Factors in the bloodstream can reverse certain characteristics of aging. Studies in the Wagers Lab have uncovered novel and conserved mechanisms and signaling proteins that are present normally in the bloodstream and can reverse some effects of aging in the skeletal muscle, heart and nervous system
This work supports the notion that common signals may control the manifestation of aging effects across the body’s organs and raise the possibility of developing new therapeutic strategies based on blood-borne geroprotective factors that could benefit multiple age-associated diseases that previously have been studied (and treated) as unrelated pathologies.
Legend: Soluble factors and cells found in the blood-stream of young animals can improve certain tissue functions when transferred into aged animals. Images show poor repair of muscle injury in aged mice (left) compared to more robust regeneration of injured muscle tissue after exposure to blood-borne factors from young animals. Identification of the factors present in young and old mice that mediate these responses holds promise for promoting healthy muscle function throughout the lifespan.
Novel systems enabling rapid interrogation of aging regulators and gene-based therapies for aging-related disease. To accelerate the discovery of critical genes and pathways that regulate aging and longevity and of new treatment approaches that can extend healthy lifespan, the Wagers lab has developed powerful platform technologies based on adeno-associated virus (AAV)-mediated delivery of geroprotective genes and sequence-specific (“designer”) genome editing enzymes into endogenous stem cells and tissues of young, aged and progeroid animals
These systems offer new opportunities to rapidly interrogate aging pathways in vivo to uncover novel molecular targets that specifically influence stem cell aging and regenerative function, and to intervene in aging pathologies by delivery of currently “undruggable” therapeutic gene products.
Legend: Robust AAV-mediated gene delivery to cardiac muscle (left) and skeletal muscle (right).
Dr. Amy Wagers is the Forst Family Professor and Chair of Harvard’s Department of Stem Cell and Regenerative Biology. She is also a Senior Investigator in the Section on Islet Cell and Regenerative Biology at the Joslin Diabetes Center, and an active member of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School. Wagers’ laboratory investigates how changes in stem cell activity impact tissue homeostasis and repair throughout life and how stem cells may be harnessed for regenerative medicine using cell transplantation, gene therapy and gene editing approaches. Her recent discoveries regarding the reversibility of aging phenotypes in tissue stem cells and differentiated cells and the feasibility of modifying endogenous stem cell genomes for regenerative medicine have been recognized by numerous awards, including an NIH Pioneer Award, the Vincent Cristofalo ‘Rising Star’ Award, NIA’s Nathan Shock Award, and the NYSCF-Robertson Stem Cell Prize for Significant Achievement in Translational Research.