Centenarians exhibit remarkable longevity and compression of morbidity making them an ideal population for uncovering proteins associated with successful aging. Using proteomics, we characterized the immune and cardiometabolic profiles of centenarians' plasma from the SWISS100 cohort. We identified 583 differentially expressed proteins (DEPs) by centenarians when compared with hospitalized geriatric patients (age 80-90 years) and younger healthy participants (age 30-60 years). We replicated the association of 23 proteins with a standard set of aging proteins (APs) developed by the Targeting Aging with Metformin (TAME) consortium. By comparing the centenarian signature to an independent centenarian proteomics study, we identified 135 DEPs in both studies with identical aging directions, establishing a robust set of APs in centenarians. Applying fractional polynomial regressions, we uncovered proteins with linear and non-linear profiles associated with age and identified a subgroup of 37 proteins with a younger signature in centenarians. Protein-protein interaction and pathway enrichment analyses of 37 proteins point to programmed cell death, metabolic enzyme pathways, regulation of extracellular matrix stability, immune and inflammatory responses, and neurotrophic signaling pathways. This novel approach to aging research has uncovered new proteins and pathways, which may present promising targets to understand processes associated with longevity and healthy aging.

Background/Objectives: Clinically overt Alzheimer's disease (AD) is associated with significant changes in personality factors. Earlier studies indicated that personality factors do not remain stable in elderly controls. Whether the early presence of AD neuroimaging markers may predict subsequent changes in personality factors is still debatable. Methods: To address this issue, we examined the association between Big Five factor scores and baseline AD and vascular imaging markers in a previously established cohort of 58 elderly controls with a 4.5-year follow-up. Personality was assessed with the Neuroticism-Extraversion-Openness Personality Inventory-Revised scale at inclusion and 55-month follow-up. Regression models were used to identify predictors of personality factor changes including time, age, sex, APOE epsilon 4 allele, baseline MMSE scores, amyloid PET positivity, abnormal FDG-PET patterns, mesial temporal lobe atrophy and Fazekas scores, and number of microbleeds. Results: In both univariate and multivariable models, the decrease in openness was related to abnormal FDG PET patterns. This single variable explained 15% of the variance of this personality factor. In univariate models, lower MMSE scores and amyloid positivity at baseline were associated with a subsequent decrease in agreeableness scores. In multivariable models, these two parameters explained 11% and 8% of variance respectively. The other personality factors were not associated with AD and cerebrovascular imaging markers. Conclusions: Personality patterns at baseline may impact the emergence of AD pathology but they may also change rapidly as a function of the presence of early AD-related PET abnormalities.

Altercentric and egocentric biases (AB, EB) refer to the impact of another agent’s/own perspective on the speed with which one can report one’s own/another visual perspective respectively. These biases are known to be affected by illnesses and in particular borderline personality (BPD). Coupling the dot-perspective taking task with high-density EEG recordings at the surface and in the inverse space, we analyzed the regional distribution of neural generators related to AB and EB in healthy controls (n = 24) and forensic BPD male patients (n = 14) making comparisons with previous functional MRI data obtained with the same experimental design. In both controls and BPD cases, AB was associated with early EEG activations of visual association areas. In contrast, EB was related to increased use of neural sources in salience, mentalizing networks and mirror neuron areas bilaterally. In forensic BPD patients, no statistically significant differential activation of neural generators was observed in respect to this variable. Our preliminary findings in a small sample of BPD patients show that unlike fMRI observations that pointed to an AB-related widespread increase of BOLD signal in central executive and mentalizing areas, this was not the case at the level of neural generators. Paralleling previous fMRI data, EB was related to increased need of activation of neural sources in visual association areas and later on in several networks involved in social cognition. Such activation was not observed in forensic BPD cases supporting the hypothesis of a decreased ability of these patients in mobilizing their brain resources when treating the Self-Other discrepancy. However, the limited statistical power and post-hoc group-level interaction analysis point to the need for further confirmatory analyses of these first experimental evidences.

