basis for human sex differences in aging.”