Aging and Cancer

Journal Information
ISSN / EISSN : 2643-8909 / 2643-8909
Published by: Wiley-Blackwell (10.1002)
Total articles ≅ 16
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, Federico Rea, Claudia Santucci, Carlo La Vecchia, Paolo Boffetta, Giovanni Corrao
Published: 19 September 2021
Abstract:
Aims 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. Methods 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. Results 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. Conclusions 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.
Edmund Charles Jenkins, Mrittika Chattopadhyay,
Published: 6 August 2021
Abstract:
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 (UPRmt). The UPRmt 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 UPRmt acts to compensate for the loss of SIRT3 observed with age, and becomes the dominant axis of the UPRmt 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.
, David A. Hutton, Sophia A. Mahoney,
Published: 22 June 2021
Aging and Cancer, Volume 2, pp 45-69; https://doi.org/10.1002/aac2.12033

Abstract:
Cardiovascular diseases (CVD) are the leading cause of death worldwide, and age is by far the greatest risk factor for developing CVD. Vascular dysfunction, including endothelial dysfunction and arterial stiffening, is responsible for much of the increase in CVD risk with aging. A key mechanism involved in vascular dysfunction with aging is oxidative stress, which reduces the bioavailability of nitric oxide (NO) and induces adverse changes to the extracellular matrix of the arterial wall (e.g., elastin fragmentation/degradation, collagen deposition) and an increase in advanced glycation end products, which form crosslinks in arterial wall structural proteins. Although vascular dysfunction and CVD are most prevalent in older adults, several conditions can “accelerate” these events at any age. One such factor is chemotherapy with anthracyclines, such as doxorubicin (DOXO), to combat common forms of cancer. Children, adolescents, and young adults treated with these chemotherapeutic agents demonstrate impaired vascular function and an increased risk of future CVD development compared with healthy age-matched controls. Anthracycline treatment also worsens vascular dysfunction in midlife (50–64 years of age) and older (65 and older) adults such that endothelial dysfunction and arterial stiffness are greater compared to age-matched controls. Collectively, these observations indicate that use of anthracycline chemotherapeutic agents induces a vascular aging-like phenotype and that the latter contributes to premature CVD in cancer survivors exposed to these agents. Here, we review the existing literature supporting these ideas, discuss potential mechanisms as well as interventions that may protect arteries from these adverse effects, identify research gaps, and make recommendations for future research.
Xiaoyang Li, Lin Cheng, Junmin Li,
Published: 20 June 2021
Aging and Cancer, Volume 2, pp 36-44; https://doi.org/10.1002/aac2.12032

Abstract:
The immune system of elderly individuals behaves differently from young adults, leading to a general assumption that the decline of immune system function increases the susceptibility to infectious and noninfectious diseases. This age-related internal immune function failure, termed "immune senescence," contributes to the increment of morbidity and mortality associated with diseases in elderly populations. Cord blood is considered as a source of “young” immune cells for anti-infectious immunity and adoptive cancer immunotherapy. In this review, we describe immune aging and the application of cord blood for replenishing aging immune cells against neoplastic diseases.
Chelsea G. Goodenough, Robyn E. Partin,
Published: 20 May 2021
Aging and Cancer, Volume 2, pp 13-35; https://doi.org/10.1002/aac2.12027

Abstract:
Skeletal muscle (muscle) is essential for physical health and for metabolic integrity, with sarcopenia (progressive muscle mass loss and weakness), a precursor of aging and chronic disease. Loss of lean mass and muscle quality (force generation per unit of muscle) in the general population are associated with fatigue, weakness, and slowed walking speed, eventually interfering with the ability to maintain physical independence, and impacting participation in social roles and quality of life. Muscle mass and strength impairments are also documented during childhood cancer treatment, which often persist into adult survivorship, and contribute to an aging phenotype in this vulnerable population. Although several treatment exposures appear to confer increased risk for loss of mass and strength that persists after therapy, the pathophysiology responsible for poor muscle quantity and quality is not well understood in the childhood cancer survivor population. This is partly due to limited access to both pediatric and adult survivor muscle tissue samples, and to difficulties surrounding noninvasive investigative approaches for muscle assessment. Because muscle accounts for just under half of the body's mass and is essential for movement, metabolism, and metabolic health, understanding mechanisms of injury responsible for both initial and persistent dysfunction is important and will provide a foundation for intervention. The purpose of this review is to provide an overview of the available evidence describing associations between childhood cancer, its treatment, and muscle outcomes, identifying gaps in current knowledge.
Lauren T. Reiman, Zachary J. Walker, Lyndsey R. Babcock, Peter A. Forsberg, Tomer M. Mark,
Published: 16 February 2021
Aging and Cancer, Volume 2, pp 6-12; https://doi.org/10.1002/aac2.12022

Abstract:
The treatment of older persons with cancer is fraught by a delicate balance of targeting the disease while avoiding treatment‐related complications. “Personalized,” or “precision” medicine approaches can ease this problem through more efficacious and less toxic treatments. Multiple myeloma epitomizes the struggle to balance treatment options and their complications, for it is an incurable disease afflicting a predominantly aged population, and treatment is administered on a continuous schedule with little or no breaks. Over the last two decades, advances in drug development have improved outcomes for younger, fit patients, but older, frail patients have not realized the same benefit. This could be related to the benefits of three drug combinations, when frail patients can often tolerate only two drugs at a time. In myeloma, personalized approaches have lagged behind some other malignancies due to its genetic complexity and a paucity of abnormalities with associated targeted therapies. In contrast, the disease is managed with an array of drugs that target phenotypic characteristics common in malignant plasma cells. To address the unmet need for personalized medicine in myeloma, we developed a functional approach by profiling the sensitivity of patients’ myeloma to clinically available drugs. Through this, we observed that receiving at least two effective drugs portended better outcomes, leaving those patients who can only tolerate two drug regimens without room for error. We now describe a frail patient's case and their drug sensitivity profile to illustrate how personalized treatment could have led to an improved disease course. Personalized treatment could provide the greatest survival improvements to older adults with cancers, such as multiple myeloma, through avoiding undertreatment, limiting attrition through subsequent lines of therapy, reducing exposure to ineffective drugs and streamlining the management of relapses. Exploring these avenues is imperative to closing the gap of cancer‐related mortality in older and frail persons.
Fabio Marongiu,
Published: 24 October 2020
Aging and Cancer, Volume 1, pp 45-57; https://doi.org/10.1002/aac2.12021

Abstract:
There is now sufficient evidence to indicate that aging is associated with the emergence of a clonogenic and neoplastic‐prone tissue landscape, which fuels early stages of cancer development and helps explaining the rise in cancer incidence and mortality in older individuals. Dietary interventions are among the most effective approaches to delay aging and age‐related diseases, including cancer. Reduced caloric intake has been, historically, the most intensely investigated strategy. Recent findings point to a critical role of a long fasting interval in mediating some of the beneficial effects of caloric restriction. Time‐restricted feeding, intermittent fasting, and fasting mimicking diets are being proposed for their potential to prolong healthy life span and to delay late‐onset diseases such as neoplasia. Evidence will be discussed suggesting that the effects of these dietary regimens are mediated, at least in part, through retardation of age‐related functional changes at cell and tissue level, including a delay in the emergence of the neoplastic‐prone tissue microenvironment.
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