Premature physiologic aging as a paradigm for understanding increased risk of adverse health across the lifespan of survivors of childhood cancer

Kirsten K. Ness, James L Kirkland, Maria Monica Gramatges, Zhaoming Wang, Mondira Kundu, Kelly McCastlain, Xiujie Li-Harms, Jinghui Zhang, Tamar Tchkonia, Saskia Martine Francesca Pluijm, Gregory T. Armstrong

Research output: Contribution to journalReview article

13 Scopus citations

Abstract

The improvement in survival of childhood cancer observed across the past 50 years has resulted in a growing acknowledgment that simply extending the lifespan of survivors is not enough. It is incumbent on both the cancer research and the clinical care communities to also improve the health span of survivors. It is well established that aging adult survivors of childhood cancer are at increased risk of chronic health conditions, relative to the general population. However, as the first generation of survivors age into their 50s and 60s, it has become increasingly evident that this population is also at risk of early onset of physiologic aging. Geriatric measures have uncovered evidence of reduced strength and speed and increased fatigue, all components of frailty, among survivors with a median age of 33 years, which is similar to adults older than 65 years of age in the general population. Furthermore, frailty in survivors independently increased the risk of morbidity and mortality. Although there has been a paucity of research investigating the underlying biologic mechanisms for advanced physiologic age in survivors, results from geriatric populations suggest five biologically plausible mechanisms that may be potentiated by exposure to cancer therapies: increased cellular senescence, reduced telomere length, epigenetic modifications, somatic mutations, and mitochondrial DNA infidelity. There is now a critical need for research to elucidate the biologic mechanisms of premature aging in survivors of childhood cancer. This research could pave the way for new frontiers in the prevention of these life-changing outcomes.

Original languageEnglish (US)
Pages (from-to)2206-2215
Number of pages10
JournalJournal of Clinical Oncology
Volume36
Issue number21
DOIs
StatePublished - Jul 20 2018

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ness, K. K., Kirkland, J. L., Monica Gramatges, M., Wang, Z., Kundu, M., McCastlain, K., Li-Harms, X., Zhang, J., Tchkonia, T., Francesca Pluijm, S. M., & Armstrong, G. T. (2018). Premature physiologic aging as a paradigm for understanding increased risk of adverse health across the lifespan of survivors of childhood cancer. Journal of Clinical Oncology, 36(21), 2206-2215. https://doi.org/10.1200/JCO.2017.76.7467