Danica Chen

Associate Professor

Department of Nutritional Sciences and Toxicology
University of California, Berkeley

One of the most fundamental questions in biology is how we age. The past decades have witnessed a significant revision of a traditional view that aging is simply a random and passive process that is solely driven by entropy. In fact, the aging process is regulated genetically and lifespan can be extended by single gene mutations. Intriguingly, emerging evidence suggests that many aging-associated cellular processes can even be reversed. Our research aims to understand signal transduction that regulates the aging process and explore therapeutic targets to slow or even reverse aging. The most intriguing aspect of pharmaceutical intervention that targets the aging pathways is that, instead of targeting a specific disease, it has the potential of ameliorating a wide array of seemingly unrelated diseases associated with aging, such as cancer, tissue degeneration, metabolic syndrome and immune dysfunction.

Aging is a multifaceted degenerative process that eventually leads to tissue function decline. These observations suggest that stem cells are likely to play a pivotal role in aging, because tissue maintenance throughout adult life depends on the integrity of stem cells. The ability of stem cells to self-renew and repair damaged tissues decreases with age, which may underlie much of the aging-associated degeneration in mammals. By understanding the molecular basis of stem cell maintenance and aging, we gain insights into how tissues maintain their regenerative potential and how derailed stem cell function leads to degenerative diseases. Our recent studies show that ROS, a cause of stem cell aging, increase with age through a regulated process, with SIRT3 playing a role. In contrast to the previous thought that ROS cause aging due to the passive accumulation of oxidative damage over the lifetime, our studies suggest that the effects of ROS on stem cell aging is likely acute and reversible. We have also discovered a mitochondrial UPR-mediated metabolic checkpoint that regulates stem cell maintenance and implicate mitochondrial protein folding stress as a trigger of stem cell aging. Our future studies will reveal novel mechanisms regulating stem cell aging and develop therapeutic approaches to treat tissue degeneration.