A rare human centenarian variant of SIRT6 enhances genome stability and interaction with Lamin A.

Sirtuin 6 (SIRT6) is a deacylase and mono-ADP ribosyl transferase (mADPr) enzyme involved in multiple cellular pathways implicated in aging and metabolism regulation. Targeted sequencing of SIRT6 locus in a population of 450 Ashkenazi Jewish (AJ) centenarians and 550 AJ individuals without a family history of exceptional longevity identified enrichment of a SIRT6 allele containing two linked substitutions (N308K/A313S) in centenarians compared with AJ control individuals. Characterization of this SIRT6 allele (centSIRT6) demonstrated it to be a stronger suppressor of LINE1 retrotransposons, confer enhanced stimulation of DNA double-strand break repair, and more robustly kill cancer cells compared with wild-type SIRT6. Surprisingly, centSIRT6 displayed weaker deacetylase activity, but stronger mADPr activity, over a range of NAD+ concentrations and substrates. Additionally, centSIRT6 displayed a stronger interaction with Lamin A/C (LMNA), which was correlated with enhanced ribosylation of LMNA. Our results suggest that enhanced SIRT6 function contributes to human longevity by improving genome maintenance via increased mADPr activity and enhanced interaction with LMNA.

Should patients with exceptional longevity be treated for osteoporosis after a hip fracture?

BACKGROUND: There are no studies focusing on treatment for osteoporosis in patients with exceptional longevity after suffering a hip fracture. OBJECTIVE: To assess the advisability of initiating treatment for osteoporosis after a hip fracture according to the incidence of new fragility fractures after discharge, risk factors for mortality and long-term survival. DESIGN: Retrospective review. SETTING: A tertiary university hospital serving a population of ~425 000 inhabitants in Barcelona. SUBJECTS: All patients >95 years old admitted with a fragility hip fracture between December 2009 and September 2015 who survived admission were analysed until the present time. METHODS: Pre-fracture ambulation ability and new fragility fractures after discharge were recorded. Risk factors for 1-year and all post-discharge mortality were calculated with multivariate Cox regression. Kaplan-Meier survival curve analyses were performed. RESULTS: One hundred and seventy-five patients were included. Median survival time was 1.32 years [95% confidence interval (CI) 1.065-1.834], with a maximum of 9.2 years. Male sex [hazard ratio (HR) 2.488, 95% CI 1.420-4.358] and worse previous ability to ambulate (HR 2.291, 95% CI 1.417-3.703) were predictors of mortality. After discharge and up to death or the present time, 10 (5.7%) patients had a new fragility fracture, half of them during the first 6 months. CONCLUSIONS: Few new fragility fractures occurred after discharge and half of these took place in the first 6 months. The decision to start treatment of osteoporosis should be individualised, bearing in mind that women and patients with better previous ambulation ability will have a better chance of survival.

Centenarians, semi and supercentenarians, COVID-19 and Spanish flu: a serological assessment to gain insight into the resilience of older centenarians to COVID-19.

BACKGROUND: Although it is well known that the older people have been the most susceptible to COVID-19, there are conflicting data on the susceptibility of centenarians. Two epidemiological study have shown that older centenarians (> 101 years old at the time of the 2020 pandemic peak) are more resilient than the remaining centenarians, suggesting that this resilience might be linked to the 1918 Spanish Flu pandemic. To gain insight into this matter, specifically whether the resilience of older centenarians to SARS-CoV-2 infection is linked to the Spanish Flu they had been affected by, we conducted a retrospective serological study. This study examined serum samples from 33 centenarians, encompassing semi- (aged > 104 < 110 years, N = 7) and supercentenarians (aged > 109 years, N = 4), born between 1905 and 1922, against both SARS-CoV-2 and 1918 H1N1 pseudotype virus. RESULTS: Anamnestic and laboratory data suggest that SARS-CoV-2 infection occurred in 8 centenarians. The infection appeared to have been asymptomatic or mild, and hospitalization was not required, despite 3 out of 8 being between 109 and 110 years old. The levels of anti-spike antibodies in centenarians infected and/or vaccinated were higher, although not significantly, than those produced by a random sample of seventy-year-old individuals used as controls. All centenarians had antibody levels against the 1918 H1N1 virus significantly higher (almost 50 times) than those observed in the quoted group of seventy-year-old subjects, confirming the key role in maintaining immunological memory from a priming that occurred over 100 years ago. Centenarians whose blood was collected prior to the pandemic outbreak demonstrated neutralising antibodies against the 1918 H1N1 virus, but all these subjects tested negative for SARS-CoV-2. CONCLUSION: This retrospective study shows that older centenarians are quite resilient to COVID-19, as they are capable of producing good levels of neutralising antibodies and experiencing mild or asymptomatic disease. This could be attributed to the 1918 Spanish flu pandemic through mechanisms other than the presence of cross-reactive antibodies between the 1918 H1N1 virus and SARS-CoV-2. Another possibility is that the association is purely temporal, solely correlated with the advanced age of resilient centenarians compared to those born after 1918, since older centenarians are known to have better control of immune-inflammatory responses.

