Hyman B. Muss, MD

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. Cellular senescence (CS) has an essential role in aging as an indicator and a cause of aging-related functional decline. Senescent cells cannot divide but secrete factors that promote inflammation and induce senescence in healthy cells locally and at distant sites. 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 and his team have shown that different chemotherapy regimens induce CS and affect a marker of CS called p16 in both older and younger women with breast cancer. They have also observed that chemotherapy rapidly and irreversibly ages their immune systems by about ten years. The team 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. They recently completed a natural aging clinical trial of 250 adults aged 25 to 85 without cancer. The study confirmed results observed in the laboratory and showed that p16 rises quickly with age until about 60, then more slowly, and that higher levels are linked with poorer quality of life. In related work, the team looked at the effect of radiation therapy on fatigue and found that while it did not worsen fatigue in the general breast cancer population, patients from more socially vulnerable communities reported more severe symptoms.

What’s next

Dr. Muss and his team will focus on deepening their understanding of how chemotherapy accelerates aging and identifying patients most at risk for long-term side effects. The team is already halfway through a study of women with early breast cancer that compares those who receive chemotherapy to those who do not. By analyzing blood samples before and after treatment, they will measure p16 levels alongside broad protein patterns to see if chemotherapy increases signs of premature biological aging. This may help predict who is at greatest risk for lasting problems like heart or nerve damage. Dr. Muss and team will also publish findings on the completed trial that tracked p16 levels and patient health several years after treatment, including effects on memory and thinking. Additional studies will test whether DNA circulating in blood can reveal organ-specific aging and how this connects with p16 and protein data.