Mycobacterium tuberculosis causes TB in human lungs by triggering aberrant immunological responses that lead to tissue damage eroding lung tissue and enabling the pathogen to spread to other humans by coughing. We have discovered that a key element of this aberrant immune response is that the pathogen triggers immune cells to enter into a senescent state (as is seen in human aging) whereby immune cells lose the ability to respond correctly to the infectious challenge. We propose to use advanced molecular and pharmacologic tools to probe the details of this aberrant senescence response, and then to test novel small-molecule senolytic agents in animal models to see if they have the potential to serve as novel TB drugs.