Search Results (111)

This study aims to characterise the B cell compartment in a cohort of Sicilian centenarians by analysing absolute CD3⁻CD19⁺ lymphocyte counts, in association with age, sex, cytomegalovirus (CMV) serostatus, related to immune ageing, and interleukin (IL)-6 levels, representative of inflamm-ageing. It also investigates age-related changes in the CD4⁺/CD19⁺ ratio as a marker of immune ageing, reflecting shifts in immune homeostasis. B cell counts were assessed by flow cytometry on 53 Sicilians aged 19–110 years: 20 Adults, 15 Older adults, 11 long-living individuals, and 7 oldest centenarians. A multiple negative binomial regression was applied to evaluate the effects of age, sex, CMV serostatus, and Il-6 levels on values of B cells. The results showed a non-significant trend toward age-related decline without sex-based differences. A significant reduction in B cell count was observed in individuals with high anti_CMV titres, while IL-6 levels showed a borderline inverse correlation. CD4⁺/CD19⁺ ratio values showed an age-related increase. Our findings suggest that the age-related decline in B cell numbers may be mostly related to CMV infection and IL-6 values, without sex contribution. The age-related increase in the CD4⁺/CD19⁺ ratio, most pronounced in oldest centenarians, may represent a compensatory adaptation promoting immune regulation and chronic inflammation control. Full article

Chronic low-grade inflammation, or “inflammaging,” represents a central mechanism linking dietary patterns, gut microbiome composition, and biological aging. Evidence from Blue Zone populations and Mediterranean diet studies demonstrates that specific nutritional interventions are associated with up to 23% lower all-cause mortality, with analyses suggesting that part of this association may be mediated by measurable improvements in inflammatory biomarkers. This paper synthesizes published evidence from Mediterranean diet trials, centenarian microbiome studies, and digital health platforms to propose a comprehensive digital health framework that integrates quarterly inflammation and microbiome monitoring with continuous lifestyle tracking to deliver personalized longevity interventions. This paper introduces the Longevity-Inflammation Index (L-II), a composite score combining high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-alpha, and microbiome-derived markers, with scoring algorithms derived from centenarian population studies. The proposed platform leverages artificial intelligence to generate evidence-based recommendations adapted from centenarian and Mediterranean dietary patterns. Published evidence from multiple randomized controlled trials demonstrates that Mediterranean dietary interventions reduce hs-CRP by 18–32%, increase microbiome diversity by 6–28%, and improve metabolic markers including HOMA-IR and TG/HDL ratios. Digital health platforms demonstrate sustained engagement rates of 58–84% at 12 months, with dietary logging frequencies of 4–6 days per week. Cost-effectiveness analyses of dietary interventions show incremental cost-effectiveness ratios of USD 2100–4800 per quality-adjusted life year gained. This inflammation-centered digital health framework offers a scalable approach for translating longevity research into practical interventions for healthy aging, with validation studies needed to confirm the integrated platform’s efficacy and real-world implementation feasibility. Full article

Ensuring healthy lives is both crucial for residents’ quality of life and a core objective of the Sustainable Development Goals. While numerous studies have examined the drivers of human health, few have distinguished between average health and extreme health outcomes. Moreover, the nonlinear effects of various determinants on multidimensional human health remain underexplored. This study aims to investigate the spatially varying contributions of natural and socioeconomic factors to multidimensional human health, focusing particularly on their nonlinear relationships. We first quantified multidimensional human health at the prefectural level of China, including average health (Life Expectancy), extreme health (Longevity Index and Centenarian Index), and subjective health (Self-Rated Health). We then combined the Geographically Weighted Random Forest model with the SHAP interpretations to investigate the impacts of natural and socioeconomic factors. Through the GWRF-SHAP framework, we estimated the nonlinear relationships between the four health indicators and their key influencing factors. We found that: (1) The four health indicators exhibited significant positive correlations, except for the relationship between Centenarian Index and Self-Rated Health. (2) Extreme health outcomes (Longevity and Centenarian Index) were predominantly influenced by natural factors, whereas average and subjective health (Life Expectancy and Self-Rated Health) were more strongly associated with socioeconomic conditions. (3) The dominant determinants of human health varied across regions, but socioeconomic factors generally showed stronger influences in northwestern China. (4) Both socioeconomic and natural factors exhibited nonlinear effects and threshold behaviors on health outcomes. These findings suggest that improving socioeconomic conditions is beneficial for enhancing both average and subjective health, whereas managing the natural environment is crucial for promoting extreme levels of health. Our study advocates a multidimensional, spatially tailored, and threshold-sensitive approach to health management. Full article

