Centenarians born before 1919 are resistant to COVID-19.

Although mortality from COVID-19 progressively increases with age, there are controversial data in the literature on the probability of centenarians dying from COVID-19. Moreover, it has been claimed that men in their 90s and 100s are more resilient than women. To gain insight into this matter, we analysed, according to gender, mortality data during the first year of pandemic of Sicilian nonagenarians and centenarians. We used mortality data from the 2019 as a control. The crude excess mortality between the two years was calculated. Data on deaths of Sicilian 90 + years show that, in line with what is known about the different response to infections between the two genders, oldest females are more resilient to COVID-19 than males. Moreover, centenarians born before 1919, but not "younger centenarians", are resilient to COVID-19. This latter datum should be related to the 1918 Spanish flu epidemic, although the mechanisms involved are not clear.

Depressive Symptoms of Centenarians during the COVID-19 Pandemic: Preliminary Results of an Exploratory Study in Switzerland

Introduction: Depression is one of the most frequent mental health problems in older populations.1 To the best of our knowledge, the prevalence of depressive symptomatology (DS) among centenarians in Switzerland is unknown. Furthermore, the COVID-19 pandemic may have had a negative impact. As part of the study SWISS1002, we intend to provide key information on centenarians' levels of DS. Objective(s): To describe the DS of Switzerland's centenarians during the COVID-19 pandemic. Method(s): Randomly selected centenarians from across Switzerland and their proxy relatives were invited to participate. Data are collected via telephone. The questionnaire includes the assessment of DS via the Geriatric Depression Scale (GDS)- 5 items.3 Preliminary data were analysed using descriptive statistics. Result(s): Telephone interviews were completed with 51 centenarians, and for 19 of them, proxy relatives also answered. The MAge of the centenarians was 101.41 (1.47) years, 34 (66.67%) were female and 27 (52.94%) lived at home. The mean score of the GDS-5 was 1.32 (SD=1.49). Considering a cut-off >=2, 18 (36%) centenarians were screened positive for possible depression. Descriptive statistics indicated effects of gender (men: M=1.41, SD=1.46;women: M=1.27, SD=1.53) and living situation (private: M=1.07, SD=1.36;institution: M=1.61, SD=1.62). Centenarians' and proxy reports were significantly related (rho=0.56;p<.05). Conclusion(s): Clinically relevant DS are highly prevalent among centenarians during the COVID-19 pandemic (36%), which is consistent with a recent study4 reporting a prevalence of 32% in a sample of younger older adults (MAge: 77.6, SD=6.9). To conclude, DS in centenarians should be screened systematically, especially in this time of unprecedented health crisis.

Extreme Longevity: Analysis of the Direct or Indirect Influence of Environmental Factors on Old, Nonagenarians, and Centenarians in Cilento, Italy.

Longevity is rightly considered one of the greatest achievements of modern society, an achievement understood as the possibility of increasing the healthy part of life and not only its full duration. This study investigated the phenomenon of regional longevity in Cilento by analyzing the association between longevity indicators and some environmental factors, in order to understand if factors such as altitude, climate, UNESCO protected areas, and hinterland can directly or indirectly influence the measure of healthy living and lead to longevity. Demographic and environmental data were collected through the Archives of the Cilento municipalities, the National Institute of Statistics, the Italian Institute for Environmental Protection and Research, and the Italian National Commission for UNESCO. The Geographically Weighted Regression were used to determine the association between longevity indicators and environmental factors. Correlation analysis between the longevity indicators was investigated in order to have a complete picture of longevity in Cilento. It was discovered that Cilento longevity is mainly found in the central area of the territory and from there, by age groups, it widens towards the south-eastern area. This designated area is part of the hilly area of the Cilento, at an altitude between 400 and 700 m above sea level. The towns of this area are part of the UNESCO heritage and are characterized by a transitional climate between Mediterranean and temperate climate. Moreover, the correlation analysis between the six indicators of longevity has confirmed a linear relationship between the six variables and this indicates that in the years to come there will be the probabilities of a generational turn over between the old, great old, nonagenarians and current centenarians, provided that the SARS-CoV-2 pandemic subsides.

Centenarians exposed to the Spanish flu in their early life better survived to COVID-19.

BACKGROUND: Although 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. METHODS: We 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. FINDINGS: The 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. INTERPRETATION: In 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.

Immunosenescence and inflammaging in the aging process: age-related diseases or longevity?

During aging the immune system (IS) undergoes remarkable changes that collectively are known as immunosenescence. It is a multifactorial and dynamic phenomenon that affects both natural and acquired immunity and plays a critical role in most chronic diseases in older people. For a long time, immunosenescence has been considered detrimental because it may lead to a low-grade, sterile chronic inflammation we proposed to call "inflammaging" and a progressive reduction in the ability to trigger effective antibody and cellular responses against infections and vaccinations. Recently, many scientists revised this negative meaning because it can be considered an essential adaptation/remodeling resulting from the lifelong immunological biography of single individuals from an evolutionary perspective. Inflammaging can be considered an adaptive process because it can trigger an anti-inflammatory response to counteract the age-related pro-inflammatory environment. Centenarians represent a valuable model to study the beneficial changes occurring in the IS with age. These extraordinary individuals reached the extreme limits of human life by slowing down the aging process and, in most cases, delaying, avoiding or surviving the major age-associated diseases. They indeed show a complex and heterogeneous phenotype determined by an improved ability to adapt and remodel in response to harmful stimuli. This review aims to point out the intimate relationship between immunosenescence and inflammaging and how these processes impact unsuccessful aging rather than longevity. We also describe the gut microbiota age-related changes as one of the significant triggers of inflammaging and the sex/gender differences in the immune system of the elderly, contributing to the sex/gender disparity in terms of epidemiology, pathophysiology, symptoms and severity of age-related diseases. Finally, we discuss how these phenomena could influence the susceptibility to COVID-19 infection.

Hypothetical COVID-19 protection mechanism: hints from centenarians.

The risk of serious complications and the fatality rate due to COVID-19 pandemic have proven particularly higher in older persons, putting a further strain in healthcare system as we dramatically observed.COVID-19 is not exclusively gerophile (géro "old" and philia "love") as young people can be infected, even if older people experience more severe symptoms and mortality due to their greater frailty. Indeed, frailty could complicate the course of COVID-19, much more than the number of years lived. As demonstration, there are centenarians showing remarkable capacity to recover after coronavirus infection.We hypothesize that centenarian's portfolio could help in identifying protective biological mechanisms underlying the coronavirus infection.The human leukocyte antigen (HLA) is one of the major genetic regions associated with human longevity, due to its central role in the development of adaptive immune response and modulation of the individual's response to life threatening diseases. The HLA locus seems to be crucial in influencing susceptibility and severity of COVID-19.In this hypothesis, we assume that the biological process in which HLA are involved may explain some aspects of coronavirus infection in centenarians, although we cannot rule out other biological mechanisms that these extraordinary persons are able to adopt to cope with the infection.

Centenarians in nursing homes during the COVID-19 pandemic.

BACKGROUND: Centenarians are known to be successful agers compared to other older adults. OBJECTIVE: 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. RESULTS: 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; 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. CONCLUSION: 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.

SARS CoV2 infection _The longevity study perspectives.

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.

COVID-19 mortality in Lombardy: the vulnerability of the oldest old and the resilience of male centenarians.

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.