Premature aging in behavior and immune functions in tyrosine hydroxylase haploinsufficient female mice. A longitudinal study

Garrido, António; Cruces, Julia; Ceprián, Noemí; Hernández‐Sánchez, Catalina; Fuente, Mónica De la

doi:10.1016/j.bbi.2018.01.003

Cited by 18 publications

(24 citation statements)

References 126 publications

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“…Apparently, the key phenomenon are the oxidative and inflammatory stresses, which, not without reason, are associated with several non-communicable chronic diseases prevalent among the elderly (44,46). In fact, spleen and thymus cells from prematurely immunosenescent mice models have decreased antioxidant defenses and significantly increased oxidants and pro-inflammatory cytokines production (44)(45)(46). Interestingly, the antioxidant vs. oxidant imbalance observed in prematurely immunosenescent mice was similar to the one observed in old wild-type animals (44,47).…”

Section: Innate Immune Response and Inflamm-agingmentioning

confidence: 84%

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Remodeling of the Immune Response With Aging: Immunosenescence and Its Potential Impact on COVID-19 Immune Response

et al. 2020

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Elderly individuals are the most susceptible to an aggressive form of coronavirus disease (COVID-19), caused by SARS-CoV-2. The remodeling of immune response that is observed among the elderly could explain, at least in part, the age gradient in lethality of COVID-19. In this review, we will discuss the phenomenon of immunosenescence, which entails changes that occur in both innate and adaptive immunity with aging. Furthermore, we will discuss inflamm-aging, a low-grade inflammatory state triggered by continuous antigenic stimulation, which may ultimately increase all-cause mortality. In general, the elderly are less capable of responding to neo-antigens, because of lower naïve T cell frequency. Furthermore, they have an expansion of memory T cells with a shrinkage of the T cell diversity repertoire. When infected by SARS-CoV-2, young people present with a milder disease as they frequently clear the virus through an efficient adaptive immune response. Indeed, antibody-secreting cells and follicular helper T cells are thought to be effectively activated in young patients that present a favorable prognosis. In contrast, the elderly are more prone to an uncontrolled activation of innate immune response that leads to cytokine release syndrome and tissue damage. The failure to trigger an effective adaptive immune response in combination with a higher pro-inflammatory tonus may explain why the elderly do not appropriately control viral replication and the potential clinical consequences triggered by a cytokine storm, endothelial injury, and disseminated organ injury. Enhancing the efficacy of the adaptive immune response may be an important issue both for infection resolution as well as for the appropriate generation of immunity upon vaccination, while inhibiting inflamm-aging will likely emerge as a potential complementary therapeutic approach in the management of patients with severe COVID-19.

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Section: Innate Immune Response and Inflamm-agingmentioning

confidence: 84%

“…The mice model of premature immunosenescence was refined and new models were developed as well (44,45). Apparently, the key phenomenon are the oxidative and inflammatory stresses, which, not without reason, are associated with several non-communicable chronic diseases prevalent among the elderly (44,46).…”

Section: Innate Immune Response and Inflamm-agingmentioning

confidence: 99%

Remodeling of the Immune Response With Aging: Immunosenescence and Its Potential Impact on COVID-19 Immune Response

et al. 2020

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“…The results showed that these numbers were lower ( p < 0.001) in PAM and TH-HZ than in NPAM and WT, respectively, and were similar to those in cells from old animals. In the case of the results of basal lymphoproliferation, immune function that is increased with age due to chronic low-inflammation appearance [18,19,20,30,31,32,33,34,35,36,37,38,39,40,41], the c.p.m. in leukocytes from PAM and TH-HZ were higher ( p < 0.001) than those in the corresponding controls (NPAM and WT, respectively).…”

