Chemotherapy Side-Effects: Not All DNA Damage Is Equal

Cancers, Journal Year: 2022, Volume and Issue: 14(3), P. 627 - 627

Published: Jan. 26, 2022

Recent advances have increased survival rates of children and adults suffering from cancer thanks to effective anti-cancer therapy, such as chemotherapy. However, during treatment later in life they are frequently confronted with the severe negative side-effects their life-saving treatment. The occurrence numerous features accelerated aging, seriously affecting quality life, has now become one most pressing problems associated (pediatric) Chemotherapies target damage DNA, causing mutations or genome instability, a major hallmark both aging. there types chemotherapeutic drugs that genotoxic interfere DNA metabolism different ways, each own biodistribution, kinetics, biological fate. Depending on type lesion produced (e.g., interference replication RNA transcription), organ cell inflicted cycle differentiation status, metabolic state, activity clearance detoxification mechanisms, cellular condition micro-environment), degree exposure, outcomes can largely differ. These considerations provide conceptual framework which classes chemotherapeutics contribute development toxicities aging systems. Here, we summarize observed ex-cancer patients discuss might be responsible.

Language: Английский

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Molecular mechanisms of aging and anti-aging strategies

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 24, 2024

Abstract Aging is a complex and multifaceted process involving variety of interrelated molecular mechanisms cellular systems. Phenotypically, the biological aging accompanied by gradual loss function systemic deterioration multiple tissues, resulting in susceptibility to aging-related diseases. Emerging evidence suggests that closely associated with telomere attrition, DNA damage, mitochondrial dysfunction, nicotinamide adenine dinucleotide levels, impaired macro-autophagy, stem cell exhaustion, inflammation, protein balance, deregulated nutrient sensing, altered intercellular communication, dysbiosis. These age-related changes may be alleviated intervention strategies, such as calorie restriction, improved sleep quality, enhanced physical activity, targeted longevity genes. In this review, we summarise key historical progress exploration important causes anti-aging strategies recent decades, which provides basis for further understanding reversibility phenotypes, application prospect synthetic biotechnology therapy also prospected.

Language: Английский

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Accelerated Aging in Survivors of Childhood Cancer—Early Onset and Excess Risk of Chronic Conditions

JAMA Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

Importance The lifetime risk of aging-related diseases among survivors childhood cancer, accelerated by cancer treatment exposures, is unknown. Understanding this can provide a more comprehensive assessment long-term health across the lifespan and guide adult care. Objective To estimate risks 8 treatment-related cancers cardiovascular conditions compare them with general population. Design, Setting, Participants Using data from Childhood Cancer Survivor Study national databases, simulation modeling study projected outcomes for 5-year diagnosed between 1970 1999 based on exposures age-related risks. population comparator was simulated using age-, sex-, calendar year–matched individuals who faced only Exposures Treatment era (1970s, 1980s, 1990s), original diagnosis, radiation primary diagnosis (any, none). Main Outcomes Measures Estimated (breast colorectal glial tumors, sarcomas, heart failure, coronary disease/myocardial infarction, stroke, valvular disease). Risks were compared population, stratified exposure. Results In 20% developed at least 1 condition age 65.0 years; in threshold reached 47.3 years, representing 17.7-year (95% uncertainty interval [UI], 14.0-21.0) acceleration disease onset. By 65 55% to develop condition, indicating 2.7-fold UI, 2.2-3.5) higher relative 34.2% 28.3-42.5) absolute excess those treated therapy (22.0 years earlier onset [95% 18.0-25.0]; 37.3% 31.6%-44.7%]) but still elevated without exposure (13.5 10.0-16.0]; 31.0% 23.9%-40.3%]). Reaching middle associated increased Compared 40 had 6.2-fold 4.8-9.4) developing new within 10 years. Conclusions Relevance This found that experience diseases, regardless prior These findings underscore importance prioritizing prevention decades than

Language: Английский

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Long-term Trajectories of Physical Function Decline in Women With and Without Cancer

JAMA Oncology, Journal Year: 2023, Volume and Issue: 9(3), P. 395 - 395

Published: Jan. 19, 2023

Patients with cancer experience acute declines in physical function, hypothesized to reflect accelerated aging driven by cancer-related symptoms and effects of therapies. No study has examined long-term trajectories function site, stage, or treatment compared cancer-free controls.

