Frailty in childhood cancer survivors
Open accessAbstract
Young adult childhood cancer survivors are at an increased risk of frailty, a physiologic phenotype typically found among older adults. This phenotype is associated with new‐onset chronic health conditions and mortality among both older adults and childhood cancer survivors. Mounting evidence suggests that poor fitness, muscular weakness, and cognitive decline are common among adults treated for childhood malignancies, and that risk factors for these outcomes are not limited to those treated with cranial radiation. Although the pathobiology of this phenotype is not known, early cellular senescence, sterile inflammation, and mitochondrial dysfunction in response to initial cancer or treatment‐related insults are hypothesized to play a role. To the authors' knowledge, interventions to prevent or remediate frailty among childhood cancer survivors have not been tested to date. Pharmaceutical, nutraceutical, and lifestyle interventions have demonstrated some promise. Cancer 2015;121:1540–1547. © 2014 American Cancer Society.
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Aging processes can be accentuated at etiologic sites of multiple acute and chronic diseases, including in children.
“Aging progresses throughout the lifespan can be accentuated at etiologic sites of multiple acute and chronic diseases, including in children6,8–12.”
From Cellular senescence and senolytics: the path to the clinic (2022) · cites this paper as [9]
The Frailty section (page unavailable) says that age-related functional decline can accelerate after acute illness or injury, especially when organ systems are damaged. Potential biological markers of frail health (page unavailable) describes vulnerability in organs exposed to cancer-treatment toxins in children. The paper does not establish the broader claim that aging is accentuated at etiologic sites of multiple acute and chronic diseases generally, including in children outside the childhood-cancer context. (LLM, conf=0.83)
Experimental — accuracy not yet measuredTIS is believed to be a major driving force of frailty and other AEs in adults owing to its detrimental effect on tissue function via chronic inflammation, similar to 'inflammaging'.
“As in children and adolescents, TIS is also believed to be a major driving force of frailty and other AEs in adults owing to its detrimental effect on tissue function via chronic inflammation, similar to 'inflammaging' , which is a chronic mild inflammatory process that develops with age 198,200,201 .”
From Senescence and cancer — role and therapeutic opportunities (2022) · cites this paper as [198]
In “Potential biological markers of frail health” (page unavailable), the paper links cellular senescence to chronic inflammation and hypothesizes that this process contributes to frailty in aging childhood cancer survivors. It does not establish therapy-induced senescence as a major driving force of frailty and other adverse events in adults generally, or explicitly equate the process with inflammaging. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSurvivors of childhood cancers tend to develop chronic conditions such as cardiovascular dysfunction, ischaemic cardiac failure, renal and hepatic disorders, diabetes, poor fitness, muscular weakness and cognitive decline two decades earlier than individuals with no history of paediatric cancer treatment.
“Examples of such accelerated ageing pheno types have been observed in survivors of childhood cancers who are cured from their malignant diseases but tend to develop chronic conditions - such as cardiovascular dysfunction, ischaemic cardiac failure, renal and hepatic disorders, diabetes, poor fitness, muscular weakness and cognitive decline - two decades earlier than individuals with no history of”
From Senescence and cancer — role and therapeutic opportunities (2022) · cites this paper as [198]
The Abstract (page unavailable) says chronic disease rates in survivors in their twenties resemble rates in siblings in their fifties, and that cognitive dysfunction, reduced strength and poor exercise tolerance appear decades early. The Potential biological markers section (page unavailable) also reports increased diabetes risk and coronary artery disease. The copy does not substantiate renal or hepatic disorders or ischaemic cardiac failure, and it does not establish that every listed condition develops specifically two decades earlier. (LLM, conf=0.88)
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References 95 · Cited by 188
Research works printed but not linked: 1
- [91]Buchner DM Wagner EH Preventing frail health. Clin Geriatr Med 1992 8 1 17 1576567
- Authors
- Ness, K. K., Armstrong, G. T., Kundu, M., Wilson, C. L., Tchkonia, T., & Kirkland, J. L.
- Affiliations
- St. Jude Children's Research Hospital (US)
- Robert and Arlene Kogod Center on Aging, Mayo Clinic Rochester Minnesota
- Mayo Clinic (US)
- Corresponding author
- Ness, Kirsten K.
- Venue
- Cancer
- Publisher
- Wiley
- Published
- 2014-12-19
- Volume
- 121
- Issue
- 10
- Pages
- 1540-1547
- ISSN
- 0008-543X (ISSN-L)
- 1097-0142
- PMC
- PMC4424063
- OpenAlex
- W1545856126
- Cited by
- 188
- References
- 95
- Citations by year
- 2026: 18 · 2025: 12 · 2024: 14 · 2023: 19 · 2022: 20 · 2021: 24 · 2020: 16 · 2019: 23 · 2018: 14 · 2017: 11 · 2016: 12 · 2015: 5
- FWCI
- 1.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (CA21765)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Childhood Cancer Survivors' Quality of Life
- Health Sciences › Medicine › Geriatrics and Gerontology › Frailty in Older Adults
- Health Sciences › Medicine › Oncology › Cancer survivorship and care
- Keywords
- frailty, childhood cancer survivors, young adults, chronic disease, mortality, physical fitness, muscle weakness, cognitive decline, cranial irradiation, cellular senescence, sterile inflammation, mitochondrial dysfunction, frailty interventions, nutraceuticals, lifestyle intervention
- MeSH terms
- Adult, Child, Chronic Disease, Humans, Inflammation, Mitochondria, Neoplasms, Risk Factors, Incidence, Cranial Irradiation, Cellular Senescence, Exercise Tolerance, Survivors, Hand Strength, Muscle Weakness, Dietary Supplements, Risk Reduction Behavior, Cognitive Dysfunction
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