A new vertebrate model to study the role of growth factors IGF1 and IGF2 in sex dimorphism of longevity and aging.
Women live longer than men, and different age-related diseases afflict women and men. Our poor understanding of the basis of these sex-differences promote disparities between men and women in the success of treatments of age-related diseases. The Insulin and Insulin-like Signaling (IIS) molecular pathway is known to regulate longevity. This project is aimed at understanding how specific hormones in the IIS pathway regulate the aging process within the cell and the organism. We hope to better define the processes of how males and females age differently so that treatments and therapies can be designed to be more effective within a sex, and promote healthy aging across both sexes.
The overall goal of this research is to test if hormones that regulate the IIS pathway contribute to sexual dimorphism in longevity and aging. Research on one of these hormones, IGF2, has been limited by the lack of an animal model that naturally expresses IGF2 in adulthood. To overcome this barrier, we are using brown anole lizard, which we have found naturally expresses IGF2 through adulthood similarly to humans (Beatty and Schwartz 2020).
This research and developed methodology will open new avenues of research, currently unattainable with our standard model systems, on IGF2 and other top regulators of the IIS pathway that play a role in the natural processes of aging. Through this research we train undergraduate researchers in collecting and analyzing organismal and molecular data. The data from this research is also being incorporated into the Functional Genomics course for teaching hands-on-analysis of RNAseq datasets in the context of aging.
The Research Aims
1. We are conducting a longitudinal aging experiment using brown anole lizards to define the respective roles of IGF1 and IGF2 in sex-specific aging. Our objectives are to:
(a) characterize the brown anole as a complementary model organism for comparative biology of aging, particularly for the top regulators of IIS; and
(b) experimentally test if increased IGF1 or IGF2 can increase the rate of aging and contribute to sex differences in longevity and aging.
2. We are using reptile cell culture experiments to test whether male cellular environment is pro-aging, and if sex differences in IIS signaling become programmed with age. Our objective is to:
(a) use age-of-donor cell culture experiments to partition the sex chromosome effects of sexual dimorphism in cellular senescence; and
(b) to determine if longer exposure to an internal male environment increasingly programs cells to age in sex dimorphic ways, and more specifically program the IIS network to be stimulated in sex dimorphic ways.
PIs: Tonia Schwartz, Rita Graze, Aaron Reedy
Graduate Students: Abby Beatty, Amanda Clark, Ryan Harding, Ruksana Amin
Undergraduate Researchers: Milica Courtenay, Holder Smith, Kimberly Glenn, Callista Beaumont, Taylor McKibbin, Megan Benedict, Alexis Lindsey
Collaborators: Robert Cox, Dasia Simpson, Randy Klabacka
This research is supported by the National Institute on Aging R15 (2019-2021).
Press Release: Aging Anole Project awarded a NIH Grant
Beatty AE, CJ Ballen, E Driessen, TS Schwartz , RM Graze. 2021. Addressing the unique qualities of upper-division biology CUREs through the integration of skill-building. Integrative and Comparative Biology. https://doi.org/10.1093/icb/icab006
Beaty, AE, TS Schwartz. 2020 Gene expression of the IGF hormones and IGF binding proteins across time and tissues in a model reptile. Physiological Genomics. https://journals.physiology.org/doi/abs/10.1152/physiolgenomics.00059.2020