Updated March 1, 2019

TPLH and collaborators at SNPRC, UTHSCSA, and Wake Forest Health received a National Institute on Aging U19, one of the largest grants given by NIA.

In September 2018, TPLH received the encouraging news of a successful U19 award from the National Institute on Aging (NIA). The U19 grant mechanism is one of the largest provided by NIH and provides over $14,000,000 support over the next five years for studies of developmental programming-aging interactions in the baboon. The project is a collaboration between TPLH, the Southwest National Primate Research Center (SNPRC), the University of Texas Health Science Center San Antonio (UTHSCSA), and Wake Forest Health. Developmental programming is the concept that challenges during critical developmental time windows have lifelong effects on health. In particular, we study how maternal undernutrition and maternal obesity during pregnancy and lactation affect offspring development, health, and aging for the rest of their lives. We will also evaluate the effects of stress hormones on aging.

The U19 consists of three projects about programming-aging interactions: 1) Hypothalamic-hippocampal-pituitary-adrenal axis (HHPAA) function in relation to the brain and behavior; 2) Cardiovascular function; and 3) Metabolism of the liver, fat, and skeletal muscle. In each of these areas, we investigate the effects of maternal undernutrition and obesity on their adult offspring as they age. To be able to study aging of these functions, we also will determine normal structure and function in control animals at ages across the life-course from human equivalent 18 years of age to 68. We further study the aging process by analyzing the effects of different levels of cortisol, an important orchestrator of both programming and aging.

The three projects involve a wide variety of approaches. We conduct in vivo magnetic resonance imaging (MRI) of heart function as well as aging of the brain. We are very interested in 24-hour rhythms and cutting-edge cognitive testing. In addition, we use microscopical and cell culture approaches. We continue the in-depth study of genes and cell signaling that we have published in both the baboon (PMID 29516496) and the rat (PMID 29972240). Cognitive testing is conducted on a touchscreen computer using the state-of-the-art Cambridge Neuropsychological Test Automated Battery (CANTAB), shown in the figure below. MRI is performed at the UT Health Research Imaging Institute.

This research is essential for improving human health span. It is now clear that developmental programming can influence health over the whole life-course. There are no other similar longitudinal studies in this very important area in any other Centers. Because of the unique nature of this program we interact and share resources with other investigators in 10 countries worldwide. Our overall aim is to achieve a detailed understanding of the mechanisms of programming-aging interactions and construct a complete phenotype across the life course.

Baboon using a touchscreen computer for CANTAB cognitive testing.