Profiles of centenarians' functioning: linking functional and cognitive capacity with depressive symptoms.

BACKGROUND: Despite most centenarians facing age-related declines in functional and cognitive capacities, the severity of these declines varies among individuals, as does the maintenance of good mental health (e.g., depressive symptoms) despite these declines. This study aims to examine this heterogeneity in centenarians from the Second Heidelberg Centenarian Study, which collected data from 112 centenarians living in Germany. In our study, we focus on a subsample of 73 centenarians who provided self-reports for our measures of interest (M age = 100.4, SD age = 0.55). METHODS: We examined correlations between functional capacity (i.e., PADL, IADL), cognitive capacity (i.e., MMSE), and depressive symptoms (i.e., GDS), and the existence of different profiles using hierarchical clustering. RESULTS: Higher functional capacity was related to higher cognitive capacity and to fewer depressive symptoms. Yet, higher cognitive capacity was associated with more depressive symptoms. Hierarchical clustering analysis elucidated this contradiction by identifying three profiles: low-capacity individuals (i.e., 24 individuals had low functional and cognitive capacities, with low depressive symptoms), high-capacity individuals (i.e., 33 individuals with high functional and cognitive capacities, with low depressive symptoms), and low-functional-high-cognitive-capacity individuals (i.e., 16 individuals showed low functional but high cognitive capacity, with high depressive symptoms). Our post-hoc analyses highlighted arthritis and pain as risk factors for functional dependence and depression. CONCLUSIONS: Our findings emphasize the importance of identifying centenarian subgroups with specific resource- and risk profiles to better address their needs, and of treating pain to improve functional capacity and mental health in centenarians.

Cognitively healthy centenarians are genetically protected against Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) prevalence increases with age, yet a small fraction of the population reaches ages > 100 years without cognitive decline. We studied the genetic factors associated with such resilience against AD. METHODS: Genome-wide association studies identified 86 single nucleotide polymorphisms (SNPs) associated with AD risk. We estimated SNP frequency in 2281 AD cases, 3165 age-matched controls, and 346 cognitively healthy centenarians. We calculated a polygenic risk score (PRS) for each individual and investigated the functional properties of SNPs enriched/depleted in centenarians. RESULTS: Cognitively healthy centenarians were enriched with the protective alleles of the SNPs associated with AD risk. The protective effect concentrated on the alleles in/near ANKH, GRN, TMEM106B, SORT1, PLCG2, RIN3, and APOE genes. This translated to >5-fold lower PRS in centenarians compared to AD cases (P = 7.69 × 10-71), and 2-fold lower compared to age-matched controls (P = 5.83 × 10-17). DISCUSSION: Maintaining cognitive health until extreme ages requires complex genetic protection against AD, which concentrates on the genes associated with the endolysosomal and immune systems. HIGHLIGHTS: Cognitively healthy cent enarians are enriched with the protective alleles of genetic variants associated with Alzheimer's disease (AD). The protective effect is concentrated on variants involved in the immune and endolysosomal systems. Combining variants into a polygenic risk score (PRS) translated to > 5-fold lower PRS in centenarians compared to AD cases, and ≈ 2-fold lower compared to middle-aged healthy controls.

Agreement among different fatigue scales in people with extreme longevity and their offsprings: The FACET experience.

