Aging and cancer最新文献

{"title":"Increased risk of cancer in dogs and humans: A consequence of recent extension of lifespan beyond evolutionarily determined limitations?","authors":"Aaron L. Sarver,&nbsp;Kelly M. Makielski,&nbsp;Taylor A. DePauw,&nbsp;Ashley J. Schulte,&nbsp;Jaime F. Modiano","doi":"10.1002/aac2.12046","DOIUrl":"10.1002/aac2.12046","url":null,"abstract":"<p>Cancer is among the most common causes of death for dogs (and cats) and humans in the developed world, even though it is uncommon in wildlife and other domestic animals. We provide a rationale for this observation based on recent advances in our understanding of the evolutionary basis of cancer. Over the course of evolutionary time, species have acquired and fine-tuned adaptive cancer-protective mechanisms that are intrinsically related to their energy demands, reproductive strategies, and expected lifespan. These cancer-protective mechanisms are general across species and/or specific to each species and their niche, and they do not seem to be limited in diversity. The evolutionarily acquired cancer-free longevity that defines a species’ life history can explain why the relative cancer risk, rate, and incidence are largely similar across most species in the animal kingdom despite differences in body size and life expectancy. The molecular, cellular, and metabolic events that promote malignant transformation and cancerous growth can overcome these adaptive, species-specific protective mechanisms in a small proportion of individuals, while independently, some individuals in the population might achieve exceptional longevity. In dogs and humans, recent dramatic alterations in healthcare and social structures have allowed increasing numbers of individuals in both species to far exceed their species-adapted longevities (by two to four times) without allowing the time necessary for compensatory natural selection. In other words, the cancer-protective mechanisms that restrain risk at comparable levels to other species for their adapted lifespan are incapable of providing cancer protection over this recent, drastic, and widespread increase in longevity.</p>","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"3 1","pages":"3-19"},"PeriodicalIF":0.0,"publicationDate":"2022-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9387675/pdf/nihms-1778919.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10810844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical activity and fitness in childhood cancer survivors: A scoping review","authors":"Matthew D. Wogksch,&nbsp;Chelsea G. Goodenough,&nbsp;Emily R. Finch,&nbsp;Robyn E. Partin,&nbsp;Kirsten K. Ness","doi":"10.1002/aac2.12042","DOIUrl":"10.1002/aac2.12042","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Estimates indicate that nearly 8% of the over 500,000 survivors of childhood cancer living in the United States are frail in their fourth and fifth decades of life, a phenotype typically seen in geriatric populations. Participation in regular physical activity to improve physical fitness in healthy and diseased populations reduces risk for frail health by increasing physiologic reserve. However, physical activity may not have the same effects on fitness in childhood cancer survivors as it does among their peers with no cancer history.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This scoping review seeks to describe associations between physical activity, physical fitness, chronic disease, and mortality in childhood cancer survivors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Relevant literature was identified through a comprehensive search in the PubMed, Web of Science, CINAHL, and Cochrane databases. A narrative synthesis was performed on observational studies that had physical activity or physical fitness clearly defined and compared with chronic disease outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 595 studies were screened, and results from 11 studies are presented. Childhood cancer survivors who participate in regular physical activity have improved markers of cardiovascular health, decreased risk of overt cardiovascular disease, and decreased risk of all-cause mortality compared to survivors who are not physically active. Childhood cancer survivors who are physically fit have increased neurocognition, and decreased risk of all-cause mortality compared to survivor's who are not fit. The differential effects of physical activity on fitness and health among childhood cancer survivors when compared to peers is potentially related to treatment exposures that damage cardiovascular tissue and impact regenerative potential.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Research is needed to determine the optimal timing, frequency, intensity, and duration of physical activity necessary to optimize fitness in childhood cancer survivors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"2 4","pages":"112-128"},"PeriodicalIF":0.0,"publicationDate":"2021-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8794406/pdf/nihms-1772678.