What inspired you to pursue aging research?
My introduction to science and medicine coincided with the multiple family members experiencing age-related declines. I was struck by how little was known about the mechanism underlying the changes they experienced and how treatment focused on palliating symptoms rather than addressing the systemic root causes. This inspired me to pursue research to shed light on the biologic processes underlying aging with the goal to develop biologically-guided interventions to assist others dealing with age-related disease.
In your view, what does AFAR mean to the field, and what does it mean, for you, to receive an AFAR grant now?
While many funders focus on disease or organ system specific research, the existence of AFAR emphasizes the importance of understanding the biology and consequences of systemic aging as a root cause of morbidity. As an early career researcher beginning my independent lab, this grant allows me to build my research program with a focus on my interest in the biology of aging, rather than shifting towards disease specific research to fit the interests of other available sources. This grant will allow me to build foundational tools for continuing my research even after the grant period has ended.
What is exciting about your research’s potential impact?
While many metrics of “biological age” have been proposed, few have clear functional links to the aging process or provide targets for intervention. Accumulation of mutations in the mitochondrial genome has long been recognized to occur in aging. These events have a theoretical strong mechanistic link to age-related functional change and are thus an appealing potential metric of aging. However, the specific mutations present and their functional relevance have been difficult to assess due to technological limitations. My research program harnesses cutting edge genomic technology to overcome these limitations, opening the door to use of these events as a biologic metric of aging and to develop targeted therapy to offset their impact.
How would you describe your research to a non-scientist?
While all people age, some experience age-related functional change and disease earlier than others. Even within an individual, different organ systems may change at different rates. There is thus a need for a quantitative metric of a tissue’s “biological age,” independent of numeric age, and to develop interventions targeted towards the factors which impact this measure. Cells have organelles called mitochondria which are responsible for energy production. Mitochondria have their own DNA. This DNA is very susceptible to mutations, particularly large deletions. As people age, their cells accumulate mitochondrial DNA with large deletions, which are hypothesized to cause functional changes in cells. The number of mutated mitochondrial DNAs in a tissue may be a useful metric of the biological age, however it has been hard to evaluate this potential as methods for identifying and quantifying these events are limited. We developed two new approaches for characterizing these events which allow increased insight into the location and frequency of specific mutations. I am using these approaches to understand the utility of mitochondrial DNA deletions as metrics of aging in different tissues and cell types so they can be used to quantify aging in future human studies. Further, the deleted mitochondrial DNAs may provide a target for anti-aging therapy, but it has been challenging to pursue this without understanding the functional impact of these events. Our newfound ability to detect these events in more kinds of data sets allows me to identify the relationship between mitochondrial DNA mutations and a cell’s gene expression, giving new insight into their consequences.
