Aging and cancer最新文献

Background

Lung cancer (LC) and respiratory failure (RF) are leading causes of adult mortality worldwide. Analyzing long-term mortality trends across demographic, racial, geographic, and socioeconomic groups is essential to address disparities and enhance outcomes. This study investigates US national mortality patterns for LC and RF from 1999 to 2023, focusing on changes in age-adjusted mortality rates (AAMRs) and key disparities.

Methods

Mortality data from the CDC WONDER database (1999–2023) for adults aged 25+ with LC (ICD-10: C34) or RF (ICD-10: J96) were analyzed. AAMRs per 100,000 were calculated, stratified by gender, race/ethnicity, region, state, and urban–rural status. Temporal trends were assessed using Joinpoint regression to estimate annual percent changes (APCs) with 95% confidence intervals (CIs), with significance at p < 0.05.

Results

Over 1999–2023, 456,325 deaths from LC and RF were recorded. AAMRs declined from 1999 to 2010 (APC = −1.2, 95% CI: −1.6 to −0.9) but rose from 2010 to 2023 (APC = 1.4, 95% CI: 1.1–1.7). Men's AAMRs steadily decreased, whereas women's dropped initially, then increased from 2011 to 2023 (APC = 2.0, 95% CI: 1.7 to 2.5). Non-Hispanic Whites saw a sharp AAMR rise from 2014 to 2017 (APC = 2.7, 95% CI: 0.9 to 3.3), with other racial/ethnic groups showing mixed trends. Regionally, the Northeast had the highest AAMRs (8.6, 95% CI: 8.5 to 8.7), and the Midwest the lowest (7.1, 95% CI: 7.0 to 7.1). Metropolitan areas saw increases post-2006, whereas nonmetropolitan areas rose after 2009 (APC = 2.3, 95% CI: 1.8–3.1). Mississippi had the highest state AAMR (14.0, 95% CI: 13.7–14.4), Wisconsin the lowest (3.7, 95% CI: 3.5–3.8).

Conclusion

LC and RF mortality declined until 2010, then increased, revealing significant disparities. Targeted interventions are critical to address these trends and reduce inequities.

Background

Breast cancer is a multifactorial disease that affects many women worldwide. Age is the most important risk factor for breast cancer, with an increased incidence markedly after the age of 50. The relationships of aging to breast cancer have been thoroughly examined, and notable connections regarding various age-related changes in breast tissue, as well as age-related hormonal changes, have been defined, increasing the risk of breast cancer. In order to create opportunities for early detection and prevention, it is vital that we understand the risk factors of breast cancer, including hypertension and physical activity, to name only a few factors.

Methods

This review examines breast cancer incidence and rate, associations of aging and breast cancer, and the significance of better understanding this connection. The review will consider how aging interacts with breast cancer risk and will review breast cancer biology, examination of breast tissue, hormone changes with age, and other age-related factors that may influence breast cancer risk and/or development. We will also explore breast cancer risk factors, including genetic constitution and lifestyle factors, and how these factors all interact with age characteristics. In addition, we will review strategies to reduce the risk of breast cancer and briefly review breast cancer screening guidelines, not limited to but including some of the difficulties of appropriate screening for an older woman.

Results

In summary, this review serves to underscore the awareness and understanding of breast cancer in connection with aging, and by acknowledging risk factors, flattening the curve of acceptance, and encouraging early detection and intervention through appropriate screening, we may alleviate the burden of breast cancer in older women.

Background

Cancer predominantly affects older individuals, with age being a significant risk factor for cancer incidence and metastasis. Biological sex also plays a crucial role in influencing metastasis and survival outcomes. In colorectal cancer (CRC), both the incidence and mortality from metastatic disease are higher in males relative to females.

Aim

The aim of this study was to use a syngeneic murine intraperitoneal (i.p.) metastasis model of CRC (MC-38 cells) to compare disease burden between young and aged female and male mice.

Methods

MC-38 cells tagged with red fluorescent protein were injected i.p. and tumor burden quantified longitudinally and at endpoint. As the peritoneal mesothelial cell is the initial site of tumor:host interaction in i.p. metastasis, primary murine peritoneal mesothelial cells were subjected to bottom up proteomic analysis to identify proteins differentially expressed among the cohorts.

Results

Recapitulating human epidemiological data, aged male mice exhibited the highest i.p. metastatic burden. Proteomic results identified multiple differentially expressed proteins. Protein tyrosine phosphatase 4A1 (PTP4A1), highly overexpressed in the male aged cohort relative to male young, female aged or female young, was chosen for further study. Functional analyses indicated that PTP4A1 promotes cancer:mesothelial adhesion and a small molecule inhibitor of PTP4A1, designated CMPD-43, reduced RhoA activity and inhibited heterotypic cell adhesion.

Conclusion

These results provide a resource for comparative proteomics of the peritoneal mesothelial cell in sex- and age-based cohorts. Functional data support further consideration of PTP4A1 as a potential therapeutic target for impeding CRC metastasis particularly in an aged male cohort.

In this case report, we present the clinical course of an 88-year-old woman with chronic pelvic pain attributed to an incidental benign mature cystic ovarian teratoma on imaging and discuss common imaging modalities and discussions with patients, along with the diagnostic workup.

Purpose

To assess the long-term effects of a community cancer exercise program on quality of life, fatigue, weight, waist circumference, physical activity levels, lower extremity strength, body mass index (BMI), heart rate, and blood pressure, across non-metastatic and metastatic patients.