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10399994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FOXO3 regulates a common genomic program in aging and glioblastoma stem cells","authors":"Amanda J. Audesse,&nbsp;Galina Karashchuk,&nbsp;Zachary A. Gardell,&nbsp;Nelli S. Lakis,&nbsp;Sun Y. Maybury-Lewis,&nbsp;Abigail K. Brown,&nbsp;Dena S. Leeman,&nbsp;Yee Voan Teo,&nbsp;Nicola Neretti,&nbsp;Douglas C. Anthony,&nbsp;Alexander S. Brodsky,&nbsp;Ashley E. Webb","doi":"10.1002/aac2.12043","DOIUrl":"10.1002/aac2.12043","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Glioblastoma (GBM) is an aggressive, age-associated malignant glioma that contains populations of cancer stem cells. These glioma stem cells (GSCs) evade therapeutic interventions and repopulate tumors due to their existence in a slowly cycling quiescent state. Although aging is well known to increase cancer initiation, the extent to which the mechanisms supporting GSC tumorigenicity are related to physiological aging remains unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Here, we investigate the transcriptional mechanisms by which Forkhead Box O3 (FOXO3), a transcriptional regulator that promotes healthy aging, affects GSC function and the extent to which FOXO3 transcriptional networks are dysregulated in aging and GBM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>We performed transcriptome analysis of clinical GBM tumors and observed that high FOXO3 activity is associated with gene expression signatures of stem cell quiescence, reduced oxidative metabolism, and improved patient outcomes. Consistent with these findings, we show that elevated FOXO3 activity significantly reduces the proliferation of GBM-derived GSCs. Using RNA-seq, we find that functional ablation of FOXO3 in GSCs rewires the transcriptional circuitry associated with metabolism, epigenetic stability, quiescence, and differentiation. Since FOXO3 has been implicated in healthy aging, we then investigated the extent to which it regulates common transcriptional programs in aging neural stem cells (NSCs) and GSCs. We uncover a shared transcriptional program and, most strikingly, find that FOXO3-regulated pathways are associated with altered mitochondrial functions in both aging and GBM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This work identifies a FOXO-associated transcriptional program that correlates between GSCs and aging NSCs and is enriched for metabolic and stemness pathways connected with GBM and aging.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"2 4","pages":"137-159"},"PeriodicalIF":0.0,"publicationDate":"2021-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9601604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10513726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term analysis of irradiated skin after breast-conserving surgery in breast cancer patients using noninvasive imaging","authors":"Kasumi Mikami,&nbsp;Maiko Kitajima,&nbsp;Yuka Noto,&nbsp;Chieko Itaki,&nbsp;Yasuyo Fukushi,&nbsp;Yoshiko Hirota,&nbsp;Yasushi Mariya,&nbsp;Megumi Tsushima,&nbsp;Keiichi Kattou,&nbsp;Tomohiro Osanai","doi":"10.1002/aac2.12041","DOIUrl":"10.1002/aac2.12041","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>In patients with breast cancer, skin assessment is useful for the treatment and prevention of postoperative adverse effects of radiotherapy. This study was designed to clarify the long-term changes in the irradiated skin of patients after breast-conserving surgery using visual inspection and noninvasive imaging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We compared changes in the irradiated skin over time between evaluations, based on visual inspection and noninvasive imaging in 31 patients receiving postmastectomy radiation therapy. The condition of the skin was evaluated by visual inspection of the thermogram, and analysis of skin surface temperature, intensity of erythema, intensity of melanin, and hydration level.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Skin surface temperature remained higher at the irradiation site after 11 months, despite the absence of erythema per visual inspection. The intensity of erythema was higher at the irradiated site until 17–19 months after completion of irradiation. Similarly, the intensity of melanin tended to be higher at the irradiated site compared with the nonirradiated site until 17–19 months. The hydration level at the irradiated site was lower at 6 months but recovered to match the nonirradiated site at 11–13 months. Impaired skin conditions assessed by noninvasive objective procedures persist longer than the assessment made by visual inspection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Adverse effects should be treated or prevented in the long term in patients receiving postmastectomy radiation therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"2 4","pages":"129-136"},"PeriodicalIF":0.0,"publicationDate":"2021-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/aac2.12041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48284533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An outlook on the lymph nodes dissection during the pancreatectomy for pancreatic cancer","authors":"Weishen Wang,&nbsp;Baiyong Shen","doi":"10.1002/aac2.12040","DOIUrl":"10.1002/aac2.12040","url":null,"abstract":"<p>Pancreatic cancer is likely to be one of the most highly lethal diseases in the world.<span>^{1, 2}</span> Radical pancreatectomy with adjuvant chemotherapy is a curative treatment for pancreatic cancer.<span>²</span> Lymphadenectomy is an indispensable procedure in radical resection for pancreatic cancer. It is obvious that lymph node dissection is essential. According to the eight edition of the American Joint Committee on Cancer (AJCC) tumor node metastasis (TNM) staging system, the number of positive lymph nodes (PLNs) is related to the prognosis of the patients.<span>³</span> Moreover, a standard lymphadenectomy reduces the incidence of local lymph node recurrence.