New research project: Retrolytics – Cells with active retrobiome as a rejuventation treatment

Nearly half of the mammalian genome is comprised of a “retrobiome” including millions of copies of including long and short interspersed virus-like repetitive elements (LINEs). Aging-related failure of silencing mechanisms can result in LINE activation and such LINE active cells –characterized by an expression of interferon (IFN) – may be a mayor contributor to systemic aging. However, the relationship between LINE activation and aging is still extremely poorly understood.

Our specific aims are: (1) to create an “atlas” of IFN expression (tissue localization, cell type) in tissues of wild type mice of different ages under normal and aging-accelerating conditions (total body irradiation, obesity), in mice with short life spans and genetically desilenced retrobiomes (Sirt6- and p53-deficiency), during spontaneous carcinogenesis (mice genetically predisposed to breast and prostate cancer) and under rejuvenation treatments (e.g., rapamycin, senolytic compounds); and (2) to determine the rejuventation effect of pharmacological eradication of IFN-positive cells in the context of normal and accelerated aging and in mice genetically predisposed to premature aging and spontaneous cancer development.

Successful completion of these aims will provide insight into the role of retrobiome-mediated IFN response activation as a regulator of aging and provide proof-of-concept for a new rejuvenation approach, “retrolytic” therapy, based on eradication of cells with retrobiome and IFN response activation.