C. elegans aging
We are using
the nematode C. elegans as a model system for aging, because it has a rapid
lifespan, a small size, a powerful genetic toolkit and many mutants are already
known to lengthen lifespan. Our approach is to first identify genes that are differentially
expressed in old versus young animals, and then to dissect apart how changes in
these genes lead to functional decline and senescence in old age.
We are studying aging of the human kidney, which begins to show functional decline around age 40. Kidneys age at different rates, such that some people show little or no effects of aging whereas others show rapid functional decline of the kidney.
We have developed a gene expression signature that can be used as an epigenetic clock for normal kidney aging. A major factor responsible for kidney aging is chronic inflammation. At least three pro-inflammatory signaling pathways lead to activation of transcriptional cascades in old age.
Aging and disease are closely related as aging is the largest risk factor for disease, and age-related disease is the primary factor limiting lifespan in modern society. If we could understand the underlying basis for aging, we could reduce the risk of getting these diseases. One potential area for a breakthrough is studying the genetics of people that live to extreme old age, such as centenarians and supercentenarians. Centenarians often showamazing robustness for their age – many are exceptionally alert, active and healthy. Supercentenarians (110 years or older) are the world’s oldest people. Seventy four are alive worldwide, with twenty two in the United States.
We are using full genome sequencing and genome-wide association studies to find genetic loci associated with extreme longevity.