Tracking the evolution of scientific knowledge is challenging due to the scale and complexity of the biomedical literature. Neurosyphilis is a clinically complex and historically stigmatized condition that remains difficult to diagnose and manage. Its underexplored literature offers an ideal test case to evaluate digital methods for mapping research trends and identifying knowledge gaps. We aim to assess how large language models (LLMs), network analysis, and interrupted time series analysis (ITSA) can be combined to automate literature classification and examine how knowledge of neurosyphilis has evolved. We systematically searched Web of Science, Embase, PubMed Central, the Cochrane Library, and Lens for records on neurosyphilis published until December 31, 2024. We included records with available titles and abstracts in which GPT-4o mini was identified as being focused primarily on syphilis or neurosyphilis. Eligible records were classified into 23 research fields via LLM-based prompts. Network analysis visualized changes in research structures over time, and the ITSA assessed associations between publication trends and major clinical or technological milestones. Among the 14 934 retrieved records, 4 646 met the inclusion criteria. LLM-based classification showed high repeatability (agreement = 99·67

OBJECTIVE:To analyse the prevalence of depressive symptoms in centenarians, identify their predictors, and explore the role of functional dependence as a contributing factor. DESIGN SETTING, AND PARTICIPANTS:Cross-sectional baseline data from the Swiss Centenarian Study (n = 102), including community-dwelling and institutionalised participants with complete data on depressive symptoms and functional capacity. MEASUREMENTS:Functional capacity was assessed using the Older Americans Resources and Services Multidimensional Functional Assessment Questionnaire. Depressive symptoms were measured with the Geriatric Depression Scale - Short Form. Group differences were analysed using Chi-squared tests; relationships were examined with correlations. Multiple linear regressions identified predictors. Mediation analysis explored the interplay between functional capacity, living situation, and depressive symptoms. RESULTS:Functional capacity varied, with basic activities of daily living generally better preserved than instrumental activities. Almost one-fourth of participants screened positive for possible clinical depression, which was significantly more common among institutionalised centenarians (p < .05). Health conditions, anxiety, and lower functional capacity were significant predictors of depressive symptoms and together explained 24.7 % of the variance, with anxiety being the strongest predictor followed by health conditions and functional capacity. Mediation analysis showed that functional capacity mediated the relationship between living situation and depressive symptoms, highlighting its critical role in mental health. CONCLUSIONS:A significant proportion of centenarians screened positive for depression, underscoring the need for greater attention to depressive symptoms and systematic screening. Targeted interventions promoting functional independence may play an important role to prevent depression, and strategies are needed to encourage institutionalised very old individuals to re-develop and maintain a certain level of independence.

Background:Handgrip strength (HGS) is a key diagnostic tool for sarcopenia, yet the comparative prognostic value of the hydraulic dynamometer and pneumatic vigorimeter in hospitalized older adults remains unclear. This study is the first to examine the vigorimeter as a predictor of in-hospital mortality in this setting. Methods:This prospective cohort study included 376 hospitalized older adults (mean age: 82.7 years) across acute, rehabilitation, and long-term care wards. HGS was assessed using both the dynamometer and vigorimeter, applying two sets of cut-offs per instrument. Sarcopenia was confirmed using bioelectrical impedance analysis to calculate the fat-free mass index (FFMI), with four diagnostic criteria combining HGS and FFMI thresholds. Associations between HGS, sarcopenia, and mortality were evaluated using logistic regression and Cox proportional hazards models, with Kaplan-Meier curves illustrating survival differences. Results:Higher HGS measured by the vigorimeter was independently associated with reduced in-hospital mortality (OR 0.96, 95% CI 0.93-0.98, p = 0.001), whereas no significant association was found for dynamometer-measured HGS. Confirmed sarcopenia was significantly associated with mortality for two diagnostic criteria (criterion 2: vigorimeter with DO-HEALTH1 cut-offs: OR 1.77, 95% CI 1.01-3.10, p = 0.047; criterion 4: vigorimeter with DO-HEALTH2 cut-offs: OR 1.76, 95% CI 1.01-3.07, p = 0.048), although no significant association was observed with time-to-mortality. Kaplan-Meier curves demonstrated significant survival differences only for vigorimeter-based HGS cut-offs (p = 0.04). Male sex and falls during hospitalization were associated with increased mortality, while admission to rehabilitation or long-term care wards was associated with reduced mortality. Conclusion:Vigorimeter-based HGS, especially using DO-HEALTH1 cut-offs, demonstrated superior prognostic value for in-hospital mortality compared to the dynamometer. These findings support the clinical utility of the vigorimeter for risk stratification and care planning in hospitalized older adults, particularly in settings where subtle neuromuscular deficits may influence outcomes.

