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

March 28, 2014, Oxford University Press USA

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: Tipping the balance between senescence and proliferation

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, ...

EORTC Cancer in the Elderly Task Force investigates appropriate treatment for elderly patients

November 25, 2013
As we age, we experience a progressive decline in many of our bodily functions. This decline can vary greatly from individual to individual. One 75 year old might still be very active and participate in strenuous physical ...

Imprint of chemotherapy linked to inflammation in breast cancer survivors

March 4, 2014
Many breast cancer survivors experience fatigue and other debilitating symptoms that persist months to years after their course of treatment has ended.

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 ...

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

January 17, 2013
In a study published in the January 18 issue of Cell, researchers from the University of North Carolina Lineberger Comprehensive Cancer Center have developed a new method to visualize aging and tumor growth in mice using ...

Recommended for you

Researchers artificially generate immune cells integral to creating cancer vaccines

August 14, 2018
For the first time, Mount Sinai researchers have identified a way to make large numbers of immune cells that can help prevent cancer reoccurrence, according to a study published in August in Cell Reports.

Chemicals found in vegetables prevent colon cancer in mice

August 14, 2018
Chemicals produced by vegetables such as kale, cabbage and broccoli could help to maintain a healthy gut and prevent colon cancer, a new study from the Francis Crick Institute shows.

Lymphatic vessels unexpectedly promote the spread of cancer metastases

August 14, 2018
Lymphatic vessels actively contribute to the spread of cancer metastases from various organs. This unexpected realisation is the result of a joint study by researchers from ETH Zurich and the University Hospital Zurich as ...

Ovarian cancer genetics unravelled

August 14, 2018
Patterns of genetic mutation in ovarian cancer are helping make sense of the disease, and could be used to personalise treatment in future.

Researchers uncover a major new vulnerability of childhood leukemia

August 14, 2018
Childhood leukemia is a diagnosis that no family ever wants to endure. While the treatment of most types of leukemia has improved steadily over the years, a few specific types remain very difficult to treat. One of these ...

Stress hormone is key factor in failure of immune system to prevent leukemia

August 14, 2018
The human stress hormone cortisol has been identified by scientists at the University of Kent as a key factor when the immune system fails to prevent leukemia taking hold.

0 comments

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.