<span>^{4, 5}</span> However, in some cases, the current guidelines or consensus cannot be satisfied in clinical practice. Thus, in this brief literature review, we summarize the current status of lymph nodes dissection in pancreatectomy while focusing on the further development of research.</p><p>The AJCC TNM staging system is the most worldwide used system that provides us a relatively accurate prognosis of the patients. The latest version is the eight edition of the TNM staging system.<span>³</span> The main revision to the seventh edition is the modification of the N status in the system. Previously, in the seventh edition, the N status was separated into N0/N1 depending on whether regional metastatic lymph nodes were found in the operation. The impact of the number of PLNs on the prognosis was ignored. Currently, in the eight edition, the N status is divided into N0/N1/N2 based on the number of PLNs. The patients without lymph node metastasis are stated in the N0 stage. The patients with four or more PLNs are classified into the N2 stage, which implied poor survival. The rest are in the N1 stage whose PLNs are less than four.</p><p>In order to acquire accurate PLNs, a certain number of lymph nodes should be harvested. The optimal lymphadenectomy was disputed until a consensus statement on the extent of lymphadenectomy for pancreatectomy was published by the International Study Group on Pancreatic Surgery (ISGPS) in 2014.<span>⁴</span> In this statement, the study group has affirmed the extent of lymph node dissection for the pancreatectomy. Based on the nomenclature for nodal stations of the Japanese Pancreas Society,<span>⁶</span> a standard lymphadenectomy should include lymph node stations 5, 6, 8a, 12b1, 12b2, 12c, 13a, 13b, 14a right lateral side, 14b right lateral side, 17a, and 17b during the pancreatoduodenectomy (PD), while a standard lymphadenectomy during the distal pancreatectomy should include lymph node stations 10, 11 and 18 for the tumor located in the body and tail of the pancreas. Furthermore, the minimal number of examined lymph nodes (MNELN) for the PD was considered to be at least 15. With the increase of the number of regional lymph nodes retrieved, the accuracy of PLNs raised up.<s","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"2 4","pages":"107-111"},"PeriodicalIF":0.0,"publicationDate":"2021-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/aac2.12040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49206462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Flatten the rising incidence of cancer due to aging","authors":"Samuel Waxman","doi":"10.1002/aac2.12039","DOIUrl":"10.1002/aac2.12039","url":null,"abstract":"<p>As an oncologist engaged for 45 years in providing ongoing patient care I witnessed a cancer treatment revolution. Multiple options to conventional cytotoxic chemotherapy emerged that led to changing cancer from a rapid fatal disease to a more treatable chronic ailment.  Science was paying off by diminishing the catastrophic effect of cancer for a large number of patients. More people were being cured with less toxic treatments. A significant gain in outcome BUT, my patients were returning with late onset metastases and new primary cancers, this time more difficult to treat and often  associated with the  comorbidities of AGING. This scenario is a global experience. Cancer incidence is increasing in most forms of cancer and mortality rates rising relentlessly with increasing age. The reality is that understanding AGE-related cancer, its evolution, interplay, clinical recognition, and management is underfunded and is an unmet clinical need. As recently as 2015, there has been minimal interactions between the National Cancer Institute and the National Aging Institute to promote research at the interface of aging and cancer, despite the overt links between these processes. Indeed, a major DISPARITY both in research and treating age-related cancer exists.</p><p>Yet, ANSWERS are within reach to guide collaborative research to flatten the rising incidence of cancer due to aging. A more holistic view for how aging impacts cancer gaining ground. Aging stem and progenitor cells strive to survive in a changing and often hostile aging stromal environment. This results in somatic variants, epigenetic compensations, loss of gene stability due to DNA damage, and mechanisms to resist exhaustion and death such as reducing immune recognition and hijacking senescence and autophagy  pathways for survival. These changes may be apparent by measurement of clonal progenitor populations with mutations allowing epigenetic driven pathways and cell cycle alterations to emerge to create a survival advantage. Is this privileged and more compensated AGED cell an outlier that is already on a path to cancer clonal evolution and can this be prevented? Clinical and laboratory evidence supports this and  collaborative research is providing models to understand ways to recognize this  transition and identify this threat with precision in the aging cell population. Interventions to diminish age as a risk factor for cancer include education on the importance of “Healthy Aging” and laboratory measurements to distinguish a healthy aged tissue from one with cancerous clonal evolution. Therapeutic interventions to diminish  cancer development in the AGED cell population include early clinical screening, senolytics, specific inhibitors of cell cycle mediators of autophagy, PARP inhibitors, and identifying specific dietary and metabolic dependencies needed to prevent cancer transformation. This type of early screening of AGING stem cells and progenitors and evolving clonal cancer cells ","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"2 3","pages":"73"},"PeriodicalIF":0.0,"publicationDate":"2021-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/aac2.12039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50805305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Introduction to the third issue of Aging and Cancer","authors":"Doris Germain PhD","doi":"10.1002/aac2.12038","DOIUrl":"10.1002/aac2.12038","url":null,"abstract":"<p>Dr. Samuel Waxman has dedicated his career to the treatment of cancer patients and to cancer research. While he led an extraordinarily successful medical practice for 45 years, he understood very early that knowledge is power and that without research, cancer treatment would remain highly toxic.