Despite the health concerns regarding alcohol and its link to cancer, moderate consumption of red wine has been associated with healthy aging and longevity, defined as up to one drink per day for women and two drinks per day for men (approximately 142 mL or 5 oz per drink). Previous research has revealed the health benefits of red wine, particularly in relation to cardiovascular disease. However, the influence of genetic factors on these benefits remains to be elucidated. In this study, we explored genes linked to red wine and created a curated gene set that intersects with those related to centenarians, which are markers of exceptional longevity. By analyzing literature from over 190 databases, we identified and validated a curated list of 43 genes associated with red wine and centenarians. We conducted gene set enrichment analysis as well as enrichment analysis of diseases and their tissue distributions. The results suggest that these genes play a crucial role in stress response and apoptosis, which are essential for cell survival and renewal. Additionally, these genes were enriched in pathways associated with smooth muscle cell proliferation, neuroinflammation, nucleotide excision repair, and lipoprotein metabolism (false discovery rate, FDR < 3 × 10⁻⁷). Gene set enrichment analysis indicated significant tissue distribution in the gastrointestinal, cardiovascular, and respiratory systems. Furthermore, the disease–gene enrichment analysis pointed to associations with diseases related to tissues and organs, including cardiovascular disease (heart disease and stroke), type 2 diabetes, gastrointestinal diseases and metabolic diseases, immune diseases, and cancer (FDR < 9.37 × 10⁻⁶); notably, cardiovascular diseases, diabetes, and cancer are leading causes of death, suggesting that these genes may be protective against those diseases. Our review of the literature indicates that individuals who do not currently drink alcohol should not be encouraged to start. However, we propose that moderate consumption of red wine, especially for middle-aged to older adults after 40 years old, can provide significant health benefits due to its components and the positive effects of hormesis. Although further research is necessary to uncover additional genes, this study provides the first genetic overview of the health benefits of red wine, emphasizing its potential in supporting healthy aging and longevity. Full article

Sirtuins (SIRT1–SIRT7) are NAD⁺-dependent deacetylases that link cellular energy status to chromatin maintenance, mitochondrial function and inflammatory signaling. While modulation of SIRT1, SIRT3 and SIRT6 extends lifespan in model organisms, evidence in extreme-age humans is scarce. We quantified protein and mRNA levels, and protein-to-mRNA ratios for SIRT1, SIRT3 and SIRT6 in buccal epithelial cells obtained from healthy young adults, middle/late-aged individuals and nonagenarians/centenarians residing in a longevity-enriched region of south-eastern Azerbaijan. The cohort comprised 23 participants, stratified by sex and cardiovascular disease (CVD) status (5 per sex/CVD subgroup). This design allows us to: (1) define a baseline “sirtuin profile” of healthy longevity, (2) evaluate the impact of CVD as a prevalent age-related pathology, and (3) explore potential sex-specific modulation. These findings establish an initial human framework linking sirtuin translational control to healthy ageing and cardiovascular health. Full article

Blue Zones (BZs) are regions across the world associated with exceptional human longevity, where individuals routinely live into their 90s and beyond. These areas share distinct lifestyle and environmental factors that promote healthy aging. The established BZs include Sardinia, Okinawa, Ikaria, and Nicoya, while several “emerging” BZs have been reported in various parts of the globe. This study investigates an area in Sicily for similar longevity patterns. Demographic data from the Italy National Institute of Statistics and local civil registries identify the municipality of Caltabellotta, home to approximately 3000 residents, and the nearby Sicani Mountains as a potential emerging BZ. The area exhibits a significantly higher prevalence of nonagenarians and centenarians compared to national and regional averages. Between 1900 and 1924, the proportion of newborns in Caltabellotta who reached age 90 and above rose from 3.6% to 14%, with 1 out of 166 individuals during this period reaching the age of 100. Historical, dietary, environmental, and sociocultural characteristics align with known BZ traits, including adherence to the Mediterranean diet, physical activity through agrarian routines, strong social cohesion, and minimal environmental pollution. A comparative analysis with the validated Sardinia BZ supports the hypothesis that this Sicilian area may represent an emerging longevity hotspot. Further multidisciplinary investigation is warranted to substantiate these findings. Full article

