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17 pages, 1264 KiB  
Article
An Emerging Longevity Blue Zone in Sicily: The Case of Caltabellotta and the Sicani Mountains
by Alessandra Errigo, Giovanni Mario Pes, Calogero Caruso, Giulia Accardi, Anna Aiello, Giuseppina Candore and Sonya Vasto
J. Ageing Longev. 2025, 5(3), 26; https://doi.org/10.3390/jal5030026 - 30 Jul 2025
Viewed by 212
Abstract
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, [...] Read more.
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
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32 pages, 3472 KiB  
Article
Exploring the Dietary Patterns and Health Behaviours of Centenarians in Ourense (Spain): Adherence to the Southern European Atlantic Diet
by Pablo García-Vivanco, Roberto Fernandez, Rosa Meijide-Faílde, Esperanza Navarro-Pardo, Cristina Conde, Ricardo de la Fuente, Cristina Margusinos, Alberto Rodríguez, Ana Canelada, Pablo Taboada, Alberto Cepeda and Alberto Coelho
Nutrients 2025, 17(13), 2231; https://doi.org/10.3390/nu17132231 - 5 Jul 2025
Viewed by 1231
Abstract
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, [...] Read more.
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
(This article belongs to the Section Nutritional Epidemiology)
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18 pages, 2618 KiB  
Review
Bi-Directional Relationship Between Bile Acids (BAs) and Gut Microbiota (GM): UDCA/TUDCA, Probiotics, and Dietary Interventions in Elderly People
by Emanuele Francini, Gretta V. Badillo Pazmay, Stefania Fumarola, Antonio Domenico Procopio, Fabiola Olivieri and Francesca Marchegiani
Int. J. Mol. Sci. 2025, 26(4), 1759; https://doi.org/10.3390/ijms26041759 - 19 Feb 2025
Viewed by 2463
Abstract
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, [...] Read more.
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
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17 pages, 792 KiB  
Systematic Review
Echocardiographic Assessment of Cardiac Structure and Function of Centenarians: A Systematic Review
by Andrea Sonaglioni, Gian Luigi Nicolosi, Giovanna Elsa Ute Muti-Schünemann, Alessio Polymeropoulos, Michele Lombardo and Paola Muti
Geriatrics 2025, 10(1), 26; https://doi.org/10.3390/geriatrics10010026 - 12 Feb 2025
Viewed by 1145
Abstract
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 [...] Read more.
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
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12 pages, 662 KiB  
Article
Frailty and Mortality Risk Among Dogs with Extreme Longevity: Development and Predictive Validity of a Clinical Frailty Index in the Exceptional Aging in Rottweilers Study
by David J. Waters, Aimee H. Maras, Rong Fu, Andres E. Carrillo, Emily C. Chiang and Cheri L. Suckow
Animals 2024, 14(24), 3651; https://doi.org/10.3390/ani14243651 - 18 Dec 2024
Cited by 1 | Viewed by 1549
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Behavior, Welfare, Health and Care of Aging Pets)
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12 pages, 1857 KiB  
Article
Immune-Inflammatory Response in Lifespan—What Role Does It Play in Extreme Longevity? A Sicilian Semi- and Supercentenarians Study
by Giulia Accardi, Anna Calabrò, Rosalia Caldarella, Calogero Caruso, Marcello Ciaccio, Marta Di Simone, Mattia Emanuela Ligotti, Serena Meraviglia, Rosa Zarcone, Giuseppina Candore and Anna Aiello
Biology 2024, 13(12), 1010; https://doi.org/10.3390/biology13121010 - 4 Dec 2024
Cited by 2 | Viewed by 1652
Abstract
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 [...] Read more.
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
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13 pages, 1906 KiB  
Article
Age-Related sncRNAs in Human Hippocampal Tissue Samples: Focusing on Deregulated miRNAs
by Ainhoa Alberro, Rocío Del Carmen Bravo-Miana, Saioa GS Iñiguez, Andrea Iribarren-López, Marta Arroyo-Izaga, Ander Matheu, Maider Muñoz-Culla and David Otaegui
Int. J. Mol. Sci. 2024, 25(23), 12872; https://doi.org/10.3390/ijms252312872 - 29 Nov 2024
Viewed by 994
Abstract
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 [...] Read more.
