The goal of our work is to understand the molecular mechanisms governing aging and longevity, including diseases that accompany old age.
As humans age, we experience many forms of physiological decline. We used to think that aging was an unavoidable result of living, simply a matter of cells wearing out over time. However, genetic studies in several model organisms have demonstrated convincingly that this is not the case. In worms, flies, yeast, and mice, single gene mutations have resulted in dramatic increases in lifespan. What this suggests is not only that aging is a regulated process, but also that it can be disrupted. Mutations in regulatory genes, such as the insulin receptor, increase longevity. Thus, some downstream genes must normally cause the animal to age, while other genes seem to be capable of preventing aging.
Currently, longevity studies in model organisms commonly focus on the ultimate endpoint, death. To change this paradigm, my lab focuses on genetic pathways and specific biological functions that become impaired with age.
To find genes that contribute to maintaining the biological processes that exhibit age-related decline, we use the small model organism, the nematode C. elegans. This worm shares several aging traits with humans: it slows down with age, its skin becomes wrinkled, and its ability to sense its environment declines. These worms have an experimentally feasible lifespan (2-3 weeks) and their signs of aging are visible at both the gross and microscopic level, so we can measure the changes that take place over time rapidly.
Because C. elegans shares many aging traits with humans, we can use it to probe the vital biological processes that otherwise degrade with age.
For example, various activities are easily measured in C. elegans, and we can assess these behaviors with age. By designing quantitative methods to assess function and then performing tests to look for improvement, we can find the genes required for maintenance of these functions.
We also use expression microarrays to analyze changes in transcription that occur with age and in mutant backgrounds that delay aging. This work has already identified novel pro- and anti-aging genes, and will further elucidate the molecular mechanisms underlying age-related disease. The development of therapeutics to affect these aging-related genes will drastically improve quality of life in the elderly and help in the treatment of age-related diseases. By using a model system with a short lifespan, measurable behaviors, and simple genetics, we should be able to identify quickly genes that are critical for the maintenance of health.
- National Institutes of Health Director's New Innovator Award (2008)
- Pew Charitable Trusts Pew Scholars in the Biomedical Sciences
- Alfred P. Sloan Foundation Research Fellows Program
- New Jersey Commission on Cancer Research (NJCCR)
- March of Dimes Basil O'Connor award
- The McKnight Endowment Fund for Neuroscience
- W.M. Keck Foundation Distinguished Young Scholar Award
- American Federation for Aging Research
- National Science Foundation