Language: Английский

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Accelerated Aging in Cancer Survivors: Cellular Senescence, Frailty, and Possible Opportunities for Interventions

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3319 - 3319

Published: March 14, 2024

The population of cancer survivors has markedly increased due to the rapid improvements in treatment. However, experience accelerated aging, which leads chronic diseases and other age-related conditions, such as frailty. Those conditions may persist years after diagnosis Cellular senescence, a hallmark is one mechanisms that contribute aging survivors. Several measures, including measures based on clinical markers biomarkers, have been proposed estimate process, some them shown associations with mortality frailty anti-aging interventions, lifestyle changes drugs, proposed. Future research, particularly large-scale studies, needed determine efficiency these interventions before considering their application clinics. This review focuses cellular senescence survivors, assessment process using high prevalence population, well possible opportunities for interventions. A deeper understanding will development effective strategies mitigate improve quality life.

Language: Английский

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Senolytic treatment alleviates doxorubicin‐induced chemobrain

Aging Cell, Journal Year: 2024, Volume and Issue: 23(2)

Published: Jan. 15, 2024

Abstract Doxorubicin (Dox), a widely used treatment for cancer, can result in chemotherapy‐induced cognitive impairments (chemobrain). Chemobrain is associated with inflammation and oxidative stress similar to aging. As such, Dox has also been as model of However, it unclear if induces brain changes that observed during aging since does not readily enter the brain. Rather, mechanism chemobrain likely involves induction peripheral cellular senescence release senescence‐associated secretory phenotype (SASP) factors these SASP disrupt cognition. We examined effect on markers In addition, we employed senolytic, ABT‐263, which limited access The results indicate plasma brain, activating microglia, increasing stress, altering gene transcription. turn, synaptic function required memory was reduced response altered redox signaling. ABT‐263 prevented or most Dox‐induced effects. emphasize link between decline from senescent cells some differences well similarities advanced age treatment.

Language: Английский

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Chemotherapy-Induced Cognitive Impairment and Hippocampal Neurogenesis: A Review of Physiological Mechanisms and Interventions

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(23), P. 12697 - 12697

Published: Nov. 24, 2021

A wide range of cognitive deficits, including memory loss associated with hippocampal dysfunction, have been widely reported in cancer survivors who received chemotherapy. Changes both white matter and gray volume observed following chemotherapy treatment, reduced the medial temporal lobe thought to be due part reductions neurogenesis. Pre-clinical rodent models confirm that common chemotherapeutic agents used treat various forms non-CNS cancers reduce rates neurogenesis impair performance on hippocampally-mediated learning tasks. We review pre-clinical literature identify how drugs affect induce impairment. also factors such as physical exercise environmental stimulation may protect against chemotherapy-induced neurogenic suppression neurotoxicity. Finally, we pharmacological interventions target hippocampus are designed prevent or neurotoxic side effects

Language: Английский

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The Achilles’ heel of cancer survivors: fundamentals of accelerated cellular senescence

Journal of Clinical Investigation, Journal Year: 2022, Volume and Issue: 132(13)

Published: June 30, 2022

Recent improvements in cancer treatment have increased the lifespan of pediatric and adult survivors. However, treatments accelerate aging survivors, which manifests clinically as premature onset chronic diseases, such endocrinopathies, osteoporosis, cardiac dysfunction, subsequent cancers, geriatric syndromes frailty, among others. Therefore, treatment-induced early accounts for significant morbidity, mortality, health expenditures One major mechanism driving this accelerated is cellular senescence; induce senescence tumor cells normal, nontumor tissue, thereby helping mediate several diseases. Studies on clinical monitoring therapeutic targeting made considerable progress recent years. Large-scale trials are currently evaluating senotherapeutic drugs, inhibit or eliminate senescent to ameliorate treatment-related aging. In article, we survey literature phenotypes mechanisms survivors provide an up-to-date review preclinical translational evidence a well insight into potential drugs. only with time will effect senotherapies be visible.

Language: Английский

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Inflammation and aging-related disease: A transdisciplinary inflammaging framework

GeroScience, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

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Characterizing cancer-related cognitive impairments and impact on quality of life in women with metastatic breast cancer

Breast Cancer Research and Treatment, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 13, 2024

Language: Английский

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