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
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12 pages, 571 KiB  
Article
Outcome of Centenarians with Hip Fracture: An Analysis of the Registry for Geriatric Trauma (ATR-DGU)
by Bastian Pass, Matthias Knobe, Hannah Schmidt, Christopher Bliemel, Rene Aigner, Ulrich Liener, Sven Lendemans, Carsten Schoeneberg, Ulf Boekeler and Registry for Geriatric Trauma (ATR-DGU)
J. Clin. Med. 2024, 13(21), 6421; https://doi.org/10.3390/jcm13216421 - 26 Oct 2024
Cited by 1 | Viewed by 1061
Abstract
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 [...] Read more.
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
(This article belongs to the Section Orthopedics)
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12 pages, 4156 KiB  
Article
Involvement of Aryl Hydrocarbon Receptor in Longevity and Healthspan: Insights from Humans, Mice, and C. elegans
by Eva Serna, David Verdú, Alicia Valls, Ángel Belenguer-Varea, Francisco José Tarazona-Santabalbina, Consuelo Borrás and José Viña
Int. J. Mol. Sci. 2024, 25(18), 9943; https://doi.org/10.3390/ijms25189943 - 14 Sep 2024
Viewed by 1960
Abstract
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, [...] Read more.
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
(This article belongs to the Special Issue Health Promoting Benefits of Natural Products and Functional Foods)
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7 pages, 798 KiB  
Perspective
Meta-Research in Geriatric Surgery: Improving the Quality of Surgical Evidence for Older Persons in a Multidimensional-Scale Research Field
by Ivan David Lozada-Martinez, David A. Hernandez-Paez, Isabela Palacios Velasco, Darly Martinez Guevara and Yamil Liscano
J. Clin. Med. 2024, 13(18), 5441; https://doi.org/10.3390/jcm13185441 - 13 Sep 2024
Cited by 2 | Viewed by 1468
Abstract
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, [...] Read more.
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
(This article belongs to the Section General Surgery)
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14 pages, 2847 KiB  
Article
Associations between Brain Alpha-Tocopherol Stereoisomer Profile and Hallmarks of Brain Aging in Centenarians
by Jia Pei Chan, Jirayu Tanprasertsuk, Elizabeth J. Johnson, Priyankar Dey, Richard S. Bruno, Mary Ann Johnson, Leonard W. Poon, Adam Davey, John L. Woodard and Matthew J. Kuchan
Antioxidants 2024, 13(8), 997; https://doi.org/10.3390/antiox13080997 - 17 Aug 2024
Cited by 1 | Viewed by 1910
Abstract
Brain alpha-tocopherol (αT) concentration was previously reported to be inversely associated with neurofibrillary tangle (NFT) counts in specific brain structures from centenarians. However, the contribution of natural or synthetic αT stereoisomers to this relationship is unknown. In this study, αT stereoisomers were quantified [...] Read more.
Brain alpha-tocopherol (αT) concentration was previously reported to be inversely associated with neurofibrillary tangle (NFT) counts in specific brain structures from centenarians. However, the contribution of natural or synthetic αT stereoisomers to this relationship is unknown. In this study, αT stereoisomers were quantified in the temporal cortex (TC) of 47 centenarians in the Georgia Centenarian Study (age: 102.2 ± 2.5 years, BMI: 22.1 ± 3.9 kg/m2) and then correlated with amyloid plaques (diffuse and neuritic plaques; DPs, NPs) and NFTs in seven brain regions. The natural stereoisomer, RRR-αT, was the primary stereoisomer in all subjects, accounting for >50% of total αT in all but five subjects. %RRR was inversely correlated with DPs in the frontal cortex (FC) (ρ = −0.35, p = 0.032) and TC (ρ = −0.34, p = 0.038). %RSS (a synthetic αT stereoisomer) was positively correlated with DPs in the TC (ρ = 0.39, p = 0.017) and with NFTs in the FC (ρ = 0.37, p = 0.024), TC (ρ = 0.42, p = 0.009), and amygdala (ρ = 0.43, p = 0.008) after controlling for covariates. Neither RRR- nor RSS-αT were associated with premortem global cognition. Even with the narrow and normal range of BMIs, BMI was correlated with %RRR-αT (ρ = 0.34, p = 0.021) and %RSS-αT (ρ = −0.45, p = 0.002). These results providing the first characterization of TC αT stereoisomer profiles in centenarians suggest that DP and NFT counts, but not premortem global cognition, are influenced by the brain accumulation of specific αT stereoisomers. Further study is needed to confirm these findings and to determine the potential role of BMI in mediating this relationship. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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10 pages, 230 KiB  
Article
“I Have Never Visited a Health Center”: Ethiopian Centenarians’ Perceptions of Their Health Conditions
by Samson Chane and Margaret E. Adamek
J. Ageing Longev. 2024, 4(3), 264-273; https://doi.org/10.3390/jal4030019 - 6 Aug 2024
Viewed by 1426
Abstract
The global centenarian population is expected to reach 4 million by 2050, yet little is known about the health status of centenarians in Sub-Saharan Africa. A case study examined the health conditions and functionality of nine Ethiopian centenarians. In-depth interviews revealed that all [...] Read more.