People tend to consider others' perspective when judging their own (altercentric interference, AI) or other (egocentric interference, EI) divergent views. Borderline (BDL) and antisocial personalities are associated with significant changes in EI and AI. Combining the dot perspective-taking task with high-density EEG recordings, our study explores the correlations between EI and AI in cases with BDL diagnosis and court-ordered measures (BDL-COM; n = 14) compared to age-matched healthy controls (n = 24). In Inconsistent trials, controls displayed significant activation of brain generators, which was absent in BDL-COM patients. For the Self-Inconsistent stimuli (altercentric bias), controls showed increased activity in the left superior frontal gyrus between 58 and 74 ms and the left inferior frontal gyrus between 279 and 303 ms. Similar differences were observed for Other-Inconsistent stimuli (egocentric bias) in the precentral gyri and inferior frontal gyrus between 274 and 296 ms. These findings suggest that AI involves an early activation of brain generators in central executive and mentalizing areas. EI is associated with an increased activation of the mirror neuron system based on self-other distinction. These EEG data indicate that BDL-COM patients display significant difficulties activating all of the brain generators involved in the processing of conflicting viewpoints in visual perspective-taking.

Low skeletal mass, often present at hospital admission, has been associated with poor prognoses. To explore the association between computed tomography (CT)-derived skeletal muscle mass at the lumbar level and short- and long-term mortality in critically ill patients. Following PRISMA 2020 guidelines, we included studies on critically ill adults (≥ 18 years) hospitalized in intensive care units (ICU) that measured CT-derived skeletal muscle mass at the lumbar vertebral level within ± 7 days of ICU admission. The primary outcome was mortality, categorized as short-term (including ICU, hospital, 28- and 30-day mortality) and long-term (> 30 days) mortality. MEDLINE and Embase databases were searched without date restrictions. Study screening was performed using Rayyan, data extraction was guided by a custom-designed tool, and quality assessment was performed using the JBI Cohort Study Checklist. A meta-analysis was conducted, focusing on studies that reported short- and long-term mortality among patients with preserved and reduced skeletal muscle. A prevalence meta-analysis was also performed for studies that reported the size of subgroups with low muscle mass. Out of 1248 unique records, 35 studies met the inclusion criteria, involving 9366 participants. The majority were retrospective, single-centre studies conducted on four continents and included heterogeneous populations such as patients with sepsis, COVID-19 and trauma. Sample sizes ranged from 36 to 939, with a wide age range, from 40 to 70 s, and a predominance of male patients (62

Background/Objectives: The prevalence of diabetes in very old people is rising sharply worldwide, due not only to obesity, nutritional and sedentary lifestyles, but also to aging per se. Diabetes is associated with a higher incidence of sarcopenia, malnutrition and physical disabilities. However, many age-specific issues in the clinical management of very old diabetic patients remain unstudied. Methods: This is a case–control prospective study including 162 very old hospitalized diabetic patients and 301 controls. We explored the impact of diabetes on the prevalence of sarcopenia according to the EWGSOP2 criteria, using Jamar handgrip to assess muscle strength, BIA-derived fat-free mass index to assess muscle mass, and the timed up and go test to assess physical performance. We also explored factors associated with sarcopenia in both groups in multiple logistic analysis. Results: Mean age was 84.8 ± 6.0 years. We found a prevalence of sarcopenia of 8.0% and 16.7% in the diabetic and the control groups, respectively (p = 0.010). BMI was independently associated with sarcopenia in both groups, explaining 25% of the model in the diabetic group and 33% of the model in the control group. Conclusions: Sarcopenia was less prevalent in diabetic hospitalized older patients than in other patients, indicating that old frail patients are not the same patients as those that are in epidemiological studies on sarcopenia in diabetes. These results should be confirmed in further studies.