Fatigue is a symptom frequently complained about by older people but unfortunately poorly understood given its subjectivity and the lack of a gold standard for its assessment. The purpose of this study was therefore to preliminarily explore agreement among four different fatigue scales in a sample of persons with extreme longevity (PEL), their direct offsprings (DO), and controls (CO) matched for age and sex with DO. κ statistics was used to quantify agreement among four different fatigue scales. The agreement ranged from mild to substantial and almost perfect agreement depending on the group considered. The highest agreement was found between the Multidimensional Assessment of Fatigue scale and the Short Form Health Survey-36-Vitality Subscale in the PEL group (κ 0.820; 95 % CI 0.471-0.947). These preliminary findings may serve as a guide in selecting the most feasible instrument to assess fatigue in future large-scale research and clinical activities involving older people.

Mental health among centenarians living in Switzerland.

BACKGROUND: Given the increasing number of people achieving exceptionally long lifespans, there is an urgent need for a better understanding of mental health in centenarians. This study aimed to understand the prevalence of mental health conditions-depressive symptoms, anxiety, sleep disturbances, disinhibition, and aberrant motor behaviour-among centenarians in Switzerland. METHODS: Data were collected from N = 169 participants via telephone interviews or paper questionnaires, either directly from centenarians or through proxy informants. Half the data were collected during a period when protective measures were imposed due to the COVID-19 pandemic, and half were collected after the measures were lifted. RESULTS: Mental health conditions were prevalent in our sample, particularly depressive symptoms (44.51%) and anxiety (42.17%). Significant positive associations were found between depressive symptoms and anxiety, and between disinhibition and aberrant motor behaviour. Furthermore, we identified statistical predictors for the occurrence of mental health conditions. Notably, institutionalised living increased the odds of depressive symptomatology, while those with higher education levels or an absence of cognitive impairment experienced more sleep disturbances. Finally, cognitive impairment was linked to increased disinhibition and aberrant motor behaviour. CONCLUSIONS: The high prevalence of mental health conditions underscores the need for proactive mental health care strategies in advanced old age. Moreover, it is vital to consider the interconnected nature of mental health conditions and to prioritise vulnerable groups, such as centenarians in institutional settings.

Challenges in anti-aging medicine-trends in biomarker discovery and therapeutic interventions for a healthy lifespan.

We are facing a growing aging population, along with increasing pressure on health systems, caused by the impact of chronic co-morbidities (i.e. cancer, cardiovascular and neurodegenerative diseases) and functional disabilities as people age. Relatively simple preventive lifestyle interventions, such as dietary restriction and physical exercise, are important contributors to active and healthy aging in the general population. However, as shown in model organisms or in 'in vitro' conditions, lifestyle-independent interventions may have additional health benefits and can even be conceived as possible reversers of the aging process. Thus, pharmaceutical laboratories, research institutes, and universities are putting more and more effort into finding new molecular pathways and druggable targets to develop gerotherapeutics. One approach is to target the driving mechanisms of aging, some of which, like cellular senescence and impaired autophagy, we discussed in an update on the biology of aging at AgingFit 2023 in Lille, France. We underline the importance of carefully and extensively testing senotherapeutics, given the pleiotropism and heterogeneity of targeted senescent cells within different organs, at different time frames. Other druggable targets emerging from new putative mechanisms, like those based on transcriptome imbalance, nucleophagy, protein phosphatase depletion, glutamine metabolism, or seno-antigenicity, have been evidenced by recent preclinical studies in classical models of aging but need to be validated in humans. Finally, we highlight several approaches in the discovery of biomarkers of healthy aging, as well as for the prediction of neurodegenerative diseases and the evaluation of rejuvenation strategies.

Decoding the role of long noncoding RNAs in the healthy aging of centenarians.

Aging is the largest risk factor of major human diseases. Long noncoding RNAs (lncRNAs) as the key regulatory elements have shown a strong impact on multiple biological processes as well as human disease mechanisms. However, the roles of lncRNAs in aging/healthy aging processes remain largely unknown. Centenarians are good models for healthy aging studies due to avoiding major chronic diseases and disabilities. To illustrate their ubiquitous nature in the genome and the 'secrets' of healthy aging regulation from the perspective of lncRNAs, peripheral blood samples from two regions consisting 76 centenarians (CENs), 54 centenarian-children (F1) and 41 spouses of centenarian-children (F1SP) were collected for deep RNA-seq. We identified 11 CEN-specific lncRNAs that is particularly expressed in longevous individuals. By kmers clustering, hundreds of human lncRNAs show similarities with CEN-specific lncRNAs, especially with ENST00000521663 and ENST00000444998. Using F1SP as normal elder controls (age: 59.9 ± 6.6 years), eight lncRNAs that are differentially expressed in longevous elders (CEN group, age: 102.2 ± 2.4 years) were identified as candidate aging/health aging-related lncRNAs (car-lncs). We found that the expression of eight car-lncs in human diploid fibroblasts displayed dynamic changes during cell passage and/or H2O2/rapamycin treatment; of which, overexpression either of THBS1-IT1 and THBS1-AS1, two lncRNAs that highly expressed in CENs, can remarkably decrease p16, p21 and the activity of senescent related ß-galactosidase, suggesting that THBS1-IT1 and THBS1-AS1 can inhibit cellular senescence. We provided the first comprehensive analysis of lncRNA expression in longevous populations, and our results hinted that dysregulated lncRNAs in CENs are potential protective factors in healthy aging process.