The global centenarian population is expected to reach 4 million by 2050, yet little is known about the health status of centenarians in Sub-Saharan Africa. A case study examined the health conditions and functionality of nine Ethiopian centenarians. In-depth interviews revealed that all nine were Orthodox Christians and lived with extended family; eight were male. Aside from minor health complaints, centenarians in rural Ethiopia perceived that their sensory/cognitive functionality was normal until their late 90s. Despite a lack of medical care, the centenarians included two survivors, four delayers, and three escapers. Centenarians in rural Ethiopia were embedded in closely knit, religious, multigenerational households and communities and aspired to live resiliently. These findings call for the consideration of the unique health status of centenarians in Global South nations in their own cultural context. Full article
17 pages, 2958 KiB  
Article
Whole-Exome Analysis for Polish Caucasian Patients with Retinal Dystrophies and the Creation of a Reference Genomic Database for the Polish Population
by Ewa Matczyńska, Robert Szymańczak, Katarzyna Stradomska, Przemysław Łyszkiewicz, Maria Jędrzejowska, Karolina Kamińska, Marta Beć-Gajowniczek, Ewa Suchecka, Marek Zagulski, Marta Wiącek, Edward Wylęgała, Anna Machalińska, Małgorzata Mossakowska, Monika Puzianowska-Kuźnicka, Sławomir Teper and Anna Boguszewska-Chachulska
Genes 2024, 15(8), 1011; https://doi.org/10.3390/genes15081011 - 1 Aug 2024
Viewed by 2077
Abstract
We present the results of the first study of a large cohort of patients with inherited retinal dystrophies (IRD) performed for the Polish population using whole-exome sequencing (WES) in the years 2016–2019. Moreover, to facilitate such diagnostic analyses and enable future application of [...] Read more.
We present the results of the first study of a large cohort of patients with inherited retinal dystrophies (IRD) performed for the Polish population using whole-exome sequencing (WES) in the years 2016–2019. Moreover, to facilitate such diagnostic analyses and enable future application of gene therapy and genome editing for IRD patients, a Polish genomic reference database (POLGENOM) was created based on whole-genome sequences of healthy Polish Caucasian nonagenarians and centenarians. The newly constructed database served as a control, providing a comparison for variant frequencies in the Polish population. The diagnostic yield for the selected group of IRD patients reached 64.9%. The study uncovered the most common pathogenic variants in ABCA4 and USH2A in the European population, along with several novel causative variants. A significant frequency of the ABCA4 complex haplotype p.(Leu541Pro; Ala1038Val) was observed, as well as that of the p.Gly1961Glu variant. The first VCAN causative variant NM_004385.5:c.4004-2A>G in Poland was found and described. Moreover, one of the first patients with the RPE65 causative variants was identified, and, in consequence, could receive the dedicated gene therapy. The availability of the reference POLGENOM database enabled comprehensive variant characterisation during the NGS data analysis, confirming the utility of a population-specific genomic database for enhancing diagnostic accuracy. Study findings suggest the significance of genetic testing in elder patients with unclear aetiology of eye diseases. The combined approach of NGS and the reference genomic database can improve the diagnosis, management, and future treatment of IRDs. Full article
(This article belongs to the Special Issue Genetics of Eye Development and Diseases)
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18 pages, 2718 KiB  
Article
Markers of Mitochondrial Function and DNA Repair Associated with Physical Function in Centenarians
by Ines Sanchez-Roman, Beatriz Ferrando, Camilla Myrup Holst, Jonas Mengel-From, Signe Hoei Rasmussen, Mikael Thinggaard, Vilhelm A. Bohr, Kaare Christensen and Tinna Stevnsner
Biomolecules 2024, 14(8), 909; https://doi.org/10.3390/biom14080909 - 26 Jul 2024
Viewed by 2606
Abstract
Mitochondrial dysfunction and genomic instability are key hallmarks of aging. The aim of this study was to evaluate whether maintenance of physical capacities at very old age is associated with key hallmarks of aging. To investigate this, we measured mitochondrial bioenergetics, mitochondrial DNA [...] Read more.