Section: Resultsmentioning

confidence: 99%

“…These resulted in a shorter mean lifespan than that of the corresponding non-prematurely aging mice (NPAM) of the same sex and age [10,33,34]. In addition, female mice with the deletion of a single allele (hemi-zygotic: HZ) of the tyrosine hydroxylase ( th ) gene (TH-HZ), and with the consequent lower catecholamine content, even in their immune cells, presented a premature immunosenescence in their peritoneal leukocytes, exhibiting higher oxidative stress in these cells and having a lower mean lifespan in comparison to wild type (WT) mice [35]. However, whether these PAM and TH-HZ mice, at adult age, would show oxi-inflamm-aging in these leukocytes and those from other immunological organs, such as spleen and thymus, and whether they exhibited in their immune cells a pattern of functions and redox state with similar values to those observed in chronologically old mice, are aspects that have not been studied yet.…”

Section: Introductionmentioning

confidence: 99%

Oxidative-Inflammatory Stress in Immune Cells from Adult Mice with Premature Aging

Garrido

Cruces

Ceprián

et al. 2019

IJMS

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Oxidative and inflammatory stresses are closely related processes, which contribute to age-associated impairments that affect the regulatory systems such as the immune system and its immunosenescence. Therefore, the aim of this work was to confirm whether an oxidative/inflammatory stress occurs in immune cells from adult mice with premature aging, similar to that shown in leukocytes from chronologically old animals, and if this results in immunosenescence. Several oxidants/antioxidants and inflammatory/anti-inflammatory cytokines were analyzed in peritoneal leukocytes from adult female CD1 mice in two models of premature aging—(a) prematurely aging mice (PAM) and (b) mice with the deletion of a single allele (hemi-zygotic: HZ) of the tyrosine hydroxylase (th) gene (TH-HZ), together with cells from chronologically old animals. Several immune function parameters were also studied in peritoneal phagocytes and lymphocytes. The same oxidants and antioxidants were also analyzed in spleen and thymus leukocytes. The results showed that the immune cells of PAM and TH-HZ mice presented lower values of antioxidant defenses and higher values of oxidants/pro-inflammatory cytokines than cells from corresponding controls, and similar to those in cells from old animals. Moreover, premature immunosenescence in peritoneal leukocytes from both PAM and TH-HZ mice was also observed. In conclusion, adult PAM and TH-HZ mice showed oxidative stress in their immune cells, which would explain their immunosenescence.

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“…Female mice with haploinsufficiency (hemizygous; HZ) of the tyrosine hydroxylase (TH) enzyme, responsible of catecholamine production, show premature deterioration of sensorimotor abilities and exploratory capacity together with lower immunological responses and higher oxi-inflamm-aging parameters than their wild type littermates. The increased XOR activity in mouse peritoneal leukocyte lysate contributes to oxidative stress and early aging, which reduce their lifespan [75].…”

Section: Animal Studiesmentioning

confidence: 99%

Pro-Aging Effects of Xanthine Oxidoreductase Products

et al. 2020

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The senescence process is the result of a series of factors that start from the genetic constitution interacting with epigenetic modifications induced by endogenous and environmental causes and that lead to a progressive deterioration at the cellular and functional levels. One of the main causes of aging is oxidative stress deriving from the imbalance between the production of reactive oxygen (ROS) and nitrogen (RNS) species and their scavenging through antioxidants. Xanthine oxidoreductase (XOR) activities produce uric acid, as well as reactive oxygen and nitrogen species, which all may be relevant to such equilibrium. This review analyzes XOR activity through in vitro experiments, animal studies and clinical reports, which highlight the pro-aging effects of XOR products. However, XOR activity contributes to a regular level of ROS and RNS, which appears essential for the proper functioning of many physiological pathways. This discourages the use of therapies with XOR inhibitors, unless symptomatic hyperuricemia is present.

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Premature aging in behavior and immune functions in tyrosine hydroxylase haploinsufficient female mice. A longitudinal study

Cited by 18 publications

References 126 publications

Remodeling of the Immune Response With Aging: Immunosenescence and Its Potential Impact on COVID-19 Immune Response

Remodeling of the Immune Response With Aging: Immunosenescence and Its Potential Impact on COVID-19 Immune Response

Oxidative-Inflammatory Stress in Immune Cells from Adult Mice with Premature Aging

Pro-Aging Effects of Xanthine Oxidoreductase Products

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