Methods

A total of 918 participants (F/M: 1.77; mean age = 61 years, SD = 13.233) diagnosed with cancer within the last five years completed a 12-session guided physical activity program. Sessions included functional, aerobic, and resistance training aligned with ACSM guidelines for cancer patients. Blood pressure, quality of life, fatigue, BMI, lower extremity strength, body weight, and physical activity levels were measured at baseline, 12 sessions, and at 6 months, and 12 months during follow-up. The Wilcoxon signed-rank test was used to assess changes over time.

Results

Significant improvements were observed in physical activity levels, health-related quality of life, and overall quality of life, sustained at 6- and 12-month follow-ups. Waist circumference, fatigue, and blood pressure significantly decreased across all time points. Lower extremity strength improved up to 6 months but was not significant at 12 months. No significant changes were observed in body weight or BMI. Non-metastatic patients experienced significant improvements in blood pressure, waist circumference, fatigue, and functional ability, while metastatic patients maintained their baseline health measures, suggesting a stabilizing effect.

Conclusions

This study demonstrates that a community-based exercise program benefits non-metastatic cancer patients by improving quality of life, physical activity levels, and functional health, while helping metastatic patients maintain health outcomes. These findings highlight the importance of structured exercise programs in cancer care and support their implementation in real-world settings.

Background

Aging significantly affects the structural and functional integrity of the blood–brain barrier (BBB), increasing the susceptibility of the central nervous system (CNS) to both primary and metastatic cancers. As the BBB deteriorates, it promotes tumor cell infiltration, alters drug permeability, and contributes to a proinflammatory microenvironment that supports tumor progression. These age-related changes present major obstacles in the effective treatment of CNS malignancies in elderly patients.

Methods

This review synthesizes current literature on the mechanisms of BBB aging and its impact on CNS cancer development and treatment. It examines key structural alterations, such as tight junction protein loss, endothelial dysfunction, and pericyte reduction, as well as functional changes including impaired immune regulation and transporter dysfunction. The review also evaluates therapeutic challenges and emerging strategies to overcome the BBB barrier in the aging brain.

Results

Aging induces BBB dysfunction by weakening cellular junctions, disrupting the neurovascular unit, and promoting chronic neuroinflammation. These alterations facilitate tumor cell entry and survival in the brain and reduce the effectiveness of cancer therapies due to impaired drug delivery. Promising interventions, including nanoparticle-based therapies, focused ultrasound techniques, and targeted chemoimmunotherapy, are under development to enhance therapeutic outcomes in elderly patients.

Conclusion

The age-related breakdown of the BBB contributes significantly to increased cancer risk and therapeutic resistance in the CNS. Addressing BBB dysfunction through age-specific interventions and advanced drug delivery strategies is critical to improving outcomes for older adults with CNS malignancies. Further research into the molecular pathways of BBB aging will support the development of personalized and effective treatments.

Background

Cancer's inherent ability to evolve presents significant challenges for its categorization and treatment. Cancer evolution is driven by genetic, epigenetic, and phenotypic diversity influenced by microenvironment changes. Aging plays a crucial role by altering the microenvironment and inducing substantial genetic and epigenetic heterogeneity within an individual's somatic cells even before cancer initiation.

Objectives

This review highlights the clinical significance of epigenetic mechanisms in cancer evolution, focusing on hematopoietic and solid tumors. The review aims to explore opportunities for integrating evolutionary principles and data science into cancer research.

Methods

The review synthesizes recent advancements in omics technologies, single-cell sequencing, and genetic barcoding to elucidate epigenetic mechanisms and aging's role in cancer evolution.

Results

Epigenetic mechanisms' high plasticity generates heritable phenotypic diversity, driving malignant evolution toward poor prognosis. Advances in single-cell sequencing and genetic barcoding enable the precise detection and tracking of biomarkers, allowing early, personalized interventions. Incorporating data science into cancer research has the potential to map, predict, and prevent cancer evolution effectively.

Conclusion

Understanding cancer evolution through novel technologies and data analysis offers a proactive approach to cancer prevention and treatment. By predicting key evolutionary events and leveraging personalized strategies, patient outcomes can be improved, and healthcare burdens reduced, marking a transformative shift in oncology.

Background

Lung cancer is the leading cause of cancer death in the world. While cigarette smoking is the major preventable factor for cancers in general and lung cancer in particular, old age is also a major risk factor. Aging-related chronic, low-level inflammation, termed inflammaging, has been widely documented; however, it remains unclear how inflammaging contributes to increased lung cancer incidence.

Aim

The aim of this study was to establish connections between aging-associated changes in the lungs and cancer risk.

Methods

We analyzed public databases of gene expression for normal and cancerous human lungs and used mouse models to understand which changes were dependent on inflammation, as well as to assess the impact on oncogenesis.

Results

Analyses of GTEx and TCGA databases comparing gene expression profiles from normal lungs, lung adenocarcinoma, and lung squamous cell carcinoma of subjects across age groups revealed upregulated pathways such as inflammatory response, TNFA signaling via NFκB, and interferon-gamma response. Similar pathways were identified comparing the gene expression profiles of young and old mouse lungs. Transgenic expression of alpha 1 antitrypsin (AAT) partially reverses increases in markers of aging-associated inflammation and immune deregulation. Using an orthotopic model of lung cancer using cells derived from EML4-ALK fusion-induced adenomas, we demonstrated an increased tumor outgrowth in lungs of old mice while NLRP3 knockout in old mice decreased tumor volumes, suggesting that inflammation contributes to increased lung cancer development in aging organisms.

Conclusions

These studies reveal how expression of an anti-inflammatory mediator (AAT) can reduce some but not all aging-associated changes in mRNA and protein expression in the lungs. We further show that aging is associated with increased tumor outgrowth in the lungs, which may relate to an increased inflammatory microenvironment.