Research to Inform the Field of Precision Gerontology

Research projects conducted over 36 months include:
1. Underlying biological mechanisms of psychiatric illness in middle and later life
Many recent studies point to associations between psychiatric illness and age-related disorders such as frailty and dementia. Growing evidence focuses on how abnormalities in biological aging processes impact manifestation and outcomes of older adults living with psychiatric disorders. By focusing on biological pathways that are relevant to both psychiatric disorders and age-related outcomes, our research can identify novel geroscience-guided interventions to prevent or reduce disease burden or incidence of age-related outcomes. Mechanisms of mental disorders are heavily dependent on interactions of multiple etiological factors, which also can affect the aging process and increase risk of worse health outcomes. Our investigation will help inform development of more precise interventions that can mitigate their negative effects in the biology of aging.
2. Underlying causes of sarcopenia in middle and later life
Recent consensus statements on sarcopenia have called for research to better understand why decrease in physical function seen in sarcopenia is outpaced by loss of muscle mass. Decrease in muscle quality has been attributed to numerous physiological changes to muscle adiposity, stiffness, fascicle structure, and neuromuscular changes. Because each of these changes is differentially affected by exercise, dietary, supplemental, and therapeutic interventions utilized, it is important to understand what risk factors affect each component so that interventions can be tailored to treat and prevent loss of muscle function. Accordingly, in this research project we will explore underlying causes of age-related loss of muscle quality to inform development of precision-based interventions that also take into account increased age-related heterogeneity of health.
3. Drug repurposing and target gene discovery for interventions in aging
As aging underlies multiple diseases and conditions, targeting aging may prevent or delay the onset of multiple diseases and conditions based on the geroscience hypothesis. While there is increasing research on drug discovery, no drug has been approved to treat or prevent aging. One hurdle is that aging has not been recognized as a clinical outcome for pharmacological interventions. In contrast, several approved drugs to treat diseases have shown preclinical and clinical evidence for reducing risks of multiple diseases, extending lifespan and healthspan. We propose to use genetic and phenotypic data of UK Biobank to emulate randomized controlled trials to evaluate existing drugs for intervention in aging, or genes associated with hallmarks of biological aging as potential gerotherapeutic targets.