The rosetta stone of successful ageing: does oral health have a role?

Ageing is an inevitable aspect of life and thus successful ageing is an important focus of recent scientific efforts. The biological process of ageing is mediated through the interaction of genes with environmental factors, increasing the body's susceptibility to insults. Elucidating this process will increase our ability to prevent and treat age-related disease and consequently extend life expectancy. Notably, centenarians offer a unique perspective on the phenomenon of ageing. Current research highlights several age-associated alterations on the genetic, epigenetic and proteomic level. Consequently, nutrient sensing and mitochondrial function are altered, resulting in inflammation and exhaustion of regenerative ability.Oral health, an important contributor to overall health, remains underexplored in the context of extreme longevity. Good masticatory function ensures sufficient nutrient uptake, reducing morbidity and mortality in old age. The relationship between periodontal disease and systemic inflammatory pathologies is well established. Diabetes, rheumatoid arthritis and cardiovascular disease are among the most significant disease burdens influenced by inflammatory oral health conditions. Evidence suggests that the interaction is bi-directional, impacting progression, severity and mortality. Current models of ageing and longevity neglect an important factor in overall health and well-being, a gap that this review intends to illustrate and inspire avenues for future research.

Is the relationship between erythropoiesis and renal function one of the secrets of extreme longevity?

BACKGROUND AND AIMS: Renal function and erythropoiesis could be impaired with advancing age. Neutrophil gelatinase-associated lipocalin (NGAL) as well as erythropoietin (EPO) levels are two useful biomarkers of the renal status. In advanced age, the relationships between NGAL, EPO and hemoglobin (Hb) levels remains unknown. The aim of the present study is to evaluate the relationship between renal function and erythropoiesis in a small cohort of centenarians. METHODS AND RESULTS: We observed thirty-one healthy centenarians with normal hemoglobin levels, a mild reduction in eGFR and no need of erythropoiesis support. We found a significant inverse association between NGAL and GFR, hemoglobin levels and EPO, confirming the key role of the renal function on erythropoiesis also in extreme longevity. A gender difference emerged, showing female participants with lower eGFR and Hb values more than males. CONCLUSIONS: Our findings suggested a new link between renal function, erythropoiesis and longevity in centenarians and these could have relevant implications in clinical practice. These findings could explain why very old subjects presenting a slight GFR reduction seemed not to be exposed to a significant risk of mortality.

Association among Terminally Differentiated T Cells, Frailty, and Dependency in a Group of Cuban Centenarians.

INTRODUCTION: Centenarians are considered a model of successful aging. Cuba exhibits one of the oldest populations in Latin America with more than two thousand centenarians. METHODS: This study aimed to evaluate the immune phenotype of forty-three Cuban centenarians, their clinical characteristics such as comorbidities, frailty, body mass index, and some hemochemical parameters. RESULTS: Centenarians had normal body mass indexes, relatively good health status, and 21.95% of them had no comorbidities; 53.6% were classified as frail, and 7% were classified as robust. In addition, 17% of centenarians were independent, and 41.46% were moderately dependent. The seroprevalence against cytomegalovirus was 100%. Concerning pro-inflammatory markers, the majority of them had very low cytokine levels and serum C-reactive protein around the normal limit. We also found the predominance of memory subsets over naive compartments in CD4+ and CD8+ T cells. Terminally differentiated CD8+CD28- T cells were higher in frail centenarians than in pre-frail, while CD8+CD57+ and CD8+EMRA T cells were higher in moderately and severely dependent individuals than in independent individuals. Severely dependent centenarians had a lower CD4+/CD8+ ratio. CONCLUSION: This study describes for the first time the predominance of memory subsets over naive compartments in CD4+ and CD8+ T cells, as well as its relation to frailty and/or dependency in a group of Cuban centenarians. Further studies are needed to continue understanding the natural biological aging mechanism and the relationship between terminally differentiated lymphocytes and inflammaging in the context of extreme longevity.