</p><p>His passion for research is best illustrated by the creation of the Samuel Waxman Cancer Research Foundation (SWCRF) in 1976. The SWCRF currently funds a network of 30 researchers across the world and raised over $100 million for cancer research.</p><p>To this day, the passion of this remarkable physician-scientist has only become stronger. His most recent goal is to understand the link between cancer and aging. While cancer is known to be an age-related disease, surprisingly, little research focuses on how and why cancer is more frequent in older individuals.</p><p>Dr. Waxman has, therefore, not only established collaboration between his foundation and the National Institute of Aging to specifically fund research projects aimed at understanding the link between aging and cancer but also teamed up with Wiley Publishing to launch this new journal in 2020.</p><p>In this third edition of <i>Aging and Cancer</i>, three articles from SWCRF investigators were selected to illustrate the range of questions and approaches needed to cover the complexity of the link between aging and cancer.</p><p>The first article by our group (Jenkins et al. Are the estrogen receptor and SIRT3 axes of the mitochondrial UPR key regulators of breast cancer sub-type determination according to age? Aging and Cancer, 2021. https://doi.org/10.1002/aac2.12035) focuses on the counterintuitive observation that breast cancer in post-menopausal women, which have much lower levels of circulating estrogen due to the cessation of ovarian function at menopause, tends to develop cancers that show elevated expression of the estrogen receptor.</p><p>The second article by Edward Evans and SWCRF investigator James DeGregori (Evans et al. Cells with Cancer-associated Mutations Overtake Our Tissues as We Age. Aging and Cancer, 2021) uses an unbiased approach of a meta-analysis of published sequencing data on normal tissues to determine how many cancer-associated mutations are present in cancer-free individuals with age. They present evidence that these mutations are actually found at high frequency across tissues. This finding immediately raises the question as to why some individuals go on to develop cancer, while others do not.</p><p>In direct line with the Evans study, the third article by SWCRF-associated investigator Paolo Boffetta and colleagues (Franchi et al. Developing a multimorbidity prognostic score in elderly patients with solid cancer using administrative databases from Italy. <i>Aging and Cancer</i>, 2021) takes an epidemiological approach to interrogate multiple conditions and their association with Cancer Multimorbidity Score (CMS). Their study suggests that the CMS may be use","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"2 3","pages":"74"},"PeriodicalIF":0.0,"publicationDate":"2021-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/aac2.12038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43003913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cells with cancer-associated mutations overtake our tissues as we age","authors":"Edward J. Evans Jr.,&nbsp;James DeGregori","doi":"10.1002/aac2.12037","DOIUrl":"10.1002/aac2.12037","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>To shed light on the earliest events in oncogenesis, there is growing interest in understanding the mutational landscapes of normal tissues across ages. In the last decade, next-generation sequencing of human tissues has revealed a surprising abundance of cells with what would be considered oncogenic mutations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>We performed a meta-analysis on previously published sequencing data on normal tissues to categorize mutations based on their presence in cancer and showcase the quantity of cells with cancer-associated mutations in cancer-free individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>We analyzed sequencing data from these studies of normal tissues to determine the prevalence of cells with mutations in three different categories across multiple age groups: (1) mutations in genes designated as drivers, (2) mutations that are in the Cancer Gene Census (CGC), and (3) mutations in the CGC that are considered pathogenic. As we age, the percentage of cells in all three levels increase significantly, reaching over 50% of cells having oncogenic mutations for multiple tissues in the older age groups. The clear enrichment for these mutations, particularly at older ages, likely indicates a strong selection for the resulting phenotypes. Combined with an estimation of the number of cells in tissues, we calculate that most older, cancer-free individuals possess at least 100 billion cells that harbor at least one oncogenic mutation, presumably emanating from a fitness advantage conferred by these mutations that promote clonal expansion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These studies of normal tissues have highlighted the specific drivers of clonal expansion and how frequently they appear in us. Their high prevalence throughout cancer-free individuals necessitates a reconsideration of the oncogenicity of these mutations, which could shape methods of detection, prevention, and treatment of cancer, as well as of the potential impact of these mutations on tissue function and our health.