Centenarians and COVID-19: Is There a Link between Longevity and Better Immune Defense?
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ABSTRACT:
SUBMITTER: Kordowitzki P
PROVIDER: S-EPMC8450859 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAlthough it is known that mortality due to COVID-19 increases progressively with age, the probability of dying from this serious infection among the oldest-old population is little known, and controversial data are found in literature.MethodsWe examine the mortality by year and month of birth of Belgians who had turned 100 during the current COVID-19 pandemic and whose birth fell on the years around the end the First World War and the outbreak of the H1N1 "Spanish flu" pandemic.FindingsThe COVID-19 mortality of the "older" centenarians is significantly lower than that of "younger" centenarians, and this difference between the two groups reaches a maximum on August 1, 1918 as the discriminating cut-off date of birth. Having excluded the plausible impact of the end of WWI it becomes clear that this date corresponds to the time of reporting the first victims of the Spanish flu pandemic in Belgium.InterpretationIn this study, the striking temporal coincidence between the outbreak of the Spanish flu epidemic and the birth of the cohorts characterized by greater fragility towards COVID-19 in 2020 strongly suggests a link between exposure to 1918 H1N1 pandemic influenza and resistance towards 2020 SARS-Cov-2. It can be speculated that the lifetime persistence of cross-reactive immune mechanisms has enabled centenarians exposed to the Spanish flu to overcome the threat of COVID-19 a century later.
| S-EPMC8507269 | biostudies-literature
Project description:We have shown before that at least one intracellular proteolytic system seems to be at least as abundant in the peripheral blood lymphocytes of centenarians as in the same cells of young individuals (with the cells of the elderly population showing a significant dip compared to both young and centenarian cohorts). Despite scarce published data, in this review, we tried to answer the question how do different types of cells of longevous people-nonagenarians to (semi)supercentenarians-maintain the quality and quantity of their structural and functional proteins? Specifically, we asked if more robust proteodynamics participate in longevity. We hypothesized that at least some factors controlling the maintenance of cellular proteomes in centenarians will remain at the "young" level (just performing better than in the average elderly). In our quest, we considered multiple aspects of cellular protein maintenance (proteodynamics), including the quality of transcribed DNA, its epigenetic changes, fidelity and quantitative features of transcription of both mRNA and noncoding RNAs, the process of translation, posttranslational modifications leading to maturation and functionalization of nascent proteins, and, finally, multiple facets of the process of elimination of misfolded, aggregated, and otherwise dysfunctional proteins (autophagy). We also included the status of mitochondria, especially production of ATP necessary for protein synthesis and maintenance. We found that with the exception of the latter and of chaperone function, practically all of the considered aspects did show better performance in centenarians than in the average elderly, and most of them approached the levels/activities seen in the cells of young individuals.
| S-EPMC9918038 | biostudies-literature
Project description:IntroductionObesity is commonly reported in COVID-19 patients and is associated with poorer outcomes. It is suggested that leptin could be the missing link between obesity and severe COVID-19. Our study aimed to unravel the link between adipokines, COVID-19 status, immune response, and outcomes in severe pneumonia.MethodsIn this prospective observational single-center study, 63 immunocompetent patients with severe pneumonia (36 non-COVID-19 and 27 COVID-19) were enrolled, most required intensive care. Clinical and biological characteristics (glucose metabolism, plasma adipokines, and cytokine concentrations) and outcomes were compared.ResultsAt similar baseline severity, COVID-19 patients required mechanical ventilation for significantly longer than non-COVID-19 patients (p = 0.0049). Plasma concentrations of leptin and adiponectin were respectively positively and negatively correlated with BMI and glucose metabolism (glycemia and insulinemia), but not significantly different between the two groups. Leptin levels were negatively correlated with IL-1β and IL-6, but the adipokines were not correlated with most other inflammatory mediators, baseline severity (SOFA score), or the duration of mechanical ventilation.ConclusionAdipokine levels were correlated with BMI but not with most inflammatory mediators, severity, or outcomes in severe pneumonia, regardless of the origin. The link between obesity, dysregulated immune response, and life-threatening COVID-19 requires further investigation.Clinical trialClinicalTrials.gov: NCT03505281.
| S-EPMC8166380 | biostudies-literature
Project description:Centenarians, who show mild infections and low incidence of tumors, are the optimal model to investigate healthy aging. However, longevity related immune characteristics has not been fully revealed largely due to lack of appropriate controls. In this study, single-cell transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) derived from seven centenarians (CEN), six centenarians' offspring (CO), and nine offspring spouses or neighbors (Control, age-matched to CO) are performed to investigate the shared immune features between CEN and CO. The results indicate that among all 12 T cell clusters, the cytotoxic-phenotype-clusters (CPC) and the naïve-phenotype-clusters (NPC) significantly change between CEN and ontrol. Compared to Control, both CEN and CO are characterized by depleted NPC and increased CPC, which is dominated by CD8+ T cells. Furthermore, CPC from CEN and CO share enhanced signaling pathways and transcriptional factors associated with immune response, and possesse similar T-cell-receptor features, such as high clonal expansion. Interestingly, rather than a significant increase in GZMK+ CD8 cells during aging, centenarians show accumulation of GZMB+ and CMC1+ CD8 T cells. Collectively, this study unveils an immune remodeling pattern reflected by both quantitative increase and functional reinforcement of cytotoxic T cells which are essential for healthy aging.