Comparison of functional disabilities, place of death and end-of-life medical expenditures among centenarians and non-centenarians in China: a series of cross-sectional studies.

BACKGROUND: Long-term and end-of-life (EOL) care for older adults has become a global concern due to extended longevity, which is generally accompanied by increased rates of disability. However, differences in the rates of disability in activities of daily living (ADLs), place of death and medical expenditures during the last year of life between centenarians and non-centenarians in China remain unknown. This study aims to fill this research gap to inform policy efforts for the capacity-building of long-term and EOL care for the oldest-old, especially for centenarians in China. METHODS: Data from 20,228 decedents were derived from the 1998-2018 Chinese Longitudinal Healthy Longevity Survey. Weighted logistic and Tobit regression models were used to estimate differences in the prevalence of functional disability, rate of death in hospitals and EOL medical expenditures by age groups among oldest-old individuals. RESULTS: Of the 20,228 samples, 12,537 oldest-old individuals were female (weighted, 58.6%, hereafter); 3,767 were octogenarians, 8,260 were nonagenarians, and 8,201 were centenarians. After controlling for other covariates, nonagenarians and centenarians experienced a greater prevalence of full dependence (average marginal differences [95% CI]: 2.7% [0%, 5.3%]; 3.8% [0.3%, 7.9%]) and partial dependence (6.9% [3.4%, 10.3%]; 15.1% [10.5%, 19.8%]) but a smaller prevalence of partial independence (-8.9% [-11.6%, -6.2%]; -16.0% [-19.1%, -12.8%]) in ADLs than octogenarians. Nonagenarians and centenarians were less likely to die in hospitals (-3.0% [-4.7%, -1.2%]; -4.3% [-6.3%, -2.2%]). Additionally, nonagenarians and centenarians reported more medical expenditures during the last year of life than octogenarians with no statistically significant differences. CONCLUSION: The oldest-old experienced an increased prevalence of full and partial dependence in ADLs with increasing age and reported a decline in the prevalence of full independence. Compared with octogenarians, nonagenarians and centenarians were less likely to die in hospitals. Therefore, future policy efforts are warranted to optimise the service provision of long-term and EOL care by age patterns for the oldest-old population in China.

Trends in ages at death of Norwegian centenarians: the 1870-1904 birth cohorts.

BACKGROUND: With rapidly rising life expectancy and ageing populations, interest has grown in the survival patterns and ages at death at the highest ages. In Scandinavia, the accumulation of very old population segments coupled with long-established, high-quality population registers permit meaningful analysis. METHODS: This study is based on individual level data from extinct Norwegian birth cohorts using data obtained from the Norwegian Civil Register System. We assess trends in the ages at death of centenarians in Norway for cohorts born between 1870 and 1904 for evidence of any secular increase using quantile regression. RESULTS: We observed that there is no upward trend in centenarian lifespans, in line with recent observations in Sweden, but contrary to the upward trend at the very highest percentiles as observed in Denmark. CONCLUSIONS: The available evidence suggests that the stagnation in centenarian lifespans may be partly due to the failure to find ways of dealing with neurodegenerative diseases.

Severe cerebrovascular pathology of the first supercentenarian to be autopsied in the world.

We report on a 116-year-old Japanese woman who was the first officially documented supercentenarian to be autopsied in the world. She lived a remarkably healthy life until suffering cerebral infarction at 109 years of age. She became Japan's oldest person at 113 years and died in 1995 from colon cancer at 116 years 175 days. Her medical records show the delayed onset of stroke, cancer, dementia, and heart disease and the importance of appropriate medical treatment and intensive dedicated care provided during the last stage of her life. She was the longest-lived person in Japan for 21 years from 1993 until 2014. The neuropathological findings of her autopsied brain were briefly reported in the Japanese literature in 1997. In this study, we reinvestigated her brain and spinal cord in more detail. Severe cerebrovascular lesions and cervical spondylotic myelopathy were found to be the main causes of her disability. Although the density of senile plaques was relatively high, the distribution of neurofibrillary tangles was limited. Ghost tangles and argyrophilic grains were mild. The mildness of tau pathological changes in her neurons, in other words the resistance of neurons to tau pathology, may be a factor responsible for her longevity.