Background: Understanding the multifactorial determinants of human longevity remains a major scientific challenge. Certain regions of the world—so-called “longevity hotspots”—exhibit a notably high prevalence of centenarians; one such region is the province of Ourense, in north-western Spain. Objectives: This study aimed to analyse, for the first time, the nutritional factors associated with healthy longevity among centenarians, as well as those linked to longevity irrespective of health status, in the province of Ourense. Methods: A cross-sectional, retrospective, observational, mixed-methods study was conducted. A population of 261 individuals aged 100 or over residing in Ourense was identified. A sample of 156 participants was included in the quantitative analysis; from this sample, 25 centenarians were selected for in-depth qualitative analysis through personal interviews. Results: Dietary patterns aligned with the Southern European Atlantic Diet (SEAD), combined with strong social bonds and a culture of self-sufficiency, appear to be key contributors to exceptional longevity in this population. Conclusions: Remarkable longevity in Ourense is associated with a combination of factors: adherence to an SEAD-style dietary pattern, an active and uncomplicated lifestyle, and strong social support networks. Full article

The gut microbiota (GM), the set of microorganisms that colonizes our intestinal tract, can undergo many changes, some of which are age related. Several studies have shown the importance of maintaining a healthy GM for a good quality of life. In the elderly, maintaining a good GM may become a real defense against infection by pathogens, such as C. difficile. In addition to the GM, bile acids (BAs) have been shown to provide an additional defense mechanism against the proliferation of pathogenic bacteria and to regulate bacterial colonization of the gut. BAs are molecules produced in the host liver and secreted with the bile into the digestive tract, and they are necessary for the digestion of dietary lipids. In the gut, host-produced BAs are metabolized by commensal bacteria to secondary BAs. In general GM and host organisms interact in many ways. This review examines the relationship between GM, BAs, aging, and possible new approaches such as dietary interventions, administration of ursodesoxycholic acid/tauroursodesoxycholic acid (UDCA/TUDCA), and probiotics to enrich the microbial consortia of the GM in the elderly and achieve a eubiotic state necessary for maintaining good health. The presence of Firmicutes and Actinobacteria together with adequate levels of secondary BAs would provide protection and improve the frailty state in the elderly. In fact, an increase in secondary BAs has been observed in centenarians who have reached old age without serious health issues, which may justify their active role in achieving longevity. Full article

Background: During the last two decades, a limited number of studies have provided echocardiographic details regarding the cardiac structure and function of individuals aged ≥100 years. These studies analyzed limited sample sizes of centenarians using different methodologies. The present systematic review was primarily designed to summarize the main findings of these studies and to examine the overall influence of extremely advanced age on cardiac structure and function. Methods: All echocardiographic studies that evaluated the cardiac structure and function in individuals aged ≥100 years, selected from the PubMed, Embase, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) databases, were included. There was no limitation on the time period. The risk of bias was assessed by using the National Institutes of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Results: A total of eight studies with 1340 centenarians [median age 101.4 years (IQR 101–103 years)] met the eligibility criteria and were analyzed. The centenarians were predominantly females [76.3% (IQR 60–85%)] with a small body surface area, long history of hypertension and slightly impaired renal functional reserve. The centenarian population showed a reduced burden of cardiovascular disease but an increased comorbidity burden, as assessed using the Charlson [median value 3.7 (IQR 1.8–5.5)] and Katz [median value 2.1 (IQR 1.1–3.1)] indexes. The echocardiographic findings comprised left ventricular (LV) concentric remodeling, with first-degree diastolic dysfunction [median E/A ratio 0.8 (IQR 0.7–0.9)], a moderate increase in LV filling pressure [median E/e’ ratio 16.8 (IQR 16.2–17)], normal LV systolic function [median left ventricular ejection fraction (LVEF) 60.9% (IQR 55–84%)] and mild-to-moderate pulmonary hypertension [median systolic pulmonary artery pressure 42.1 mmHg (IQR 37–54 mmHg)]. The pooled prevalence of LV systolic dysfunction (LVEF < 50%) was 15.8%. Moderate-to-severe valvular heart diseases were detected in less than one-third of the centenarians. Compared with the outpatient and in-home cohorts, hospitalized centenarians were less commonly females and were more likely to be affected by significant LV hypertrophy with a supra-normal LVEF, higher degrees of valvulopathies and impaired pulmonary hemodynamics. Conclusions: The evidence currently suggests that centenarians have typical LV concentric remodeling with increased myocardial stiffness and diastolic dysfunction, which predispose them to heart failure with a preserved ejection fraction (HFpEF). Cardioprotective treatment should be considered for personalized implementation and uptitration in this special population. Full article

