Age is essentially used in all cancer epidemiology studies and is also one of the most studied risk factors for cancer. People with cancer seem to age very rapidly, appear frail due to cancer treatment, and need assistance in daily routines.
Cancer treatments such as chemotherapy used to medicate or control cancer lead to accelerated aging in survivors. Accelerated aging phenotypes in cancer survivors consist of frailty, cognitive impairment, chronic organ dysfunction, and secondary cancers, all of which can impact long-term health and quality of life in cancer survivors.
Several aging clocks and biomarkers of aging have been suggested to be potentially helpful in estimating a person’s biological age. These biomarkers can provide specific information about the biological age independent of an individual’s chronological age.
One of these biomarkers is a protein called p16INK4a. Previous research has shown that cell cycle kinase inhibitor p16INK4a slows cell division and is produced at higher levels by cells as a person ages.
Measuring biological age in cancer survivors is significant to project the risk of cancer treatment-related comorbidities and evaluate cancer therapies’ effects to maximize treatment efficacy.
In this study, researchers investigated the correlation between p16INK4a levels in young cancer patients and survivors and accelerated aging.
Read the original publication of this study here: [Accelerated aging among childhood, adolescent, and young adult cancer survivors is evidenced by increased expression of p16INK4a and frailty]
This study aimed to assess the molecular changes in P16INK4a tumor suppressor protein in newly diagnosed cancer patients and survivors.
Accelerated aging among childhood, adolescent, and young adult cancer survivors is evidenced by increased expression of p16INK4a and frailty
Researchers from the University of North Carolina Lineberger Comprehensive Cancer Center conducted a cross‐sectional cohort of young adult survivors and age‐matched, cancer‐free controls for p16INK4a expression and frailty assessments.
In this study, 60 cancer survivors and 29 age-matched controls from ages 17-29 years underwent prospective measurements of p16INK4a expression before and after cancer therapy. Frailty was measured with a modified Fried frailty phenotype assessing sarcopenia (loss of skeletal muscle mass and strength), slowness, weakness, exhaustion, and low energy expenditure.
In addition, a prospective new diagnosis cohort among young children and adolescents aged 1-17 years newly diagnosed with cancer was tested for p16 expression. This diagnosis showed that levels of p16 before cytotoxic chemotherapy exposure treatment were frequently undetectable; however, these levels increased dramatically after chemotherapy exposure.
Results of the study propose that expression of p16INK4a was higher among cancer survivors compared with cancer-free subjects. Among the survivors, nine were frail and had higher p16INK4a expression compared with robust survivors. This increased p16INK4a expression represents a 35‐year age acceleration among frail survivors.
The accelerated aging caused by cancer survivors’ treatments could be explained by DNA damage, cellular senescence, telomere attrition, stem cell exhaustion, and epigenetic alterations.
In both the young adult survivor and newly diagnosed pediatric cohorts, the PBTL p16 levels have shown to be higher with increased treatment intensity. These results support prior findings associating treatment intensity with the degree of increased p16 expression.
Finally, this study concludes that chemotherapy is associated with molecular age and increased cellular senescence in pediatric and young adult cancer survivors. Frail survivors exhibit higher levels of p16INK4a compared with robust survivors. This finding suggests that cellular senescence may be associated with premature aging in survivors.
Takeaways:
- Cancer treatments, such as chemotherapy, are associated with accelerated aging due to increased cellular senescence.
- p16 levels were higher with increased treatment intensity.
- Compared with robust survivors, frail cancer survivors had higher p16INK4a expression exhibiting a 35‐year age acceleration.
You can read the original publication of this study here: [ Accelerated aging among childhood, adolescent, and young adult cancer survivors is evidenced by increased expression of p16INK4a and frailty ]
- Age and Cancer Risk: A Potentially Modifiable Relationship
- Cancer Treatment-Induced Accelerated Aging in Cancer Survivors: Biology and Assessment
- Cancer and its treatment may accelerate the aging process in young patients