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"2 3","pages":"82-97"},"PeriodicalIF":0.0,"publicationDate":"2021-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651076/pdf/nihms-1739267.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39711215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing a multimorbidity prognostic score in elderly patients with solid cancer using administrative databases from Italy","authors":"Matteo Franchi,&nbsp;Federico Rea,&nbsp;Claudia Santucci,&nbsp;Carlo La Vecchia,&nbsp;Paolo Boffetta,&nbsp;Giovanni Corrao","doi":"10.1002/aac2.12036","DOIUrl":"10.1002/aac2.12036","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To develop and to validate a Cancer Multimorbidity Score (CMS) predictive of mortality in elderly patients affected by solid tumor, by using population-based administrative Italian databases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Through administrative databases of Lombardy Region (Northern Italy), a cohort of patients aged ≥65 years with a new diagnosis of solid tumor during the period 2009–2014 was identified. Sixty-one conditions and diseases, measured from hospital inpatient diagnosis and outpatient drug prescription within 2 years before cancer diagnosis in a training set randomly including 70% of the cohort patients were tested to predict 5-year mortality using a Cox regression model. Regression coefficients were used for assigning a weight to the predictive conditions, selected by the LASSO method. Weights were summed up in order to produce an aggregate score (the CMS). CMS performance was evaluated on a validation set, including the remaining 30% of the cohort patients, in terms of discrimination and calibration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study cohort included 148,242 cancer patients. Thirty conditions were selected as independent predictors of 5-year mortality and were included in the computation of the CMS. The area under the receiving operating characteristics curve was 0.68, becoming 0.71 when considering 1-year mortality as outcome and reaching values of 0.74 and 0.81 when focusing on patients with breast and prostate cancer, respectively. A strong increasing trend in mortality was observed with increasing CMS value.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CMS represents a new useful tool for identifying high-risk elderly cancer patients in everyday clinical practice, as well as for risk adjustment in clinical and epidemiological studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"2 3","pages":"98-104"},"PeriodicalIF":0.0,"publicationDate":"2021-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/aac2.12036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45355613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are the estrogen receptor and SIRT3 axes of the mitochondrial UPR key regulators of breast cancer subtype determination according to age?","authors":"Edmund Charles Jenkins,&nbsp;Mrittika Chattopadhyay,&nbsp;Doris Germain","doi":"10.1002/aac2.12035","DOIUrl":"10.1002/aac2.12035","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Aging is a major risk factor of developing breast cancer. Despite the fact that postmenopausal women have lower levels of estrogen, older women have a higher rate of estrogen receptor alpha (ERα)-positive breast cancer. Conversely, young women who have elevated levels of estrogen tend to develop ERα-negative disease that is associated with higher rate of metastasis. This perspective proposes a unifying model centered around the importance of mitochondrial biology in cancer and aging to explain these observations. Mitochondria are essential for the survival of cancer cells and therefore pathways that maintain the functionality of the mitochondrial network in cancer cells fulfill a critical role in the survival of cancer cells. The ERα and the mitochondrial sirtuin-3 (SIRT3) have been reported to be key players of the mitochondrial unfolded protein response (UPR^mt). The UPR^mt is a complex retrograde signaling cascade that regulates the communication between the mitochondria and the nucleus to restore mitochondrial fitness in response to oxidative stress. SIRT3 is a major regulator of aging. Its level decreases with age and single-nucleotide polymorphisms that preserve its expression at higher levels are observed in centenarians. We propose a model whereby the ERα axis of the UPR^mt acts to compensate for the loss of SIRT3 observed with age, and becomes the dominant axis of the UPR^mt to maintain the integrity of the mitochondria during transformation, thus explaining the selective advantage of ERα-positive luminal cells in breast cancer arising from older women.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"2 3","pages":"75-81"},"PeriodicalIF":0.0,"publicationDate":"2021-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/aac2.12035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39602199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}