IntroductionHippocampal volume loss occurs physiologically with age, but an accelerated rate of volume loss is linked to neurodegenerative diseases. While evidence suggests that cross-sectional study designs tend to underestimate hippocampal atrophy rates compared to longitudinal approaches, few studies have directly examined the relationship between these two methods in the context of brain aging. This study aims to investigate the association between baseline hippocampal z-scores and hippocampal volume loss over time in a cohort of healthy older adults.Methods182 healthy elderly subjects (mean age: 73.4 ± 3.5 years) who underwent structural Magnetic resonance imaging (MRI) at two timepoints (mean time between the scans 4.8 ± 1.0 years) were included. A subset of participants (n = 103) also completed Positron emission tomography (PET) amyloid imaging. Hippocampal volumes were measured at baseline and follow-up using FreeSurfer (v7.1.1). Baseline volumes were adjusted for age and intracranial volume (ICV) and converted into z-scores. The annualized percent change (APC) in hippocampal volume was calculated for each participant. Neuropsychological assessments were conducted at baseline, 18, and 54 months, and APOE genotyping was performed. Correlation analyses examined the relationship between baseline hippocampal volumes and APC, while multiple regression models explored potential influencing factors.ResultsHippocampal volumes decreased from baseline to follow-up [mean APC (SD): right −1.34% (0.94), left: −1.79% (1.00)]. Small, but statistically significant positive correlations were found between baseline hippocampal z-scores and APC of hippocampal volumes over time, indicating that the lower the volume at baseline, the greater the atrophy rate to timepoint two (right hippocampus: r = 0.17, p = 0.01; left hippocampus: r = 0.14, p = 0.03). No covariates significantly influenced this association (p > 0.05).ConclusionLower baseline hippocampal z-scores are associated with a greater rate of hippocampal atrophy to the follow-up examination. If validated in larger cohorts, these findings could help establish cut-off values for pathological atrophy in cross-sectional studies.

BackgroundThe reduction of violence risk and crime recidivism is the core marker of progress in forensic psychiatry treatment for mentally disordered offenders, and commonly used to decide upon discharge from prison-based security clinics. While dynamic risk is expected to relate to treatment progress, static risk is expected to predict discharge from prison-based treatments. Integrated risk-protection assessment is thought to facilitate prediction of treatment outcome.MethodsIn a two-year prospective observational cohort study using a repeated measures design, we monitored treatment as usual induced changes in violence and protective factors, in 117 offenders of a medium-security forensic clinic in Switzerland. Mixed-effects and multinomial logistic regression models were used to predict longitudinal risk and protection evolution, length of stay, and discharge locations.ResultsForensic psychiatry treatment was indeed associated with decrease in dynamic risk and enhanced protection, contrary to static risk. After 18-24 months of treatment, protective factors counterbalanced risk factors. For risk, both a numeric scale and a structured professional judgement approach equally showed significant improvement over time. For protection and integrated risk-protection, structured professional judgement ratings failed to show significant treatment-related change. Discharge to low-security psychiatry wards was predicted only by favorable baseline risk, protection, and integrated risk-protection, but not by their treatment-related evolution. Longer length of stay was predicted by higher baseline total risk only.ConclusionsStudy results confirm the need to distinguish dynamic from static risk in forensic psychiatric treatment monitoring, and to include integrated risk-protection measures. Treatment length and discharge are predicted by the offenders' baseline risk profile, but not by the evolution of risk and protection factors. A structured professional judgment approach in risk and protection assessment leads to different longitudinal results than the use of numeric scale scores.

