Why does cancer risk increase exponentially with age? Is there a molecular signature of aging and cancer? What are the age-dependent targets in cancer? The Haigis lab has been studying the genetics of human cancer from young or aged individuals to identify signatures that are age-dependent and causal for cancer risk. We have generated novel mouse models to induce lung cancer in young and aged Cas9 mice, which provide a powerful new tool to answer these questions (Haigis lab, manuscript in revision).
Legend: GFP-labeled lung tumors induced in young or aged Cas9 mice. Aged mice demonstrate larger and more aggressive tumor growth (Haigis Lab, unpublished).
The Haigis Lab has provided new insights to demonstrate that metabolism contributes to declining immune functions with aging. Experiments with T cells from young or old animals show that one carbon metabolism, which is important for redox control and nucleotide synthesis, is repressed in aged T cells (PMCID: PMC6310842). Furthermore, we have discovered that declining immune functions contribute to increased cancer risk with aging, in part, due to a loss in the ability of T cells to recognize tumor antigens (PMCID: PMC11532741).
Legend: Electron Microscopy of mitochondria from aged T cells shows disorganized cristae morphology (Haigis lab, unpublished).
Marcia C. Haigis is a Professor of Cell Biology at Harvard Medical School, Co-Director of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School, and Co-Director of the Bertarelli Rare Cancers Initiative. She is an active member of the Ludwig Center at Harvard, the Gene Lay Institute, and affiliated with the Broad Institute. Dr. Haigis obtained her Ph.D. in Biochemistry from the University of Wisconsin and performed postdoctoral studies at MIT studying mitochondrial metabolism. Dr. Haigis has made fundamental contributions to our understanding of how mitochondria contribute to human health, aging, and diseases of aging. Her pioneering studies identified ways that mitochondria utilize fuels and signal in to support cell proliferation, pivotal in immune cell activation. Most recently, her work has transformed our understanding of how aging, diet, and obesity contribute to tumorigenesis and diminish anti-tumor immunity. Dr. Haigis is the recipient of numerous honors and awards, including the Brookdale Leadership in Aging Award, the Ellison Medical Foundation New Scholar Award, the American Cancer Society Research Scholar Award, the National Academy of Medicine Emerging Leaders in Health and Medicine Program. She is the recipient of the 2023 Samsung Ho-Am Prize in Medicine. Dr. Haigis was elected to the National Academy of Medicine in 2024. Dr. Haigis serves on numerous academic and for-profit scientific advisory boards.