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.

Immunosenescence and inflammatory markers in Cuban centenarians: implications for survival.

Centenarians are the best example of successful aging in humans. This work aimed to understand if immune status is associated with survival in Cuban centenarians. In a previous study, our group enrolled 43 centenarians and evaluated their immune status and functional capacity. 41 out of 43 recruited centenarians received follow-up phone calls, during a period of 2 years. Absolute CD4 + T cell count was higher among survivors, while the frequency of CD8 + CCR7-CD45RA + , CD8 + CD45RA + CD28-, and CD4 + CD28- T cells was higher among non-survivors. We also found that higher frequencies of terminally differentiated T cells were related to a higher risk of death, while centenarians with higher frequencies of T cells were more likely to survive. Surprisingly, neither serum inflammatory markers nor frailty/dependency was associated with survival. Our preliminary study suggests that immuno-senescence markers, but not inflammaging or functional capacity, are associated with survival beyond 100 years in a small group of Cuban centenarians.

Study of neuropathological changes and dementia in 100 centenarians in The 90+ Study.

INTRODUCTION: The association between neuropathological changes and dementia among centenarians and nonagenarians remains unclear. METHODS: We examined brain tissue from 100 centenarians and 297 nonagenarians from The 90+ Study, a community-based longitudinal study of aging. We determined the prevalence of 10 neuropathological changes and compared their associations with dementia and cognitive performance between centenarians and nonagenarians. RESULTS: A total of 59% of centenarians and 47% of nonagenarians had at least four neuropathological changes. In centenarians, neuropathological changes were associated with higher odds of dementia and, compared to nonagenarians, the odds were not attenuated. For each additional neuropathological change, the Mini-Mental State Examination score was lower by 2 points for both groups. DISCUSSION: Neuropathological changes continue to be strongly related to dementia in centenarians, highlighting the importance of slowing or preventing the development of multiple neuropathological changes in the aging brain to maintain cognitive health. HIGHLIGHTS: Individual and multiple neuropathological changes are frequent in centenarians. These neuropathological changes are strongly associated with dementia. There is no attenuation of this association with age.

Cognition, function, and prevalent dementia in centenarians and near-centenarians: An individual participant data (IPD) meta-analysis of 18 studies.

INTRODUCTION: There are limited data on prevalence of dementia in centenarians and near-centenarians (C/NC), its determinants, and whether the risk of dementia continues to rise beyond 100. METHODS: Participant-level data were obtained from 18 community-based studies (N = 4427) in 11 countries that included individuals ≥95 years. A harmonization protocol was applied to cognitive and functional impairments, and a meta-analysis was performed. RESULTS: The mean age was 98.3 years (SD = 2.67); 79% were women. After adjusting for age, sex, and education, dementia prevalence was 53.2% in women and 45.5% in men, with risk continuing to increase with age. Education (OR 0.95;0.92-0.98) was protective, as was hypertension (odds ratio [OR] 0.51;0.35-0.74) in five studies. Dementia was not associated with diabetes, vision and hearing impairments, smoking, and body mass index (BMI). DISCUSSION: Among the exceptional old, dementia prevalence remains higher in the older participants. Education was protective against dementia, but other factors for dementia-free survival in C/NC remain to be understood.

A Comprehensive Analysis of Cytokine Network in Centenarians.

Cytokines have been investigated extensively in elderly people, with conflicting results. We performed a comprehensive analysis of the plasma levels of 62 cytokines and growth factors involved in the regulation of the immune system, in healthy centenarians, and middle-aged controls. We confirmed the previously observed increase in the levels of several pro-inflammatory cytokines, such as TNF-α and IL-6, and found that several other cytokines, directly or indirectly involved in inflammation (such as IFN-α, IL-23, CCL-5), were present at higher levels in centenarians. We did not observe any increase in the levels of anti-inflammatory cytokines, with the notable exception of the Th2-shifting cytokine IL-19. No relevant difference was observed in cytokines regulating T cell immunity. Several growth factors having a role in regulating immunity, such as G-CSF, GM-CSF, EGF, and VEGF, were upregulated in centenarians, too. Principal component analysis of the cytokine dataset showed that pro and anti-inflammatory cytokines were the variables that contributed the most to the variability of the data we observed.