A research paper published in Aging explored a link between breast cancer, hematopoietic cell transplants (HCTs), an increase in physical frailty, and cellular senescence.
Treatment comes at a cost
HCTs and breast cancer treatment are lifesaving procedures. However, chemotherapy in breast cancer sharply increases p16INK4a, a key biomarker of cellular senescence [1], and HCTs are known to cause accelerated aging [2]. It is unsurprising, then, that people who had undergone such treatments are much more frail than most people, and their physical abilities often resemble those of much older people [3, 4]. As frailty is often accompanied by an increase in mortality, these researchers sought to determine its effects.
This work analyzed its population of 124 former breast cancer and HCT patients by connecting frailty to quality of life, functional assessments, and p16INK4a. Frailty and quality of life were assessed with well-known standardized measurements. People were tested on whether they were constantly exhausted, had unintentionally lost significant weight, walked slowly, could perform only limited physical activity, or had poor grip strength: one or two of these criteria marked someone as being pre-frail, and having least three of these criteria would mark someone as physically frail.
Chronological age was only one factor
About half of the participants were over the age of 60, and slightly over two-fifths were physically frail. While older people were more likely to be frail, the correlation was only moderate: the average age of the frail group was 63, while that of the non-frail group was 56. Frail people were also more likely to have had treatments more recently: an average of 3.4 years compared to 5.8 for the non-frail group. Breast cancer was less heavily correlated with frailty than HCTs were.
There were a few key associations. People who had lost weight, had less grip strength, or less physical ability were more likely to have increased p16INK4a. As expected, people with frailty had significantly reduced quality of life metrics and physical performance. BMI wasn’t significantly correlated with frailty, however.
While this was a relatively small and limited study, and the sample sizes were not very large, it still illustrated the downstream dangers of increasing senescent cell burden. Causing accelerated aging isn’t just accelerating mortality; it also has significant and measurable impacts on how people are able to live. Therefore, replacing harmful-but-necessary treatments with treatments that lack such serious side effects is a research priority.
Literature
[1] Shachar, S. S., Deal, A. M., Reeder-Hayes, K. E., Nyrop, K. A., Mitin, N., Anders, C. K., … & Muss, H. B. (2020). Effects of breast cancer adjuvant chemotherapy regimens on expression of the aging biomarker, p16INK4a. JNCI cancer spectrum, 4(6), pkaa082.
[2] Uziel, O., Lahav, M., Shargian, L., Beery, E., Pasvolsky, O., Rozovski, U., … & Yeshurun, M. (2020). Correction: Premature ageing following allogeneic hematopoietic stem cell transplantation. Bone marrow transplantation, 55(7), 1519.
[3] Ness, K. K., Krull, K. R., Jones, K. E., Mulrooney, D. A., Armstrong, G. T., Green, D. M., … & Hudson, M. M. (2013). Physiologic frailty as a sign of accelerated aging among adult survivors of childhood cancer: a report from the St Jude Lifetime cohort study. Journal of Clinical Oncology, 31(36), 4496-4503.
[4] Arora, M., Sun, C. L., Ness, K. K., Teh, J. B., Wu, J., Francisco, L., … & Bhatia, S. (2016). Physiologic frailty in nonelderly hematopoietic cell transplantation patients: results from the bone marrow transplant survivor study. JAMA oncology, 2(10), 1277-1286.
