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Noemí Ceprián

Bio: Noemí Ceprián is an academic researcher from Complutense University of Madrid. The author has contributed to research in topics: Immunosenescence & Medicine. The author has an hindex of 4, co-authored 11 publications receiving 63 citations.

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Journal ArticleDOI
TL;DR: Several aspects that characterize CKD-associated CVDs, such as etiopathogenic elements that CKD patients share with the general population, changes in the cellular balance of reactive oxygen species (ROS), and the associated process of cellular senescence are discussed.
Abstract: Cardiovascular diseases (CVDs), especially those involving a systemic inflammatory process such as atherosclerosis, remain the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). CKD is a systemic condition affecting approximately 10% of the general population. The prevalence of CKD has increased over the past decades because of the aging of the population worldwide. Indeed, CVDs in patients with CKD constitute a premature form of CVD observed in the general population. Multiple studies indicate that patients with renal disease undergo accelerated aging, which precipitates the appearance of pathologies, including CVDs, usually associated with advanced age. In this review, we discuss several aspects that characterize CKD-associated CVDs, such as etiopathogenic elements that CKD patients share with the general population, changes in the cellular balance of reactive oxygen species (ROS), and the associated process of cellular senescence. Uremia-associated aging is linked with numerous changes at the cellular and molecular level. These changes are similar to those observed in the normal process of physiologic aging. We also discuss new perspectives in the study of CKD-associated CVDs and epigenetic alterations in intercellular signaling, mediated by microRNAs and/or extracellular vesicles (EVs), which promote vascular damage and subsequent development of CVD. Understanding the processes and factors involved in accelerated senescence and other abnormal intercellular signaling will identify new therapeutic targets and lead to improved methods of diagnosis and monitoring for patients with CKD-associated CVDs.

64 citations

Journal ArticleDOI
TL;DR: Adult PAM and TH-HZ mice showed oxidative stress in their immune cells, which would explain their immunosenescence.
Abstract: 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.

34 citations

Journal ArticleDOI
01 Nov 2021-Cells
TL;DR: In this article, the function of immune cells can be used as an indicator of the rate of aging of an individual, and the immune system can work as a driver of aging by amplifying the oxidative-inflammatory stress associated with aging (oxi-inflamm-aging).
Abstract: Aging is the result of the deterioration of the homeostatic systems (nervous, endocrine, and immune systems), which preserve the organism’s health. We propose that the age-related impairment of these systems is due to the establishment of a chronic oxidative stress situation that leads to low-grade chronic inflammation throughout the immune system’s activity. It is known that the immune system weakens with age, which increases morbidity and mortality. In this context, we describe how the function of immune cells can be used as an indicator of the rate of aging of an individual. In addition to this passive role as a marker, we describe how the immune system can work as a driver of aging by amplifying the oxidative-inflammatory stress associated with aging (oxi-inflamm-aging) and inducing senescence in far tissue cells. Further supporting our theory, we discuss how certain lifestyle conditions (such as social environment, nutrition, or exercise) can have an impact on longevity by affecting the oxidative and inflammatory state of immune cells, regulating immunosenescence and its contribution to oxi-inflamm-aging.

34 citations

Journal ArticleDOI
TL;DR: Haploinsufficiency of th gene in female mice appears to provoke premature aging of the regulatory systems affecting mean lifespan, and adult TH-HZ mice presented worse sensorimotor abilities and exploratory capacity than their WT littermates as well as greater anxiety-like behaviors.
Abstract: Aging is accompanied by impairment in the nervous, immune, and endocrine systems as well as in neuroimmunoendocrine communication. In this context, there is an age-related alteration of the physiological response to acute stress, which is modulated by catecholamine (CA), final products of the sympathetic-adreno-medullary axis. The involvement of CA in essential functions of the nervous system is consistent with the neuropsychological deficits found in mice with haploinsufficiency (hemizygous; HZ) of tyrosine hydroxylase (TH) enzyme (TH-HZ). However, other possible alterations in regulatory systems have not been studied in these animals. The aim of the present work was to analyze whether adult TH-HZ female mice presented the impairment of behavioral traits and immunological responses that occurs with aging and whether they had affected their mean lifespan. ICR-CD1 female TH-HZ and wild type (WT) mice were used in a longitudinal study. Behavioral tests were performed on adult and old mice in order to evaluate their sensorimotor abilities and exploratory capacity, as well as anxiety-like behaviors. At the ages of 2 ± 1, 4 ± 1, 9 ± 1, 13 ± 1 and 20 ± 1 months, peritoneal leukocytes were extracted and several immune functions were assessed (phagocytic capacity, Natural Killer (NK) cytotoxicity, and lymphoproliferative response to lipopolysaccharide (LPS) and concanavalin A (ConA)). In addition, several oxidative stress parameters (catalase, glutathione reductase and glutathione peroxidase activities, and reduced glutathione (GSH) concentrations as antioxidant compounds as well as xanthine oxidase activity, oxidized glutathione (GSSG) concentrations, and GSSG/GSH ratio as oxidants) were analyzed. As inflammatory stress parameters TNF-alpha and IL-10 concentrations, and TNF-alpha/IL-10 ratios as inflammatory/anti-inflammatory markers, were measured. Animals were maintained in standard conditions until their natural death. The results indicate that adult TH-HZ mice presented worse sensorimotor abilities and exploratory capacity than their WT littermates as well as greater anxiety-like behaviors. With regards to the immune system, adult TH-HZ animals exhibited lower values of phagocytic capacity, NK cytotoxicity, and lymphoproliferative response to LPS and ConA than WT mice. Moreover, immune cells of TH-HZ mice showed higher oxidative and inflammatory stress than those of WT animals. Although these differences between TH-HZ and WT, in general, decreased with aging, this premature immunosenescence and impairment of behavior of TH-HZ mice was accompanied by a shorter mean lifespan in comparison to WT counterparts. In conclusion, haploinsufficiency of th gene in female mice appears to provoke premature aging of the regulatory systems affecting mean lifespan.

