The Problem
The immune system can patrol for and destroy senescent, or aged cells. Senescent cells are drivers of age-related disease and removing them helps remediate aged tissues. It was recently discovered that these cells have an unusually high metabolism.
The Goal
Reduce the metabolism in the senescent cells to see if doing so renders them non-functional. Drugs currently on market have this ability but were developed for an unrelated purpose and were ultimately abandoned. We aim to harness them in the fight against senescence as a new type of senolytic – or drug that kills senescent cells.
The Status
These drugs have been tested as senolytics and have shown to be effective against senescent cells, while leaving healthy cells alone. Dosing levels are being optimized and the strongest candidate for therapy will be tested in a mouse model for IPF.
A New Senolytic Target for Drug Repurposing with Lower Toxicity
The Sharma lab discovered a previously-unknown metabolic abnormality in senescent cells. The deviation from nonsenescent cells was of such magnitude that it could be indispensable to senescent cell survival, such that inhibiting it could be a viable senolytic strategy.
Probing the signaling system underlying this phenomenon identified several potential points of intervention, of which one seemed strongest. Small molecules had previously been developed to modulate a different primary molecular target and with a different intended disease indication yet were known to inhibit a key signaling mechanism regulating the activity of interest. When tested in senescent vs. nonsenescent cells, the Sharma lab demonstrated strongly differential senolytic activity in several cell types induced to senescence by any of several means. They have now begun testing these agents in a mouse model.
Once the dosing regimen for these agents is optimized, the strongest candidate will be tested in a mouse model of idiopathic pulmonary fibrosis (IPF), a disease of aging closely linked to senescent cells.
Team Members
Please visit the Work With Us page to learn about available positions.
Dr. Amit Sharma
Principal Investigator
Dr. Amit Sharma was awarded a Master’s degree in Biomedical Sciences from Delhi University, India. He received his PhD in 2009 in Biotechnology from University of Pune for his work demonstrating microRNA regulation of cytokines involved in allergic inflammation in mice model. Dr. Sharma’s postdoctoral research at the Buck Institute, Novato California involved investigating novel molecular regulatory pathways involved in genotoxic stress and cellular senescence in invertebrate and mammalian models.
Dr. Sharma is the SENS Research Foundation Group Lead in the Senescence Immunology Research Group. His research focus involves studying how aging and senescence affects the immune system and his research group will also investigate strategies to harness the immune system in mitigating deleterious effects of senescent cells with translational focus.
Funding
Annual Budget
200,000 USD