Frailty refers to a state of increased vulnerability to mortality and other adverse outcomes as a consequence of age-related decline in physiologic reserve and function. Comparative biomedical scientists are relied upon to innovate approaches to enhance understanding of the similarities and differences between humans and other animal species that can impact healthy aging. The research aim of this study was to develop a clinical frailty index (FI) in the Exceptional Aging in Rottweilers Study (EARS) and test its ability to predict all-cause mortality in elderly dogs. EARS is an ongoing lifetime cohort study of pet dogs with extreme longevity living in North America. Living 30% longer than the breed average, these dogs represent the canine counterpart to human centenarians. A 34-item FI (EARS-FI) was constructed to assess deficit accumulation using clinical data collected by telephone interviews with owners of 93 dogs with extreme longevity. Health deficits across multiple domains, including cognitive and sensory, cardiovascular and endocrine, and mobility, were included. The association between EARS-FI and subsequent mortality was tested in Kaplan-Meier survival analysis and in age-adjusted Cox proportional hazard models. Median (interquartile range) EARS-FI was 0.43 (0.38–0.50), and the estimated frailty limit was 0.68, consistent with data reported in humans with extreme longevity. Frailty index increased with increasing chronological age (p < 0.001). Deficit accumulation was significantly associated with increased mortality risk. Age-adjusted hazard ratio for mortality per 0.01 unit increase in FI was 1.05 (95%CI, 1.02–1.08; p = 0.001). This work provides the first demonstration of a strong association between frailty and mortality risk in pet dogs with extreme longevity. Notably, EARS-FI showed key features observed in the evaluation of frailty in aging human populations: heterogeneity, increase with chronological age, and estimated limit of <0.7. Validated here as a predictor of mortality in aged pet dogs, EARS-FI offers a useful tool for further comparative analyses of the linkages between deficit accumulation, mortality, and other adverse health outcomes. Full article

Studying models of healthy aging and exceptional longevity is crucial to understanding a possible longevity signature, as most show resistance to age-related diseases. In particular, semi- and supercentenarians are a highly selected group, having survived significant adversities, including the Spanish flu and COVID-19 pandemics, indicating distinctive immune system characteristics. This paper analyzes the inflammatory scores (INFLA-score, Systemic Inflammation Response Index (SIRI)) and Aging-Related Immune Phenotype (ARIP) indicators calculated from the dataset of the DESIGN project, including 249 participants aged 19–111 years, aiming to understand the immune-inflammatory (IMFLAM) role in achieving longevity. Statistical analyses, including linear regression and one-way ANOVA, were performed to explore the correlations between these parameters and age. Both INFLA-score and SIRI showed a significant increase with age. However, no statistical differences were found when comparing the values of semi- and supercentenarians to other age groups, which are similar to adults and lower than younger centenarians. Regarding ARIP values, it is noteworthy that when comparing the CD8⁺ Naïve/Effector scores between groups, no significant differences were observed between the semi- and supercentenarian group and the other groups. These results support the idea that the control of IMFLAM response can promote extreme longevity. Full article