| S-EPMC9799020 | biostudies-literature
Project description:BackgroundCentenarians are known to be successful agers compared to other older adults.ObjectiveThe objective of the present study was to compare coronavirus disease (COVID-19) symptoms and outcomes in centenarians and other residents living in nursing homes. Design-Setting-Subjects-Methods: A retrospective multicenter cohort study was conducted using data from 15 nursing homes in the Marseille area. Older residents with confirmed COVID-19 between March and June 2020 were enrolled. The clinical and biological characteristics, the treatment measures, and the outcomes in residents living in these nursing homes were collected from the medical records.ResultsA total of 321 residents were diagnosed with COVID-19 including 12 centenarians. The median age was 101 years in centenarians and 89 years in other residents. The most common symptoms were asthenia and fever. Three centenarians (25%) experienced a worsening of pre-existing depression (vs. 5.5% of younger residents; p = 0.032). Mortality was significantly higher in centenarians than in younger residents (50% vs. 21.3%, respectively; p = 0.031). A quarter of the younger residents and only one centenarian were hospitalized. However, 33.3% of the centenarians received treatment within the context of home hospitalization.ConclusionWorsening of pre-existing depression seems to be more frequent in centenarians with COVID-19 in nursing homes. This population had a higher mortality rate but a lower hospitalization rate than younger residents.
| S-EPMC7993710 | biostudies-literature
Project description:Several countries around the world have faced an important obesity challenge for the past four decades as the result of an obesogenic environment. This disease has a multifactorial origin and it is associated with multiple comorbidities including type 2 diabetes, hypertension, osteoarthritis, metabolic syndrome, cancer, and dyslipidemia. With regard to dyslipidemia, hypertriglyceridemia is a well-known activator of the NLRP3 inflammasome, triggering adipokines and cytokines secretion which in addition induce a systemic inflammatory state that provides an adequate scenario for infections, particularly those mediated by viruses such as HIV, H1N1 influenza, and SARS-CoV-2. The SARS-CoV-2 infection causes the coronavirus disease 2019 (COVID-19) and it is responsible for the pandemic that we are currently living. COVID-19 causes an aggressive immune response known as cytokine release syndrome or cytokine storm that causes multiorgan failure and in most cases leads to death. In the present work, we aimed to review the molecular mechanisms by which obesity-associated systemic inflammation could cause a more severe clinical presentation of COVID-19. The SARS-CoV-2 infection could potentiate or accelerate the pre-existing systemic inflammatory state of individuals with obesity, via the NLRP3 inflammasome activation and the release of pro-inflammatory cytokines from cells trough Gasdermin-pores commonly found in cell death by pyroptosis.
| S-EPMC7662564 | biostudies-literature
Project description: Not available
| S-EPMC11210044 | biostudies-literature
Project description:The 11p15.5 chromosomal region (2.8 Mb) is of particular interest as it encloses five genes (HRAS1, SIRT3, TH, INS and IGF2), the variability of which was found to be associated with life extension by association studies. Mostly important, the above genes are homologous of genes that modulate lifespan in model organisms. We scanned the area in four European sample groups for a total of 1321 centenarians and 1140 younger subjects, who shared with centenarians ethnicity and geographical origin, with a set of 239 SNPs. No significant results (P<0.05) have been found on the earlier associated loci (ie, TH, IGF2, INS and HRAS1), and this study could not confirm the earlier findings on each of those genes. A meta-analysis was carried out on the SIRT3 SNP data; a total number of 2461 samples were included, but no positive association was found except for one SNP having a significant effect (rs939915). The same meta-analysis approach has been applied to the other 229 markers, and six SNPs have been found significant for the frequent genotype (rs4073591, DEAF1-rs4073590, KRTAP5-6-rs11040489, rs4930001, TSPAN32-rs800140 and rs16928120). This experience, although unable to confirm the earlier findings of the literature, highlights all the common difficulties of such studies in human longevity. Despite the rather negative findings presented here, the results derived from unprecedented studies involving such a large number of centenarians should be disseminated, thus contributing to set up adequate strategies to disentangle complex and likely heterogeneous phenotypes.
| S-EPMC2986679 | biostudies-literature
Project description:In this prospective observational cohort study, we found transcriptional evidence that persistent immune dysfunction was associated with 28-day mortality in both COVID-19 and non-COVID-19 septic patients. COVID-19 patients had an early antiviral response but became indistinguishable on a gene expression level from non-COVID-19 sepsis patients a week later. Early treatment of COVID-19 and non-COVID-19 sepsis ICU patients should focus on pathogen control, but both patient groups also require novel immunomodulatory treatments, particularly later during ICU hospitalization, independent of admission diagnosis. Some T1 samples were uploaded in GSE185263 and were not re-uploaded in this series.
2023-03-24 | GSE222393 | GEO
Project description:The demographic and social changes of the past decades have determined improvements in public health and longevity. So, the number of centenarians is increasing as a worldwide phenomenon. Scientists have focused their attention on centenarians as optimal model to address the biological mechanisms of "successful and unsuccessful ageing". They are equipped to reach the extreme limits of human life span and, most importantly, to show relatively good health, being able to perform their routine daily life and to escape fatal age-related diseases, such as cardiovascular diseases and cancer. Thus, particular attention has been centered on their genetic background and immune system. In this review, we report our data gathered for over 10 years in Sicilian centenarians. Based on results obtained, we suggest longevity as the result of an optimal performance of immune system and an over-expression of anti-inflammatory sequence variants of immune/inflammatory genes. However, as well known, genetic, epigenetic, stochastic and environmental factors seem to have a crucial role in ageing and longevity. Epigenetics is associated with ageing, as demonstrated in many studies. In particular, ageing is associated with a global loss of methylation state. Thus, the aim of future studies will be to analyze the weight of epigenetic changes in ageing and longevity.
| S-EPMC3402998 | biostudies-literature