SARS CoV2 infection _The longevity study perspectives.
ABSTRACT: Like other infectious diseases, COVID-19 shows a clinical outcome enormously variable, ranging from asymptomatic to lethal. In Italy, like in other countries, old male individuals, with one or more comorbidity, are the most susceptible group, and show, consequently, the highest mortality, and morbidity, including lethal respiratory distress syndrome, as the most common complication. In addition, another extraordinary peculiarity, that is a surprising resistance to COVID-19, characterizes some Italian nonagenarians/centenarians. Despite having the typical COVID-19 signs and/or symptoms, such exceptional individuals show a surprising tendency to recover from illness and complications. On the other hand, long-lived people have an optimal performance of immune system related to an overexpression of anti-inflammatory variants in immune/inflammatory genes, as demonstrated by our and other groups. Consequently, we suggest long-lived people as an optimal model for detecting genetic profiles associated with the susceptibility and/or protection to COVID-19, to utilize as potential pharmacological targets for preventing or reducing viral infection in more vulnerable individuals.
Project description:Italy was the first European nation to be affected by COVID-19. The biggest cluster of cases occurred in Lombardy, the most populous Italian region, and elderly men were the population hit in the hardest way. Besides its high infectivity, COVID-19 causes a severe cytokine storm and old people, especially those with comorbidities, appear to be the most vulnerable, presumably in connection to inflammaging. In centenarians inflammaging is much lower than predicted by their chronological age and females, presenting survival advantage in almost all centenarian populations, outnumber males, a phenomenon particularly evident in Northern Italy. Within this scenario, we wondered if: a) the COVID-19 mortality in centenarians was lower than that in people aged between 50 and 80 and b) the mortality from COVID-19 in nonagenarians and centenarians highlighted gender differences.We checked COVID-19-related vulnerability/mortality at the peak of infection (March 2020), using data on total deaths (i.e. not only confirmed COVID-19 cases). Our conclusion is that excess mortality increases steadily up to very old ages and at the same time men older than 90 years become relatively more resilient than age-matched females.
Project description:The human forkhead box O3A gene (FOXO3A) encodes an evolutionarily conserved key regulator of the insulin-IGF1 signaling pathway that is known to influence metabolism and lifespan in model organisms. A recent study described 3 SNPs in the FOXO3A gene that were statistically significantly associated with longevity in a discovery sample of long-lived men of Japanese ancestry [Willcox et al. (2008) Proc Natl Acad Sci USA 105:13987-13992]. However, this finding required replication in an independent population. Here, we have investigated 16 known FOXO3A SNPs in an extensive collection of 1,762 German centenarians/nonagenarians and younger controls and provide evidence that polymorphisms in this gene were indeed associated with the ability to attain exceptional old age. The FOXO3A association was considerably stronger in centenarians than in nonagenarians, highlighting the importance of centenarians for genetic longevity research. Our study extended the initial finding observed in Japanese men to women and indicates that both genders were likely to be equally affected by variation in FOXO3A. Replication in a French centenarian sample generated a trend that supported the previous results. Our findings confirmed the initial discovery in the Japanese sample and indicate FOXO3A as a susceptibility gene for prolonged survival in humans.
Project description:INTRODUCTION:Genetic factors contribute to the variation of human life span which is believed to be more profound after 85 years of age. The aim of the present study was to evaluate the frequency of 5 gene polymorphisms between nonagenarians, centenarians and average individuals. MATERIAL AND METHODS:Single nucleotide polymorphisms (SNPs) of telomerase reverse transcriptase (TERT; rs2736098), insulin-like growth factor-1 binding protein-3 (IGFBP3; A-202C, rs2857744), fork-head box O3A (FOXO3A; rs13217795 and rs2764264) factor and adiponectin (ADIPOQ; rs2241766) were evaluated in 405 individuals: n = 256 nonagenarians and centenarians (study group) and n = 149 average lifespan individuals (control group aged 18 - < 80 years). RESULTS:The frequency of women was significantly higher in the study group than the control group (64.5 vs. 49.7%, p = 0.004). Genotypic and allele frequencies did not differ between groups according to gender. However, in men, the frequency of TT genotype of FOXO3A; rs2764264 was higher in the study group than the control group (45.6 vs. 28.0%, p = 0.05). Overall, the frequency of the C allele of FOXO3A; rs2764264 was significantly lower in the study group than the control group (3.9 vs. 9.5%, respectively, p = 0.023). Furthermore, in the study group, the T allele was significantly more frequent in the nonagenarians (n = 239) than the centenarians (n = 17) in both FOXO3A; rs13217795 and rs2764264 (64.4 vs. 44.1%, p = 0.018 and 69.7 vs. 50.0%, p = 0.017, respectively). CONCLUSIONS:According to survival status, there is differentiation in the prevalence of both studied FOXO3A gene polymorphisms. The study group had half of the C alleles compared with the control group and centenarians less frequently had the T allele of both FOXO3A gene polymorphisms compared with nonagenarians. No difference was found between groups according to TERT, IGFBP3 and ADIPOQ gene polymorphisms. It seems that some polymorphisms may be significant in prolonging our lifespan. Nevertheless, confirmation in additional study populations is needed.