Small non-coding RNAs (sncRNAs), particularly microRNAs (miRNAs), play an important role in transcriptome regulation by binding to mRNAs and post-transcriptionally inhibiting protein production. This regulation occurs in both physiological and pathological conditions, where the expression of many miRNAs is altered. Previous reports by our group and others have demonstrated that miRNA expression is also altered during aging. However, most studies have analyzed human peripheral blood samples or brain samples from animal models, leaving a gap in knowledge regarding miRNA expression in the human brain. In this work, we analyzed the expression of sncRNAs from coronal sections of human hippocampal samples, a tissue with a high vulnerability to deleterious conditions such as aging. Samples from young (n = 5, 27–49 years old), old (n = 8, 58–88 years old), and centenarian (n = 3, 97, 99, and 100 years old) individuals were included. Our results reveal that sncRNAs, particularly miRNAs, are differentially expressed (DE) in the human hippocampus with aging. Besides, miRNA-mediated regulatory networks revealed significant interactions with mRNAs deregulated in the same hippocampal samples. Surprisingly, 80% of DE mRNA in the centenarian vs. old comparison are regulated by hsa-miR-192-5p and hsa-miR-3135b. Additionally, validated hsa-miR-6826-5p, hsa-let-7b-3p, hsa-miR-7846, and hsa-miR-451a emerged as promising miRNAs that are deregulated with aging and should be further investigated. Full article

Background/Objectives: Outcomes for hip fracture patients have improved over the years, yet the population of older patients (≥80 years) continues to grow. By 2100, the global centenarian population is projected to exceed 25 million, but data on hip fracture outcomes in this group are rare and often derived from small samples. This study aimed to analyze outcomes for centenarian hip fracture patients in specialized geriatric trauma centers and compare them with those of patients under 80. Methods: We conducted a retrospective analysis of the AltersTraumaRegister DGU^® from 2016 to 2022, including all proximal femur fracture data. Patients were categorized into two groups: under 80 years and centenarians. The primary outcome was in-hospital mortality, with secondary outcomes including quality of life, walking ability on postoperative day seven, length of hospital stay, readmission rates, and changes in living situations. Results: Among 14,521 patients, 316 were over 99 years old. In-house mortality was significantly higher in centenarians (15.44% vs. 3.58%; p < 0.001), with more discharged to nursing homes. After matching by the Geriatrics at Risk (GeRi) score, mortality differences diminished. Conclusions: While age is a risk factor for mortality, centenarian hip fracture patients’ outcomes do not significantly differ from those aged ≤80 when considering other risk factors. Full article

In previous studies, using transcriptomic analysis, we observed higher levels of aryl hydrocarbon receptor (AHR) gene expression in the peripheral blood cells of centenarians compared to octogenarians. This suggests the potential significance of this receptor in maintaining physiological balance and promoting healthy aging, possibly linked to its critical role in detoxifying xenobiotics. In our current study, we confirmed that AHR expression is indeed higher in centenarians. We employed C. elegans as a model known for its suitability in longevity studies to explore whether the AHR pathway has a significant impact on lifespan and healthspan. Our survival assays revealed that two different mutants of AHR-1 exhibited lower longevity. Additionally, we used a mouse model to examine whether supplementation with pomegranate extract modulates the expression of AHR pathway genes in the liver. Furthermore, we studied a nutritional strategy based on pomegranate extract administration to investigate its potential modulation of life- and healthspan in worms. Full article

The world is facing a significant demographic transition, with a substantial increase in the proportion of older persons, as well as long-lived persons (especially nonagenarians and centenarians). One of the popular beliefs is that old age is synonymous with disease and disability. However, the successful aging hypothesis suggests that those older persons with advanced chronological age who maintain their functional capacity derive from it a delay in biological aging, enhancing the quality of organic aging and regulation. Therefore, regardless of chronological age, even in cases of extreme longevity, those older adults with a successful aging phenotype and favorable functional capacity would be expected to have satisfactory post-surgical recovery with a low risk of morbidity and mortality. Currently, there is a significant gap between the availability of high-certainty surgical evidence that allows for evidence-based interventions applicable to the long-lived population—taking into account the actual conditioning factors of the health phenotype in older persons—and, above all, predictors of satisfactory post-surgical evolution. The application of meta-research to geriatric surgery emerges as a fundamental tool to address this knowledge gap and reveals opportunities and limitations that need to be resolved in the near future to establish evidence-based surgical care for older persons. The aim of this manuscript was to present a real and globally relevant scenario related to surgical care, addressing the longevity, the availability, and the quality of surgical evidence applicable to this population, and also to present variables to consider in analysis and future perspectives in research and meta-research in geriatric surgery. Full article