Regulation of aging and cancer by enhanced environmental activation of a hypothalamic-sympathoneural-adipocyte axis

Hassan, Quais N.; Queen, Nicholas J.; Cao, Lei

doi:10.21037/tcr.2020.02.39

Cited by 4 publications

(2 citation statements)

References 91 publications

(104 reference statements)

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“…Many cancers interact with the endocrine system and appear to have an especially strong relationship with obesity. There has been increasing attention to the relationship between cancer and leptin, which is abundant in adipose tissue (34)(35)(36). In fact, increased serum leptin levels have been reported to increase the risk of developing several cancers, including melanoma and colon cancer (37)(38)(39)(40).…”

Section: Discussionmentioning

confidence: 99%

An Enriched Environment Alters DNA Repair and Inflammatory Responses After Radiation Exposure

et al. 2021

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After the Fukushima Daiichi Nuclear Power Plant accident, there is growing concern about radiation-induced carcinogenesis. In addition, living in a long-term shelter or temporary housing due to disasters might cause unpleasant stress, which adversely affects physical and mental health. It’s been experimentally demonstrated that “eustress”, which is rich and comfortable, has beneficial effects for health using mouse models. In a previous study, mice raised in the enriched environment (EE) has shown effects such as suppression of tumor growth and enhancement of drug sensitivity during cancer treatment. However, it’s not yet been evaluated whether EE affects radiation-induced carcinogenesis. Therefore, to evaluate whether EE suppresses a radiation-induced carcinogenesis after radiation exposure, in this study, we assessed the serum leptin levels, radiation-induced DNA damage response and inflammatory response using the mouse model. In brief, serum and tissues were collected and analyzed over time in irradiated mice after manipulating the raising environment during the juvenile or adult stage. To assess the radiation-induced DNA damage response, we performed immunostaining for phosphorylated H2AX which is a marker of DNA double-strand break. Focusing on the polarization of macrophages in the inflammatory reaction that has an important role in carcinogenesis, we performed analysis using tissue immunofluorescence staining and RT-qPCR. Our data confirmed that EE breeding before radiation exposure improved the responsiveness to radiation-induced DNA damage and basal immunity, further suppressing the chronic inflammatory response, and that might lead to a reduction of the risk of radiation-induced carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

An Enriched Environment Alters DNA Repair and Inflammatory Responses After Radiation Exposure

et al. 2021

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“…The article by Muss, Smitherman, Wood et al , provides an assessment of P 16 as a marker of biological aging ( 20 ). Hassan, Queen, and Cao, detail the impact of enhanced environment on cancer development and its mediation by a hypothalamic-sympathoneural-adipocyte axis ( 21 ). Xu and Rogers, address immune regulation of cancer and how it is impacted by physical activity and energy restriction ( 22 ).…”