IntroductionThe comprehensive geriatric assessment (CGA) is recommended for assessing frailty in older cancer patients but is time-consuming. The G8 screening tool was developed to select frail patients requiring CGA to optimize resources. The Edmonton Frail Scale (EFS) is another frailty scale validated for preoperative frailty screening, but scarcely studied in the field of oncogeriatrics. In this study, we examined the added value of the EFS in older cancer patients already considered as frail by the G8, by analyzing the association of EFS with CGA adjusted for age, gender, metastatic stage and comorbidity. We also analyzed the association of EFS with the one-year mortality rate after adjusting for cancer type and metastatic stage.MethodologyThis retrospective study included patients aged over 70 years old with a new diagnosis of cancer, considered as potentially frail according to the G8 and who had had a CGA (N = 380).ResultsThe EFS identified 329 (86.58%) patients as frail and having a statistically significant predicted number of pathological components on the CGA (r = 0.64, p < 0.001). When adjusted for age, sex, comorbidity, and metastatic stage, the EFS was independently associated with the CGA (p < 0001), as well as with comorbidity (p = 0.004). The patients who died in the first year (43%) had a significantly higher mean EFS score (8/17) than living patients (6/17) (p < 0.0001). After adjustment for cancer type and stage, EFS independently predicted one-year mortality (OR 1.17; 95% CI 1.08–1.28; pseudo R2 = 0.228, p < 0.001).DiscussionThe EFS is a reliable tool for predicting frailty identified by the CGA in an older cancer population pre-selected as frail by the G8. EFS is an independent predictor of one-year mortality after adjustment for confounding factors. Validation of the EFS as a screening tool for frailty in cancer requires further studies to assess its performance in patients with normal G8 scores.

IntroductionWide use of facemasks is one of the many consequences of the COVID-19 pandemic.MethodsWe used an established working memory n-back task in functional magnetic resonance imaging (fMRI) to explore whether wearing a KN95/FFP2 facemask affects overall performance and brain activation patterns. We provide here a prospective crossover design 3 T fMRI study with/without wearing a tight FFP2/KN95 facemask, including 24 community-dwelling male healthy control participants (mean age ± SD = 37.6 ± 12.7 years) performing a 2-back task. Data analysis was performed using the FSL toolbox, performing both task-related and functional connectivity independent component analyses.ResultsWearing an FFP2/KN95 facemask did not impact behavioral measures of the 2-back task (response time and number of errors). The 2-back task resulted in typical activations in working-memory related areas in both MASK and NOMASK conditions. There were no statistically significant differences in MASK versus NOMASK while performing the 2-back task in both task-related and functional connectivity fMRI analyses.ConclusionThe effect of wearing a tight FFP2/KN95 facemasks did not significantly affect working memory performance and brain activation patterns of functional connectivity.

OBJECTIVES:Dementia significantly impacts quality of life, health care costs, and caregiver burden, being a leading cause of death among older adults. We investigated predictors of mortality in people with severe behavioral and psychological symptoms of dementia (BPSD). DESIGN:A multicentric longitudinal observational study was conducted, comprising clinical assessments at baseline and every 6 months for 3 years. SETTING AND PARTICIPANTS:People with severe BPSD (Neuropsychiatric Inventory, NPI ≥32) living at home. METHODS:Data on demographics and clinical characteristics were collected at baseline and during 6-monthly follow-ups over 3 years. The main outcome was mortality, documented over a total period of 4 years and analyzed using the Cox proportional hazards model. RESULTS:Of the 508 patients with dementia with severe BPSD, 165 (32.5%) died during the 4-year follow-up. Non-survivors were older (79.8 ± 7.7 vs 77.3 ± 8.0; P < .001), more likely to be male (58.8% vs 38.5%; P < .001), and had higher BPSD severity (NPI: 57.2 ± 20.2 vs 50.3 ± 17.9; P < .001), lower cognitive function according to the Mini-Mental State Examination (MMSE) (13.5 ± 6.6 vs 16.4 ± 5.9; P < .001), and worse functional status according to the Alzheimer's Disease Cooperative Study - Activities of Daily Living Scale (ADCS) (28.8 ± 16.4 vs 36.3 ± 17.2; P < .001) at baseline. Significant predictors of mortality included male sex [hazard ratio (HR), 2.03; 95% confidence interval (95% CI), 1.46-2.82; P < .001], older age at diagnosis (HR, 1.05; 95% CI, 1.03-1.07; P < .001), higher NPI scores (HR, 1.01; 95% CI, 1.01-1.02; P = .002), lower MMSE (HR, 0.95; 95% CI, 0.93-0.98; P = .001), lower ADCS (HR, 0.98; 95% CI, 0.98-0.99; P = .015), and lower quality of life rated by proxy (HR, 0.97; 95% CI, 0.95-0.99; P = .021). The use of antidepressants (HR, 0.69; 95% CI, 0.48-0.98; P = .038) was associated with increased survival. Delusions (HR, 1.0; 95% CI, 1.03-1.12; P < .001), hallucinations (HR, 1.07; 95% CI, 1.02-1.11; P = .002), and agitation/aggression (HR, 1.05; 95% CI, 1.01-1.09; P = .021) were significantly linked to increased mortality. CONCLUSIONS AND IMPLICATIONS:Older age, male sex, severe BPSD, and lower cognitive and quality of life scores significantly predict increased mortality in patients with severe BPSD.