Mitochondrial dysfunction and genomic instability are key hallmarks of aging. The aim of this study was to evaluate whether maintenance of physical capacities at very old age is associated with key hallmarks of aging. To investigate this, we measured mitochondrial bioenergetics, mitochondrial DNA (mtDNA) copy number and DNA repair capacity in peripheral blood mononuclear cells from centenarians. In addition, circulating levels of NAD+/NADH, brain-derived neurotrophic factor (BDNF) and carbonylated proteins were measured in plasma and these parameters were correlated to physical capacities. Centenarians without physical disabilities had lower mitochondrial respiration values including ATP production, reserve capacity, maximal respiration and non-mitochondrial oxygen-consumption rate and had higher mtDNA copy number than centenarians with moderate and severe disabilities (p < 0.05). In centenarian females, grip strength had a positive association with mtDNA copy number (p < 0.05), and a borderline positive trend for activity of the central DNA repair enzyme, APE 1 (p = 0.075), while a negative trend was found with circulating protein carbonylation (p = 0.07) in the entire cohort. Lastly, a trend was observed for a negative association between BDNF and activity of daily living disability score (p = 0.06). Our results suggest that mechanisms involved in maintaining mitochondrial function and genomic stability may be associated with maintenance of physical function in centenarians. Full article
(This article belongs to the Special Issue Mechanisms and Novel Biomarkers Underlying Aging and Longevity)
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26 pages, 3853 KiB  
Article
Female Rat Behavior Effects from Low Levels of Hexavalent Chromium (Cr[VI]) in Drinking Water Evaluated with a Toxic Aging Coin Approach
by Samuel T. Vielee, Jessica Isibor, William J. Buchanan, Spencer H. Roof, Maitri Patel, Idoia Meaza, Aggie Williams, Jennifer H. Toyoda, Haiyan Lu, Sandra S. Wise, J. Calvin Kouokam, Jamie Young Wise, AbouEl-Makarim Aboueissa, Jun Cai, Lu Cai and John P. Wise
Appl. Sci. 2024, 14(14), 6206; https://doi.org/10.3390/app14146206 - 17 Jul 2024
Cited by 2 | Viewed by 1563
Abstract
We are facing a critical aging crisis, with geriatric populations (65+) growing to unprecedented proportions and ~4 million people (a 6.5-fold increase) expected to become centenarians by 2050. This is compounded by environmental pollution, which affects individuals of all ages and contributes to [...] Read more.
We are facing a critical aging crisis, with geriatric populations (65+) growing to unprecedented proportions and ~4 million people (a 6.5-fold increase) expected to become centenarians by 2050. This is compounded by environmental pollution, which affects individuals of all ages and contributes to age-related diseases. As we have a limited understanding of how environmental pollutants affect older populations distinctly from younger populations, these longer-lived geriatric populations present a key knowledge gap. To address this knowledge gap, we employ a “Toxic Aging Coin” approach: heads consider how age impacts chemical toxicity, and tails consider how chemicals act as gerontogens—or how they accelerate biological aging. We employed this approach to investigate hexavalent chromium (Cr[VI]) impacts on female rats exposed to 0.05 or 0.1 mg Cr(VI)/L in drinking water for 90 days; these are the maximum contaminant levels (i.e., the highest levels permitted) from the World Health Organization and U.S. Environmental Protection Agency, respectively. During exposure, rats performed a battery of behavior assays to assess grip strength, locomotor coordination, anxiety, spatial memory, sociability, and social novelty preference. We observed age differences in Cr(VI) neurotoxicity, with grip strength, locomotor function, and spatial memory in middle-aged females being particularly affected. We further compared these results in females to results in males, noting many sex differences, especially in middle-aged rats. These data emphasize the need to consider age and sex as variables in toxicology and to revisit drinking water regulations for Cr(VI). Full article
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