Junior faculty project investigates aging from multiple perspectives

Benjamin Franklin once famously wrote that “...in this world nothing is certain but death and taxes.” Franklin neglected to add another inescapable reality of life: aging.

Like it or not, as we grow older our muscles weaken, our skin wrinkles, our wounds take longer to heal, and our immune systems become less robust, to cite just a few of the inevitabilities of growing older. In fact, aging gradually affects virtually every tissue and organ in the body.

So-called adult stem cells, which reside in many organs, regenerate tissue throughout our lives. But they, too, start to age with time and their regenerative capacity diminishes, leading scientists to postulate that stem cells play a central role in the aging process. Indeed, evidence now indicates that the progressive decline in stem cell number and function with age contributes significantly to conditions associated with aging.

But what drives stem cell aging? Finding answers to this complex and largely unexplored question will provide novel insights into the normal aging process and many conditions that afflict the elderly, and could eventually lead to new, targeted treatments for this large and rapidly growing segment of the population.

Exploring the “Epigenetics of Stem Cell Function and Aging” is the mission of a Junior Faculty Program project funded by HSCI in 2009. Launched in 2007, HSCI’s Junior Faculty Program provides collaborative teams of Harvard-affiliated junior faculty engaged in stem cell research with three years of significant funding and access to HSCI’s many resources.

Led by HSCI principal faculty member Alex Meissner, PhD, of the Broad Institute and Harvard’s Department of Stem Cell and Regenerative Biology, this Junior Faculty project also includes Andrew Brack, PhD, and Caroline Burns, PhD, of Massachusetts General Hospital; Benjamin Ebert, MD, of Brigham and Women’s Hospital; and Derrick Rossi, MD, of the Immune Disease Institute, all of whom banded together to study the role of the epigenome on aging from different perspectives.The epigenome provides critical instructions to cells that modify their behavior without altering the DNA sequence, or genome, within the cells. Epigenetic mechanisms play essential roles in development, directing cell fate, and diseases such as cancer.

Meissner’s HSCI-funded research is focusing on the mechanisms of epigenetic regulation of pluripotent stem cells (cells that can become any tissue type in the body). Brack is exploring the epigenetic regulation of muscle stem cells during aging, while Burns is looking at the role of epigenetics in the heart’s ability to repair itself as it ages. Ebert and Rossi are investigating different aspects of epigenetics and its impact on the blood: Ebert is focusing on a blood disease, myelodysplastic syndrome (MDS), that primarily affects the elderly; while Rossi is working on understanding the epigenetic regulation of the aging of hematopoietic (blood-forming) stem cells. To keep abreast of each other’s work and explore further opportunities for collaboration, the group meets informally at least every other month.

As it enters its third and final year of funding, Meissner says that the Junior Faculty group has made considerable progress. “On all fronts, our work is moving along quite nicely,” he said.

For instance, both he and Rossi are currently preparing manuscripts based on this project that will be submitted to major scientific journals this summer. The group has also formed new collaborations among its members and with a scientist, Elaine Fuchs, PhD, at the Rockefeller University, whose research focuses on the skin.

In addition, the project has enabled several of its members to gather strong preliminary data to apply for larger, longer-term funding from federal agencies like the National Institutes of Health and other funding sources.

“Three years is a short time frame for research, but this grant gave us a jump-start that sped things up considerably,” said Meissner. “There’s no question that we wouldn’t have gotten funding for this research from traditional sources. And without the collaboration that characterizes our Junior Faculty project, it would have taken another five years to reach where we are now.”