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.
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.
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.
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.
Project description:Molecular changes underlying the persistent health effects after SARS-CoV-2 infection remain poorly understood. To discern the gene regulatory landscape in the upper respiratory tract of COVID-19 patients, we performed enzymatic DNA methylome and single-cell RNA sequencing in nasal cells of COVID-19 patients (n=19, scRNA-seq n=14) and controls (n=14, scRNA-seq n=10). In addition, we re-sampled a subset of these patients for transcriptome analyses at 3 (n=7) and 12 months (n=5) post-infection and followed the expression of differentially regulated genes over time. Genome-wide DNA methylation analysis revealed 3,112 differentially methylated regions between COVID-19 patients and controls. Hypomethylated regions affected immune regulatory genes, while hypermethylated regions were associated with genes governing ciliary function. These genes were not only downregulated in the acute phase of disease but sustained repressed up to 12 months post-infection in ciliated cells. Validation in an independent cohort collected 6 months post-infection (n=15) indicated a symptom-dependent transcriptional repression of ciliary genes. We therefore propose that hypermethylation observed in the acute phase may exert a long-term effect on gene expression, possibly contributing to post-acute COVID-19 sequelae.
Project description:IntroductionPopulation longevity is a global phenomenon influenced by various factors including social, economic transitions, and medical advancements. The study focused on the population over 95 years old, adopting an approach that integrates data from the 2018 Census and geospatial analysis techniques.MethodsAn ecological study was conducted using anonymized microdata from the 2018 National Population and Housing Census (CNPV). Geographic analysis, choropleth maps, and Kernel density estimation were employed to identify clusters of individuals aged over 95 years.ResultsThe study identified 43,427 individuals aged 95 years or older in Colombia, with concentrations observed in departments such as Antioquia and Bogotá. Analysis by department and municipality revealed variations in rates and sex distribution. Kernel density analysis highlighted clusters in the Valle de Tenza area and other regions.ConclusionThis study sheds light on the geographical distribution of centenarians in Colombia, emphasizing clusters in certain regions. More research is needed to understand the individual and contextual factors underlying successful aging in Colombia and to inform policies to improve the quality of life of older populations.
Project description:The COVID-19 pandemic, caused by SARS-CoV-2, prompted global efforts to develop vaccines to control the disease. Various vaccines, including mRNA (BNT162b2, mRNA-1273), adenoviral vector (ChAdOx1, Ad26.COV2.S), and inactivated virus platforms (BBIBP-CorV, CoronaVac), elicit high-titer, protective antibodies against the virus, but long-term antibody durability and effectiveness vary. The objective of this study is to elucidate the factors that influence vaccine effectiveness (VE) and the longevity of humoral immune responses to COVID-19 vaccines through a review of the relevant literature, including clinical and real-world studies. Here, we discuss the humoral immune response to different COVID-19 vaccines and identify factors influencing VE and antibody longevity. Despite initial robust immune responses, vaccine-induced immunity wanes over time, particularly with the emergence of variants, such as Delta and Omicron, that exhibit immune escape mechanisms. Additionally, the durability of the humoral immune responses elicited by different vaccine platforms, along with the identification of essential determinants of long-term protection-like pre-existing immunity, booster doses, hybrid immunity, and demographic factors-are critical for protecting against severe COVID-19. Booster vaccinations substantially restore neutralizing antibody levels, especially against immune-evasive variants, while individuals with hybrid immunity have a more durable and potent immune response. Importantly, comorbidities such as diabetes, cardiovascular disease, chronic kidney disease, and cancer significantly reduce the magnitude and longevity of vaccine-induced protection. Immunocompromised individuals, particularly those undergoing chemotherapy and those with hematologic malignancies, have diminished humoral responses and benefit disproportionately from booster vaccinations. Age and sex also influence immune responses, with older adults experiencing accelerated antibody decline and females generally exhibiting stronger humoral responses compared to males. Understanding the variables affecting immune protection is crucial to improving vaccine strategies and predicting VE and protection against COVID-19.
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.
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.