20 citations

Journal ArticleDOI
TL;DR: The results showed that old animals, after cohabitation with adult mice, presented an improvement of behavioral capacities, immune functions, and a lower oxidative and inflammatory stress, and they exhibited a higher life span.
Abstract: The social environment can affect the regulatory systems, and cohabitation with sick subjects is a negative factor for the nervous and immune systems, compromising the life span. Nevertheless, the possible beneficial effects of a positive social environment on nervous and immune functions and longevity have not yet been studied. The aim of this study was to analyze several behavioral and immune function parameters and life span in old mice after their cohabitation with adult animals. Old and adult ICR-CD1 female mice were divided into three experimental groups: adult controls, old controls, and a social environment experimental group. The latter contained two old mice with five adult mice. After 2 months in these conditions, mice were submitted to a behavioral battery of tests to analyze their sensorimotor abilities, anxiety-like behaviors, and exploratory capacities. Peritoneal leukocytes were then collected, and several immune functions as well as oxidative and inflammatory stress parameters were assessed. The animals were maintained in the same conditions until natural death occurred. The results showed that old animals, after cohabitation with adult mice, presented an improvement of behavioral capacities, immune functions, and a lower oxidative and inflammatory stress. Consequently, they exhibited a higher life span.

18 citations


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392 citations

Journal ArticleDOI
TL;DR: The aim of the present review was to summarize experimental data and clinical observations that linked the pathophysiology mechanisms of “inflamm-aging”, mild-grade inflammation, and cytokine storm in some elderly adults with severe COVID-19 infection.
Abstract: Novel Coronavirus disease 2019 (COVID-19), is an acute respiratory distress syndrome (ARDS), which is emerged in Wuhan, and recently become worldwide pandemic. Strangely, ample evidences have been shown that the severity of COVID-19 infections varies widely from children (asymptomatic), adults (mild infection), as well as elderly adults (deadly critical). It has proven that COVID-19 infection in some elderly critical adults leads to a cytokine storm, which is characterized by severe systemic elevation of several pro-inflammatory cytokines. Then, a cytokine storm can induce edematous, ARDS, pneumonia, as well as multiple organ failure in aged patients. It is far from clear till now why cytokine storm induces in only COVID-19 elderly patients, and not in young patients. However, it seems that aging is associated with mild elevated levels of local and systemic pro-inflammatory cytokines, which is characterized by “inflamm-aging”. It is highly likely that “inflamm-aging” is correlated to increased risk of a cytokine storm in some critical elderly patients with COVID-19 infection. A systematic search in the literature was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, as well as Google Scholar pre-print database using all available MeSH terms for COVID-19, Coronavirus, SARS-CoV-2, senescent cell, cytokine storm, inflame-aging, ACE2 receptor, autophagy, and Vitamin D. Electronic database searches combined and duplicates were removed. The aim of the present review was to summarize experimental data and clinical observations that linked the pathophysiology mechanisms of “inflamm-aging”, mild-grade inflammation, and cytokine storm in some elderly adults with severe COVID-19 infection.

201 citations

Journal ArticleDOI
TL;DR: The phenomenon of immunosenescence, which entails changes that occur in both innate and adaptive immunity with aging, is discussed, and inflamm-aging, a low-grade inflammatory state triggered by continuous antigenic stimulation, which may ultimately increase all-cause mortality is discussed.
Abstract: 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 naive 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.

156 citations

Journal ArticleDOI
TL;DR: Genetic as well as pharmacological models with senolysis contributed to reverse aging phenotypes and ameliorated pathologies in age-related disorders without enhancing the risk of tumorigenesis, and opened a new avenue for aging research.

97 citations

Journal ArticleDOI
TL;DR: A range of senotherapeutic strategies have been developed to directly or indirectly influence Klotho expression, with varying degrees of success, and all have significant potential to mitigate loss of physiological function and resilience accompanying old age and to improve outcomes within the diseasome of aging.
Abstract: Klotho has been recognized as a gene involved in the aging process in mammals for over 30 years, where it regulates phosphate homeostasis and the activity of members of the fibroblast growth factor (FGF) family. The α-Klotho protein is the receptor for Fibroblast Growth Factor-23 (FGF23), regulating phosphate homeostasis and vitamin D metabolism. Phosphate toxicity is a hallmark of mammalian aging and correlates with diminution of Klotho levels with increasing age. As such, modulation of Klotho activity is an attractive target for therapeutic intervention in the diseasome of aging; in particular for chronic kidney disease (CKD), where Klotho has been implicated directly in the pathophysiology. A range of senotherapeutic strategies have been developed to directly or indirectly influence Klotho expression, with varying degrees of success. These include administration of exogenous Klotho, synthetic and natural Klotho agonists and indirect approaches, via modulation of the foodome and the gut microbiota. All these approaches have significant potential to mitigate loss of physiological function and resilience accompanying old age and to improve outcomes within the diseasome of aging.

82 citations