Aging and cancer最新文献

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.

People over 55 years old represent the majority of cancer patients and suffer from increased metastatic burden compared to the younger patient population. As the aging population increases globally, it is prudent to understand how the intrinsic aging process contributes to cancer progression. As we age, we incur aberrant changes in the extracellular matrix (ECM) of our organs, which contribute to numerous pathologies, including cancer. Notably, the lung, liver, and bone represent the most common sites of distal metastasis for all cancer types. In this review, we describe how age-dependent changes in the ECM of these organs influence cancer progression. Further, we outline how these alterations prime the premetastatic niche and why these may help explain the disparity in outcome for older cancer patients.

The life expectancy of the world's elderly population (65 and older) continues to reach new milestones with older individuals currently comprising greater than 8.5% (617 million) of the world's population. This percentage is predicted to approach 20% of the world's population by 2050 (representing 1.6 billion people). Despite this amazing feat, many healthcare systems are not equipped to handle the multitude of diseases that commonly manifest with age, including most types of cancers. As the world's aging population grows, cancer treatments continue to evolve. Immunotherapies are a new drug class that has revolutionized our ability to treat previously intractable cancers; however, their efficacy in patients with compromised immune systems remains unclear. In this review, we will discuss how aging-associated losses in immune homeostasis impact the efficacy and safety of immunotherapy treatment in preclinical models of aging. We will also discuss how these findings translate to elderly patients receiving immunotherapy treatment for refractory and relapsed cancers, as well as, strategies that could be explored to improve the efficacy of immunotherapies in aged patients.

Yap and Taz are co-transcription factors that have been implicated in the development of many cancers. Here, we review the literature that analyzes the function of Yap/Taz in normal breast and breast cancer contexts. Our review of the literature suggests that Yap and Taz are involved in breast cancer and Taz, in particular, is involved in the triple-negative subtype. Nevertheless, the precise contexts in which Yap/Taz contribute to specific breast cancer phenotypes remains unclear. Indeed, Yap/Taz dysregulation acts differentially and in multiple epithelial cell types during early breast cancer progression. We propose Yap/Taz activation promotes breast cancer phenotypes in breast cancer precursor cells. Further, Yap dysregulation as a result of aging in breast tissue may result in microenvironments that increase the fitness of breast cancer precursor cells relative to the normal epithelia.

Do we really need another journal? Certainly, that was my initial reaction. Until I gave it some thought. Aging impacts everything about cancer, from incidence, to progression, to prognosis, to therapeutic options and their outcomes, to the psychosocial aspects of living with cancer. Note that 90% of cancers are diagnosed in those aged over 50 years.¹ Age is the dominant risk factor for both cancer incidence and mortality. Cancer is clearly a disease of aging. Historically, these links have been understudied and underappreciated, with aging mostly considered simply as the time to accumulate enough mutations to generate a cancer. Insufficient attention has been given to the aging-dependent changes in cells, tissues, immune function, and overall body fitness that influence the genesis and pathology of cancer, and outcomes for patients. But times are changing. There is increasing recognition of these connections in the research community and in funding agencies (in the United States, the National Institute of Cancer, the National Institute of Aging, and the Samuel Waxman Cancer Research Foundation have teamed up to fund research in this area, as well as workshops and focus groups). This interest is perhaps driven by the reality that the fraction of people on our planet above 65 years will double in the next few decades. Since most cancers occur in the elderly, we need to understand why and what we can do about it. The Silver Tsunami is upon us.

As the newest member of the Wiley family of scientific journals, Aging and Cancer will provide an important forum for new results and ideas that improve our understanding for how old age influences many different facets of cancer, from incidence, to its development and pathology, to treatment outcomes. Thus, the journal will span the aging and cancer field from basic biology (from computational modeling to molecular/cellular studies to model organisms to evolutionary biology), to clinical sciences (responses to therapy and outcomes research), to population health (cancer risk and survivorship). We will publish a variety of article types, from original research (including brief reports) to reviews and perspectives to editorials and white papers.

Links between old age and higher cancer incidence should be recognized for their fundamental importance in understanding biology in general. Following the early ideas of Medawar, Williams, Hamilton and more recently Kirkwood,^2-5 the 10 000 foot (evolutionary) explanation should be clear: there is minimal selection against diseases of old age, including cancers, beyond ages where contributions to future generations was likely (at least under “natural” conditions).⁶ Natural selection has tuned somatic maintenance programs to maximize reproductive output, and this maintenance wanes at older ages where reproduction becomes less likely. This physiological aging, which those