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Chemotherapy pushes cells into senescence: they stop dividing but stay alive and keep releasing inflammatory signals. The usual marker, p16INK4a in blood T cells, rises sharply during treatment and is still raised a year later. In one study the rise matched about fifteen years of ordinary ageing, in another the gap in survivors was larger still.
p16INK4a expression in peripheral blood T lymphocytes rises with chronological age and is used as a measure of senescent-cell burden. In 33 women with stage I to III breast cancer sampled before anthracycline chemotherapy, immediately after, and at three and twelve months, the median rise in log2 p16INK4a was 0.81 (interquartile range 0.28 to 1.62), a 75 per cent absolute increase, which the authors state is equivalent to the increase seen over 14.7 years of chronological ageing. ARF rose comparably. Expression remained elevated twelve months after treatment ended, so this is not a transient effect of being unwell.
In a separate cohort of 60 young adult survivors of childhood, adolescent and young adult cancer compared with 29 age-matched controls at a median age of 21 years, p16INK4a was 9.6 against 8.9 log2 units (P = 0.005), which the authors describe as a 25-year age acceleration. Nine of those survivors met the criteria for frailty, and their p16INK4a was 10.5 against 9.5 log2 units in robust survivors (P = 0.055), described as a 35-year acceleration. Nine newly diagnosed children sampled before and after therapy rose from 7.3 to 8.9 log2 units (P = 0.002).
The measurements are consistent in direction and large in size. They are also small studies using one marker in one tissue, the reported age equivalents are extrapolations from a cross-sectional age curve rather than observed ageing, and no trial has shown that lowering p16INK4a changes a person's health. That gap is the reason senolytics are being tested and the reason they cannot yet be recommended.
Genotoxic chemotherapy activates the p16INK4a/RB and p53/p21 arrest programmes. Arrested cells persist and secrete the senescence-associated secretory phenotype, a mixture of interleukins, chemokines and matrix metalloproteinases that drives local inflammation and, in animal models, several features of ageing.
Query for this technology: (TITLE:"therapy-induced senescence" OR ABSTRACT:"therapy-induced senescence" OR TITLE:"p16INK4a expression" OR ABSTRACT:"p16INK4a expression" OR TITLE:"senescent cell burden" OR ABSTRACT:"senescent cell burden") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Senescent cells and p16 after chemotherapy, not a curated reading list.
Shares Epigenetic age after cancer treatment, What actually works after treatment, Late effects and survivorship toxicity, Survivorship care and late-effects surveillance and the tags rejuvenation, survivorship, biological-ageing, biomarker.
Shares Epigenetic age after cancer treatment, Frailty and late effects in survivors, What actually works after treatment, Late effects and survivorship toxicity and the tags rejuvenation, survivorship, biological-ageing.
Shares What actually works after treatment, Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Survivorship and late effects are neglected and the tags rejuvenation, survivorship.
Shares What actually works after treatment, Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Toxicity and quality of life are undervalued and the tags rejuvenation, survivorship.
Shares What actually works after treatment, Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Survivorship and late effects are neglected and the tags rejuvenation, survivorship.
Shares What actually works after treatment, Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Survivorship and late effects are neglected and the tags rejuvenation, survivorship.
Shares What actually works after treatment, Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Survivorship and late effects are neglected and the tags rejuvenation, survivorship.
Shares What actually works after treatment, Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Survivorship and late effects are neglected and the tags rejuvenation, survivorship.