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confidence: 99%

Apocalyptic horsemen of geriatric oncology

Berger¹

2020

Transl Cancer Res TCR

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Apocalyptic horsemen of geriatric oncologyConsidering the processes we encounter and must overcome to reduce the burden of Geriatric Oncology, I am reminded of the scriptural description of the Four Horsemen of the Apocalypse, War, Pestilence, Famine, and Death. All are synergistic and portend devastating outcomes. The Apocalyptic Horsemen that we must engage and thwart in Geriatric Oncology, include Genomic Infidelity, Cellular Senescence, Inflammaging and Diabesity.Genomic Infidelity, including DNA mutagenesis, rearrangement and epigenetic changes, continuously increases over the lifespan. It provides the enabling, disruptive background for almost all malignant transformation (1,2). These processes essentially throw the switches that result in oncogene activation and inactivation of tumor suppressor genes. While extensive DNA Damage Response Pathways and Epigenetic Regulatory Systems exist to counteract these changes, their inexorable progression leads to cancer as a common disease of older adults (3).Cellular senescence, which may be associated with mutagenesis, as well as with cumulative environmental influences, leads to a number of age-associated phenotypes that significantly impact geriatric oncology. These include immuno-senescence, myo-senescence, sarcopenia, and the senescence associated secretory phenotype (SASP). Immuno-senescence results in loss and/or alterations in the immune system that may contribute to age-associated declines in immuno surveillance leading to a permissive milieu for tumor growth and increased susceptibility to infectious organisms. Senescence of muscle satellite cells accompanied by inadequate nutrition and physical activity, may contribute to decreases in skeletal muscle mass resulting in age-associated sarcopenia (4). The latter can lead to frailty, falls, functional decline, and death (5). At the same time, sarcopenia can interfere with patient tolerability of cancer therapies ( 6). Yet another consequence of senescence is the SASP, in which cells lose their proliferative capacity, and increase their secretion of inflammatory cytokines, many of which may amplify tumor growth supportive factors in the tumor microenvironment (7-9).Inflammaging has been identified as age-associated chronic, sterile, low-grade inflammation that occurs in response to endogenous cell debris and metabolic errors. It may particularly occur in pathways that mediate gut-liver, gut-brain, and/or gutadipose tissue communication and interactions (10). Unlike classic acute inflammation, which is usually targeted at destroying foreign pathogenic organisms, and then terminates once the pathogens are eliminated, inflammaging is low-grade and ongoing (11). Consequences, of inflammaging include synthesis and release of cytokines including TNF, IL-1, IL-6, and IL-8, as well as epigenetic changes leading to accelerated biological aging as demonstrated by altered patterns of DNA methylation (10).Diabesity denotes the expanding worldwide prevalence of obesity, its association with increased incidence of diabetes an...

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Environmental Enrichment Mitigates Age-Related Metabolic Decline and Lewis Lung Carcinoma Growth in Aged Female Mice

Queen

Deng

Huang

et al. 2021

Cancer Prevention Research

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Aging is a complex physiological process that leads to the progressive decline of metabolic and immune function, among other biological mechanisms. As global life expectancy increases, it is important to understand determinants of healthy aging—including environmental and genetic factors—and thus slow the onset or progression of age-related disease. Environmental enrichment (EE) is a housing environment wherein laboratory animals engage with complex physical and social stimulation. EE is a prime model to understand environmental influences on aging dynamics, as it confers an antiobesity and anticancer phenotype that has been implicated in healthy aging and health span extension. Although EE is frequently used to study malignancies in young mice, fewer studies characterize EE-cancer outcomes in older mice. Here, we used young (3-month-old) and aged (14-month-old) female C57BL/6 mice to determine whether EE would be able to mitigate age-related deficiencies in metabolic function and thus alter Lewis lung carcinoma (LLC) growth. Overall, EE improved metabolic function, resulting in reduced fat mass, increased lean mass, and improved glycemic processing; many of these effects were stronger in the aged cohort than in the young cohort, indicating an age-driven effect on metabolic responses. In the aged-EE cohort, subcutaneously implanted LLC tumor growth was inhibited and tumors exhibited alterations in various markers of apoptosis, proliferation, angiogenesis, inflammation, and malignancy. These results validate EE as an anticancer model in aged mice and underscore the importance of understanding environmental influences on cancer malignancy in aged populations. Prevention Relevance: Environmental enrichment (EE) serves as a model of complex physical and social stimulation. This study validates EE as an anticancer intervention paradigm in aged mice and underscores the importance of understanding environmental influences on cancer malignancy in aged populations.

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Regulation of aging and cancer by enhanced environmental activation of a hypothalamic-sympathoneural-adipocyte axis

Cited by 4 publications

References 91 publications

An Enriched Environment Alters DNA Repair and Inflammatory Responses After Radiation Exposure

An Enriched Environment Alters DNA Repair and Inflammatory Responses After Radiation Exposure

Apocalyptic horsemen of geriatric oncology

Environmental Enrichment Mitigates Age-Related Metabolic Decline and Lewis Lung Carcinoma Growth in Aged Female Mice

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