Clinical Study Shows Cancer Treatment Speeds Up Biological Aging
Cancer is an age-related disease, and cancer treatment, because of its profound biological stress, could further increase the risk of age-related health problems, including disabling cancer-related symptoms like fatigue.
New research from Emory University indicates accelerated biological aging in adult cancer survivors during and after cancer treatment that is linked to greater fatigue and inflammation. This study, published in the journal Cancer, suggests that inflammation may be a target to reduce the impact of age acceleration on poor functional outcomes.
Biological aging influences health
Research into aging shows that disease and health conditions are closely linked with chronological age. However, why individuals who share the same chronological age have vastly different health outcomes as they get older is a major open question. That’s why researchers are trying to understand other factors that play a part in the aging process that could explain these differences.
Recent studies show that genetics play a major role in aging. Genes change and get activated differently throughout the lifespan. These changes may happen because of the simple passing of time or because of changing environmental conditions. For example, as the body matures and cells divide, specialized structures at the tips of chromosomes become shorter. These structures, known as telomeres, can be used to predict certain health outcomes (1).
More recently, ornamental modifications to DNA called methylation have been used as an “epigenetic clock” to examine the differences between actual chronological age and epigenetic age. This approach has been used to evaluate age acceleration, which occurs when individuals age faster than what is expected for their chronological age (2). Epigenetic age has also been implicated as a predictor for several different health outcomes, including several diseases and chronic conditions like cancers, cardiovascular disease, and neurodegenerative conditions (3,4).
Cancer increases aging through inflammation
A major risk that the aging population faces is cancer. Besides being a significant contributor to mortality in older age, researchers speculate that cancer-related changes may also contribute to the aging process, leading to a sped-up rate of aging (5). This might be due to the disruption that cancer causes in the immune system. Research shows that chronic inflammation becomes an issue in older age.his prolonged state of immune overreaction plays a role in diseases that are common in old age, such as cancer, neurodegenerative disorders, and cardiovascular disease.
This concept has garnered so much attention that scientists have coined the term “inflammaging” to describe this phenomenon. Researchers measure inflammatory responses through the use of special lab tests that measure markers for inflammation. Two of these inflammatory biomarkers are C-reactive protein and interleukin-6. These compounds have been implicated in the development of several age-related diseases (6).
Accelerated aging increases fatigue
Although many of the changes that happen because of inflammation are not immediately visible, scientists believe that the sped-up aging process can increase fatigue. One of the most common side effects of all cancers is fatigue. Head and neck cancer (HNC) patients are especially prone to this side effect. Scientists believe that fatigue could be due to the effects of cancer on their bodies, but also because of the aggressive chemotherapy and radiotherapy used in the treatment of HNC.
HNC patients that experience excessive amounts of fatigue also report having a poor quality of life and lower rates of survival (7). Accelerated aging and fatigue seem to lead to a vicious circle, increasing the effects of each other. These types of symptoms significantly affect the diet and physical capabilities of patients, resulting in faster age acceleration and poorer survival due to other age-related causes (8). Since HNC patients have a diagnosed chronic condition, increased inflammation, and increased levels of fatigue, it makes them an ideal target for research to further understand the accelerated aging process.
Radiation therapy speeds up biological aging in cancer patients
Xiao and colleagues examined the effects of anti-cancer therapies on accelerated aging in HNC patients. The study examined data from 133 patients who had been diagnosed with HNC. Researchers followed these patients for a year and made a note of their symptoms and treatment (9).
The study examined blood samples for inflammatory biomarkers and DNA methylation as a way of assessing age acceleration. Results showed that some treatments increased aging significantly. Half of all the patients experienced severe fatigue as well. Fatigue seemed to be worse immediately after radiotherapy, where aging acceleration was measured at almost 5 years. Patients with the highest levels of fatigue had up to 3.1 years of accelerated aging.
The connection to inflammation was clear, as patients with the highest inflammatory markers had almost 5 years higher accelerated aging than the rest. However, this increase in age acceleration seemed to decrease once treatment was over, and inflammatory markers also decreased. The results also show that combined radiotherapy and chemotherapy had the greatest sped up aging effect, but certain chemotherapy drugs such as cisplatin had a worse effect on aging.
These results show the impact cancer treatments and inflammation can have on cellular aging. Understanding this process will allow researchers to develop treatments that induce less stress on cells and that can avoid speeding up the aging process.
"Our findings add to the body of evidence suggesting that long-term toxicity and possibly increased mortality incurred from anti-cancer treatments for patients with HNC may be related to increased epigenetic aging and its association with inflammation," said lead author Canhua Xiao, PhD, RN, FAAN, of the Emory University School of Nursing, in Atlanta. "Future studies could examine the vulnerabilities that may account for sustained high our findings add to the body of evidence suggesting that long-term toxicity and possibly increased mortality incurred from chemoradiation, fatigue, and inflammation among patients."
- Epel ES, Blackburn EH, Lin J, et al. Accelerated telomere shortening in response to life stress. Proc Natl Acad Sci U S A. 2004;101(49):17312-17315. doi:10.1073/pnas.0407162101
- Horvath S. DNA methylation age of human tissues and cell types [published correction appears in Genome Biol. 2015;16:96]. Genome Biol. 2013;14(10):R115. doi:10.1186/gb-2013-14-10-r115
- Chen BH, Marioni RE, Colicino E, et al. DNA methylation-based measures of biological age: meta-analysis predicting time to death. Aging (Albany NY). 2016;8(9):1844-1865. doi:10.18632/aging.101020
- Salameh Y, Bejaoui Y, El Hajj N. DNA Methylation Biomarkers in Aging and Age-Related Diseases. Front Genet. 2020;11:171. Published 2020 Mar 10. doi:10.3389/fgene.2020.00171
- Guida JL, Ahles TA, Belsky D, et al. Measuring Aging and Identifying Aging Phenotypes in Cancer Survivors. J Natl Cancer Inst. 2019;111(12):1245-1254. doi:10.1093/jnci/djz136
- Bruunsgaard H, Ladelund S, Pedersen AN, Schroll M, Jørgensen T, Pedersen BK. Predicting death from tumour necrosis factor-alpha and interleukin-6 in 80-year-old people. Clin Exp Immunol. 2003;132(1):24-31. doi:10.1046/j.1365-2249.2003.02137.x
- Fang FM, Liu YT, Tang Y, Wang CJ, Ko SF. Quality of life as a survival predictor for patients with advanced head and neck carcinoma treated with radiotherapy. Cancer. 2004;100(2):425-432. doi:10.1002/cncr.20010
- Irwin ML, Smith AW, McTiernan A, et al. Influence of pre- and postdiagnosis physical activity on mortality in breast cancer survivors: the health, eating, activity, and lifestyle study. J Clin Oncol. 2008;26(24):3958-3964. doi:10.1200/JCO.2007.15.9822
- Xiao C, Beitler JJ, Peng G, et al. Epigenetic age acceleration, fatigue, and inflammation in patients undergoing radiation therapy for head and neck cancer: A longitudinal study [published online ahead of print, 2021 May 24]. Cancer. 2021;10.1002/cncr.33641. doi:10.1002/cncr.33641