Understanding the effects of chemotherapy on molecular aging.

Impact

While often curative, chemotherapy also has unwanted side effects that endure after treatment has ended, including biological aging. Dr. Muss and his research team are conducting a series of studies to understand the effects of chemotherapy on aging of the immune system and identifying strategies to prevent or attenuate these unwanted side effects and improve the quality of life of patients who have undergone this treatment.

Progress Thus Far

Dr. Muss’ team has shown that different adjuvant chemotherapy regimens affect a marker of aging called p16 in both older and younger women with breast cancer and that chemotherapy rapidly and irreversibly age their immune systems by about ten years. He has also found that p16 can be used to predict which patients receiving chemotherapy are more likely to experience side effects such as fatigue and chemotherapy-induced peripheral neuropathy. Levels of p16 increase dramatically and rapidly with chemotherapy in a large percentage of patients and being able to identify those patients who are likely to have accelerated aging will enable development of personalized interventions.  

What's next

Dr. Muss is now focusing on p16 and its relationship to other toxicities such as cardiovascular disease in long-term survivors. He and his team are conducting a trial in patients who received adjuvant (post-surgery) chemotherapy to compare changes in p16 levels with other molecular changes that occur with age, for example changes in DNA function, and to correlate p16 with long-term outcomes during survivorship. Dr. Muss hopes to uncover the long-term implications of chemotherapy-accelerated biologic aging (e.g., heart disease, diabetes, second cancers). Dr. Muss is now testing the efficacy of drugs called senolytics and strength training exercises in slowing the effects of chemotherapy-associated aging.