Aging: Cancer – an unlikely couple

Aging: Cancer – an unlikely couple    

https://www.aging-us.com/issue/v9i9

At first glance, the molecular and cellular mechanisms governing aging and cancer appear to be completely distinct, even opposite in terms of their phenotypes. On one hand, aging represents a slow, often degenerative decline in cellular functions, while cancer cells are thought be “hyper-functional”. But are they really that opposite? It is no secret that aging increases one’s susceptibility to many diseases, including cancer. In fact, as aging populations throughout the world increase, there has been an unprecedented rise in cancer incidence and mortality. More than 50 percent of all cancers are diagnosed in patients 65 years or older [1]. There is now more than ever an urgent need to better understand the interplay between aging and cancer. This knowledge will undoubtedly improve clinical management of geriatric cancer patients. Here, we discuss some intriguing factors linking these two seemingly paradoxical conditions. There are several age-related epigenetic defects reminiscent of those commonly observed in cancer, suggesting a potential link between age-dependent biological changes and the concomitant increased cancer risk observed in the aged population. These include several global changes in the chromatin, altered gene expression, and overall genomic instability. For instance, certain site-specific hypermethylation events at promoters of genes involved in aging have also been reported as occurring during cancer. Notably, these include hypermethylation patterns at tumor-suppressor genes, such as suppressor of cytokine signaling 1 (SOCS1), hypermethylated in cancer 1 (HIC1), adenomatosis polyposis coli (APC), and a set of genes collectively termed the Polycomb group protein (PcG) target genes [2]. The resulting epigenetic silencing of these genes typically precedes many of the transformation events that give rise to cancer, further underscoring the idea that elucidating changes in the DNA methylome during aging may provide a powerful platform for better understanding the factors contributing to tumorigenesis. Aged-related changes in genomic imprinting constitute another aspect of epigenetic alterations in cancer. For instance, loss of imprinting (LOI) for the insulin growth factor 2 (IGF2) has been shown to be important in cancer progression. Fu et al demonstrated that increased IGF2 expression occurred as a result of selective LOI for IGF2 in the prostate of men during aging which was Editorial shown to be more extensive in men with age-associated prostate cancer [3]. In addition to epigenetic changes, senescence also stands out as an important link between aging and cancer. First described by Hayflick and Moorhead in 1961 [4], age-associated senescence denotes a cellautonomous state in which cells undergo irreversible cell cycle arrest marked by certain “Hayflick factors”, such as telomere loss, genomic instability, oxidative stress, and the accumulation of DNA damage [4]. Interestingly, many of these factors are intrinsic components of common age-related types of cancer, including breast, skin, and lung cancers [5]. Although senescence has been recognized to be a tumor suppressor mechanism due to its strong antiproliferative power, ironically, emerging evidence suggests that as the number of senescent cells increase with age, a more permissive tissue microenvironment develops which may, contribute significantly both to the initiation and progression of cancer. This is facilitated by a process that develops in advanced senescent cells known as the senescence-associated secretory phenotype (SASP) [6]. SASP is characterized by senescence-associated changes in which robust levels of cytokines, chemokines, and growth factors secreted into the surrounding microenvironment, acting on premalignant and tumor cells in a paracrine fashion, promoting a highly inflammatory state that enhances the invasive capabilities of these cells. Not surprisingly, this parallels a major pervasive feature of aging, i.e. a persistent state of chronic and systemic inflammation, which has been shown to exponentially increase the risk of cancer development. SASP is largely initiated by interleukin 1 alpha and beta (IL-1α and β), which serve as potent activators of important cancer signals, including the nuclear factor-κB (NF-κB) and p38 mitogen-activated protein kinase (p38MAPK) pathways. These pathways along with SASP can then serve to further activate a wide array of critical target gene products including those involved in epithelial-tomesenchyme transition (EMT) (eg. Metallomatrix proteins (MMPs), and metastasis (eg. MMPs, IL-6) of cancer cells [6]. 

When general population refer to modern medicine, accuracy plays one of the most significant roles and human lives are directly dependent on it. Hence, any researches related to medicine are necessary to meet the highest standards. The issue nowadays is that any results of researches can be published online and used as a reference without being adequately checked and approved. Mikhail (Misha) Blagosklonny of Oncotarget clearly understood this challenge and decided to come up with an alternative solution. That’s how a weekly oncology-focused research journal called “Oncotarget” has been established back in 2010. The main principle of this journal is related to Altmetric scores that are used as a quality indicator. That assists both readers and authors to quality-check publications with Altmetric Article Reports that generate “real-time feedback containing data summary related to a particular publication.” Oncotarget website has a full publications list with respective scores higher than 100 as well as reports mentioned above. Mikhail (Misha) Blagosklonny glad to share his new approach and hopes it provides the necessary assistance to anybody, who has interest in oncology.
Blagosklonny
“A diagnostic autoantibody signature for primary cutaneous melanoma” has the Altmetric score of 594. This study was published back in 2018 by Oncotarget and written by diversified experts from Hollywood Private Hospital, Edith Cowan University, Dermatology Specialist Group, St. John of God Hospital and The University of Western Australia. The introduction of the study mentions that “recent data shows that Australians are four times more likely to develop a cancer of the skin than any other type of cancer”, and shares an insight on melanoma that “is curable by surgical excision in the majority of cases, if detected at an early stage.”
The publication has got an Altmetric score of 594. Mikhail (Misha) Blagosklonny realizes that majority of readers are willing to comprehend the very meaning of it. Based on the Altmetric website, the score indicates “how many people have been exposed to and engaged with a scholarly output.” Likewise, the article about melanoma, was used for citations in various news articles 69 times. Moreover, it was referred to in 2 online blogs, as well as 25 Tweets on Twitter and 1 Facebook post. FOX23 of Tulsa, Oklahoma has headlined their report on July 20, 2018 as “New blood test could detect skin cancer early”, using the main content of Australia study
Another Oncotarget’s study with a top score of 476, is “Biomarkers for early diagnosis of malignant mesothelioma: Do we need another moon-shot,”. This research has appeared in 60 news stories, 1 online blog post and 6 Twitter posts. The majority of public may have seen a brief overview only, however those who visit Mikhail (Misha) Blagosklonny at Oncotarget, do get helpful scientific facts. Oncotarget is proud to have the ability to share with online readers this highly appreciated and top-quality information, that is trustworthy and reliable.
http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=18033