Adjuvant chemotherapy increases markers of molecular aging in the blood of BC survivors

March 28, 2014

Adjuvant chemotherapy for breast cancer is "gerontogenic", accelerating the pace of physiologic aging, according to a new study published March 28 in the Journal of the National Cancer Institute.

Loss of organ function, characterized by an increase in cellular senescence, is one physiological part of aging. Studies have identified leukocyte telomere length, expression of senescence-associated cytokines including interleukin-6, and expression of p16INK4aand ARF in peripheral blood T lymphocytes (PBTLs) as markers of cellular senescence. The authors previously showed p16INK4a is a marker of accelerated molecular age in PBTLs associated with smoking, physical inactivity, and chronic human immunodeficiency virus infection. To date, the long term effect of cytotoxic chemotherapy given with curative intent on molecular aging has not been reported.

Hanna K. Sanoff, M.D., Norman E. Sharpless, M.D., and Hyman B. Muss, M.D., and their colleagues prospectively collected blood and clinical data from 33 women with stage I-III before, immediately after, 3 months after, and 12 months after anthracycline-based chemotherapy. Blood was analyzed for markers of cellular senescence. They observed increased expression of the senescence markers p16INK4a and ARF in PBLTs immediately after chemotherapy, and which remained elevated for at least a year after treatment. In an independent cohort of 176 breast cancer survivors, prior chemotherapy was associated with a persistent increase in p16INK4a at an average of 3.4y after treatment. These results suggest the age-promoting effects of chemotherapy last for several years after treatment, and may be permanent.

The authors conclude, "We have shown that potently induces the expression of markers of in the hematologic compartment in vivo, comparable with the effects of 10 to 15 years of chronologic aging in independent cohorts of healthy donors." Further studies are underway.

Explore further: Scientists use luminescent mice to track cancer and aging in real-time

Related Stories

Tipping the balance between senescence and proliferation

November 15, 2013

An arrest in cell proliferation, also referred to as cellular senescence, occurs as a natural result of aging and in response to cellular stress. Senescent cells accumulate with age and are associated with many aging phenotypes, ...

Leukemia: Mode of action of a targeted treatment clarified

January 15, 2014

The mechanism of senescence – or premature cell ageing – can have an anticancer effect. This new work, conducted by Hugues de Thé and his team (Paris Diderot University/ Inserm/ CNRS/ AP-HP), was published in Nature ...

Recommended for you

Combination therapy can prevent cytostatic resistance

November 26, 2015

Researchers at Karolinska Institutet have found a new way of preventing resistance to cytostatics used in the treatment of cancers such as medulloblastoma, the most common form of malignant brain tumour in children. The promising ...

Forecasting the path of breast cancer in a patient

November 23, 2015

USC researchers have developed a mathematical model to forecast metastatic breast cancer survival rates using techniques usually reserved for weather prediction, financial forecasting and surfing the Web.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.