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Aging Biology and Health Disparities Research: Team Science for Pathways to Discovery

Carl V. Hill
Carl V. HILL,
Director, Office of Special Populations,
Office of the Director (OD)
.

On July 8, 2015, NIA’s Office of Special Populations released PA-15-293, “Aging Research to Address Health Disparities.“ It seeks to support aging research that addresses disparities in health, including preclinical, clinical, social, and behavioral studies.

A few weeks ago, I sat down with Dr. Felipe Sierra, director of the Division of Aging Biology (DAB) to discuss some opportunities for involving basic researchers in health disparities research.

Q. What health-related processes and outcomes are most relevant for aging biology researchers interested in investigating health disparities?

A. Because DAB’s research portfolio focuses on molecular and cellular mechanisms of aging, and most – though not all – of our work is done in animal models, historically it’s been a struggle for our researchers to get involved in health disparities research. But, things are changing, as health disparities research moves from being primarily descriptive to a search for mechanisms that include the underlying biological basis of health differences.

I think there’s a huge opportunity for collaboration. Basic researchers should be involved as co-investigators in grant proposals that address biological variability. This is important because, just as basic biologists don’t always understand the complexities and underlying assumptions in behavioral and disparities research, behavioral researchers don’t always have a full grasp of the most relevant and reliable biological measurements or how the data are analyzed and presented from the perspective of a basic biologist.

One area of health disparities in which basic biologists can and should take the lead is in gender differences. We see this over and over again in DAB’s Interventions Testing Program. With many of the life-extension drugs tested, we’ve seen remarkable and reproducible gender differences, but not always in the same direction. Some drugs work only in males, while others only in females. There’s a huge knowledge gap there. Most biomedical research is done in male C57Bl6 mice, and once a finding is made, we tend to generalize and say something occurs “in mice,” when we really don’t know if this is true. Is it true in both males and females? In both young and old mice? In mice of different strains? Under different housing conditions? We don’t really know!

Q. What biological, behavioral, or social factors should aging biology researchers consider when examining pathways that sustain health disparities? 

A. Many behavioral and social factors are difficult to model in animals, with some exceptions in non-human primates, rodents, and dogs. Nevertheless, behavioral research has developed some successful interventions, and studying the biological basis of behavior has been fruitful in some cases.

For example, we’ve known for many years that one behavior, caloric restriction, increases lifespan in many—though not all—species tested. This is a behavioral paradigm that is difficult to apply to people, yet basic biologists have been able to take advantage of it to glean new information about molecular pathways important for caloric restriction’s effect on longevity and healthspan. As a result, the role of pathways such as mTOR, AMPK, IGF1 and sirtuins, which were independently identified through genetic studies, were confirmed in the caloric restriction model. A similar approach could be useful when applied to some of the other behavioral interventions identified as having a positive effect on healthspan.

Another possible area for collaboration is on the most currently measured parameters used in cohort human studies, such as telomere length and levels of some pro-inflammatory markers, including IL6 and CRP. These are extremely crude and their causative role in age-related diseases and conditions is questionable, but they are what is available for large-scale studies in people. I think greater collaboration with basic aging biology researchers can provide useful knowledge and guidance in expanding and refining the scope of these measures, identifying key pathways, and showing potential targets for intervention.

Q. How can aging biology researchers get involved with health disparities research right away?

A. Again, the obvious place is as collaborators in multidisciplinary teams, where their expertise should be sought if the biological basis of behavioral and health disparities is being explored. Areas such as genetics, epigenetics, chronic inflammation, proteostasis, and stress control in  health disparities can be addressed if the teams include sufficient expertise in basic biology. This administrative supplement, “Aging Research to Address Health Disparities,” is a great opportunity for aging biology researchers to consider ideas for health disparities research.

Q. What research papers would you suggest teams of interdisciplinary investigators review if they’re interested in including biological factors in their research on health disparities?

A. That’s not an easy question, because the field of aging biology is exploding and a week rarely passes without major advances being published in top-tier journals. Two recent review papers cover the most salient aspects of aging biology and geroscience, including the work by Lopez-Otin (Cell, June 2013), as well as the work of our own GeroScience Interest Group (Kennedy, et al., Cell, Nov 2014).

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Thanks to Dr. Sierra for his insights in this area. Do you have ideas on how aging biology researchers can participate in health disparities research? We’d love to hear them, so feel free to comment below.

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