Testosterone treatment of aged male mice improves some but not all aspects of age-associated increases in influenza severity

Steeg, Landon G. vom; Attreed, Sarah E.; Zirkin, Barry R.; Klein, Sabra L.

doi:10.1016/j.cellimm.2019.103988

Cited by 12 publications

(11 citation statements)

References 58 publications

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“…Sex steroids, such as T, can have a significant influence on the function of inflammatory cells and regulation of the immune response. T has major effects on health and disease by altering metabolic, cardiovascular, and immune functions 54‐56 . T exerts mainly a suppressive role in immune functions, acting on the androgen receptors in immune cells regulating target gene expression 57 .…”

Section: Methodsmentioning

confidence: 99%

“…T has major effects on health and disease by altering metabolic, cardiovascular, and immune functions. [54][55][56] T exerts mainly a suppressive role in immune functions, acting on the androgen receptors in immune cells regulating target gene expression. 57 T suppresses immune cell activity by reducing inflammatory and promoting anti-inflammatory mediators' expression by macrophages and T cells, thus protecting against a variety of inflammation-mediated diseases.…”

Section: Immune System T and Agingmentioning

confidence: 99%

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Why does COVID‐19 kill more elderly men than women? Is there a role for testosterone?

Papadopoulos

Samplaski

2020

Andrology

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Background Recent epidemiological data indicate that there may be a gender predisposition to COVID‐19, with men predisposed to being most severely affected, and older men accounting for most deaths. Objectives Provide a review of the research literature, propose hypotheses and therapies based on the potential link between testosterone (T) and COVID‐19 induced mortality in elderly men. Materials and Methods A search of publications in academic electronic databases, and government and public health organization web sites on T, aging, inflammation, severe acute respiratory syndrome (SARS) due to coronavirus (CoV) 2 (SARS‐CoV‐2) infection, and COVID‐19 disease state and outcomes was performed. Results The link between T, the immune system and male aging is well‐established, as is the progressive decline in T levels with aging. In women, T levels drop before menopause and variably increase with advanced age. Elevated IL‐6 is a characteristic biomarker of patients infected with COVID‐19 and has been linked to the development of the acute respiratory distress syndrome (ARDS). Thus far, half of the admitted COVID‐19 patients developed ARDS, half of these patients died, and elderly male patients have been more likely to develop ARDS and die. Low T is associated with ARDS. These data suggest that low T levels may exacerbate the severity of COVID‐19 infection in elderly men. It may also stand to reason that normal T levels may offer some protection against COVID‐19. SARS‐CoV‐2 binds to the angiotensin‐converting enzyme 2, present in high levels in the testis. Conclusion At present, it is not known whether low T levels in aging hypogonadal males create a permissive environment for severe responses to COVID‐19 infection or if the virus inhibits androgen formation. Given the preponderance of COVID‐19 related mortality in elderly males, additional testing for gonadal function and treatment with T may be merited.

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Section: Methodsmentioning

confidence: 99%

Section: Immune System T and Agingmentioning

confidence: 99%

Why does COVID‐19 kill more elderly men than women? Is there a role for testosterone?

Papadopoulos

Samplaski

2020

Andrology

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“… 52 Sex steroids can have a crucial role on the function of inflammatory cells and regulation of the immune response. 53 In fact, it has been reported that they exert the following actions:…”

Section: Immune System In Covid-19 Infectionmentioning

confidence: 99%

Immune system and COVID-19 by sex differences and age

Ciarambino

Para

Giordano

2021

Womens Health (Lond Engl)

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In COVID-19 disease, are reported gender differences in relation to severity and death. The aim of this review is to highlight gender differences in the immune response to COVID-19. The included studies were identified using PubMed, until 30 October 2020. The search included the following keywords: SARS-CoV-2, COVID-19, gender, age, sex, and immune system. Literature described that females compared to males have greater inflammatory, antiviral, and humoral immune responses. In female, estrogen is a potential ally to alleviate SARS-COV-2 disease. In male, testosterone reduces vaccination response and depresses the cytokine response. In the older patients, and in particular, in female older patients, it has been reported a progressive functional decline in the immune systems. Differences by gender were reported in infection diseases, including SARS-CoV-2. These data should be confirmed by the other epidemiological studies.

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“… 9 In a limited capacity, aged mouse models have been used for infectious disease research as well. Especially in influenza infection, the aged mice have been used to test specific aspects of the pathogenesis, 12 test new therapeutics, 13 and test vaccines. 14 , 15 However, the aged animal model was not utilized for research on CDI until recently.…”

Section: Aging and CDImentioning

confidence: 99%

Teaching old mice new tricks: the utility of aged mouse models of C. difficile infection to study pathogenesis and rejuvenate immune response

2021

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Background Clostridioides difficile is a serious problem for the aging population. Aged mouse model of C. difficile infection (CDI) has emerged as a valuable tool to evaluate the mechanism of aging in CDI. Methods We reviewed five published studies utilizing aged mice (7–28 months) for CDI model for findings that may advance our understanding of how aging influences outcome from CDI. Results Aged mouse models of CDI uniformly demonstrated more severe disease in the old compared to young mice. Diminished neutrophil recruitment to intestinal tissue in aged mice is the most consistent finding. Differences in innate and humoral immune responses were also observed. The effects of aging on the outcome of infection were reversed by pharmacologic or microbiota-targeted interventions. Conclusion The aged mouse presents an important in vivo model to study CDI and elucidate the mechanisms underlying advanced age as an important risk factor for severe disease.

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Testosterone treatment of aged male mice improves some but not all aspects of age-associated increases in influenza severity

Cited by 12 publications

References 58 publications

Why does COVID‐19 kill more elderly men than women? Is there a role for testosterone?

Why does COVID‐19 kill more elderly men than women? Is there a role for testosterone?

Immune system and COVID-19 by sex differences and age

Teaching old mice new tricks: the utility of aged mouse models of C. difficile infection to study pathogenesis and rejuvenate immune response

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