Project description:BACKGROUND:COVID-19 and the resultant lockdowns have caused a global discomposure. Out of a plethora of ramifications of this unusual state, mental health problems are becoming a serious concern. Considering the peculiarity of the situation, encapsulation of the lived experiences of people affected by COVID-19 may lead us towards a better understanding and control of the situation. AIM:The aim of the present study was to get an in-depth analysis of the lived experiences of Indian youth amid COVID-19 crisis and its impact on their mental health. METHOD:Ten college going students were telephonically interviewed using a semi-structured interview schedule to elicit participants' experiences with COVID-19 and the impact it has posed on their mental health. Transcripts were analysed using Interpretative Phenomenological Analysis (IPA). RESULTS:The analysis revealed three master themes: (1) 'Impact on mental health', (2) 'Positive experiences' and (3) 'Ways of coping amid the crisis'. CONCLUSION:The study draws attention to the mental health concerns of Indian youth amid the current crisis. The findings also highlight the positive outcomes of the crisis as well as the different ways of coping adopted by young individuals in India.
Project description:FOXO3, AKT1 and IGF-2R are critical members of the insulin/IGF-1 signaling pathway. Previous studies showed that polymorphisms (SNPs) in FOXO3, AKT1 and IGF-2R were associated with human longevity in Caucasian population. However, the association of these SNPs in different ethnic groups is often inconsistent. Here, we investigated the association of genetic variants in three genes with human longevity in Han Chinese population. Twelve SNPs from FOXO3, AKT1 and IGF-2R were selected and genotyped in 1202 long-lived individuals (nonagenarians and centenarians) and younger individuals. Rs9486902 of FOXO3 was found to be associated with human longevity in both genders combined in this study (allelic P = 0.002, corrected P = 0.024). The other eleven SNPs were not significantly associated with human longevity in Han Chinese population. The haplotypes TTCTT, CCTTC and CTCCT of FOXO3 as well as GGTCGG and GGTCAG of AKT1 were shown to have a significant difference between case and control (P =0.006, 2.78×10-5, 4.68×10-6, 0.003,0.005, respectively). The estimated prevalence of diabetes and prediabetes in long-lived individuals was significantly lower than in common adult populations (P = 0.001, 2.3×10-26) .Therefore, the search for longevity-associated genes provides the identification of new potential targets beneficial for the treatment of diabetes.
Project description:In addition to APOE and FOXO3, AKT1 has recently been suggested as a third consistent longevity gene, with variants in AKT1 found to be associated with human lifespan in two previous studies. Here, we evaluated AKT1 as a longevity-associated gene across populations by attempting to replicate the previously identified variant rs3803304 as well as by analyzing six additional AKT1 single-nucleotide polymorphisms, thus capturing more of the common variation in the gene. The study population was 2996 long-lived individuals (nonagenarians and centenarians) and 1840 younger controls of Danish and German ancestry. None of the seven SNPs tested were significantly associated with longevity in either a case-control or a longitudinal setting, although a supportive nominal indication of a disadvantageous effect of rs3803304 was found in a restricted group of Danish centenarian men. Overall, our results do not support AKT1 as a universal longevity-associated gene.
Project description:Aging is a universal and complex process that affects all tissues and cells types, including immune cells, in a process known as immunosenescence. However, many aspects of immunosenescence are not completely understood, as the characteristics of the immune cells of nonagenarians and centenarians or the features and implications of extracellular vesicles (EVs). In this study, we analyzed blood samples from 51 individuals aged 20-49 and 70-104 years. We found that senescent CD8 cells accumulate with age, while there is a partial reduction of senescent CD4 cells in nonagenarians and centenarians. Moreover, plasma EVs carry T cell specific markers, but no accumulation of "senescent-like EVs" was found within any of analyzed age groups. Our functional studies of cocultures of peripheral blood mononuclear cells and EVs showed that EVs enhance T cell viability and, under phytohemagglutinin stimulation, they influence cytokine secretion and cell activation in an age-dependent manner. These results underline the importance of EVs on the immune system functioning, and open new perspectives to further study their implication in human aging.
Project description:Copy number variants (CNVs) represent a significant source of genetic variation in the human genome and have been implicated in numerous diseases and complex traits. To date, only a few studies have investigated the role of CNVs in human lifespan. To investigate the impact of CNVs on prospective mortality at the extreme end of life, where the genetic component of lifespan appears most profound, we analyzed genomewide CNV data in 603 Danish nonagenarians and centenarians (mean age 96.9 years, range 90.0-102.5 years). Replication was performed in 500 long-lived individuals from the Leiden Longevity Study (mean age 93.2 years, range 88.9-103.4 years). First, we assessed the association between the CNV burden of each individual (the number of CNVs, the average CNV length, and the total CNV length) and mortality and found a significant increase in mortality per 10 kb increase in the average CNV length, both for all CNVs (hazard ratio (HR) = 1.024, P = 0.002) and for duplications (HR = 1.011, P = 0.005), as well as per 100 kb increase in the total length of deletions (HR = 1.009, P = 0.0005). Next, we assessed the relation between specific deletions and duplications and mortality. Although no genome-wide significant associations were discovered, we identified six deletions and one duplication that showed consistent association with mortality in both or either of the sexes across both study populations. These results indicate that the genome-wide CNV burden, specifically the average CNV length and the total CNV length, associates with higher mortality in long-lived individuals.
Project description:<h4>Background</h4>Centenarians are known to be successful agers compared to other older adults.<h4>Objective</h4>The 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.<h4>Results</h4>A 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; <i>p</i> = 0.032). Mortality was significantly higher in centenarians than in younger residents (50% vs. 21.3%, respectively; <i>p</i> = 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.<h4>Conclusion</h4>Worsening 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.