BackgroundCourt-ordered forensic psychiatry treatments (COT) are specifically designed to reduce the risk of violence in mentally disordered offenders. Given their high costs and ethical issues, mental health professionals need admission criteria to be able to select those candidates with optimal benefit. This study analyses offender-related and treatment-related determinants of COT outcome and risk mitigation.MethodsThis two-year longitudinal study assessed the evolution of 117 adult offenders admitted to a specialized medium-security forensic psychiatry clinic. Treatment outcome included court-ordered discharge locations and the Historical Clinical Risk Management (HCR) score evolution. Treatment progress was assessed every six months across five time-points including measures of protective factors, work rehabilitation and security. Outcome determinants included psychiatric diagnosis and type of offence.ResultsDischarge locations are predicted by pre-treatment risk level. Lower HCR scores are associated with discharge into low-security psychiatry wards independently of the psychiatric diagnosis. Risk reduction follows diagnosis-specific and offense-related patterns and reveals that mentally disordered offenders with Cluster B personality disorders or those sentenced for drug crimes are significantly less prone to benefit from COT.ConclusionsOur findings indicate that criminological characteristics at baseline as well as diagnosis of personality disorders are the main determinants of treatment outcome in our care setting. Inmates with concomitant higher violence risk at baseline and presence of Cluster B personality disorders might benefit the least from court-ordered forensic inpatient psychiatric care in prison.

Significant reduction of repetitive motor neuron discharges (repMNDs) in short-interval intracortical inhibition (SICI) may result from the suppression of later I-waves and mediate the inhibition of motor-evoked potential (MEP). There is no change in the number of repMNDs in intracortical facilitation (ICF). There was a significant variability in SICI and ICF in healthy subjects.

Purpose: To assess the long-term efficacy and safety of treatments for cystoid macular edema in birdshot retinochoroïditis. Methods: Observational retrospective study of 142 HLA-A29-positive patients with cystoid macular edema; the main outcome was the optical coherence tomography intraretinal cysts resolution. Results: During the mean follow-up of 75 months (12–178), 61.3% of patients were successfully treated using 1 to 3 treatment steps, while the others needed more steps. At 6 months, there were no significant effects on ME for anti-TNF (tumor necrosis factor) and IVIg (immunoglobulin) in contrast to antimetabolites (OR 1.98), systemic GCS (glucocorticosteroids), CsA (cyclosporine A) and tocilizumab (odds ratio closed to 2.7), intraocular injected GCS (odds ratio of 4.2), and interferon (odds ratio of 4.4). The percentages of therapeutic success trend to decrease from the initial three treatment steps to the subsequent treatment steps, for systemic GCS (84% to 70%), for anti-TNF (42% to 33%), and for CsA (71% to 33%); the success percentages did not decrease for injected GCS (83% to 89%). Macular edema recurrence occurred with the highest percentage for injected GCS (86.8%, P = 0.01) and the lowest for tocilizumab (10.5%, P = 0.001). Interferons-α and tocilizumab were associated with the lowest prednisone daily doses. Conclusion: The classical uveitic cystoid macular edema therapeutic algorithm could be adapted to birdshot retinochoroïditis.

Abstract With increasing numbers of centenarians world-wide, quality of life in these very old individuals has become a topic of high interest, expanding prior biomedical research. Switzerland is not only among the countries with very high life expectancy but is also among the leading countries in terms life satisfaction. In the present study, we investigated the levels and predictors of life satisfaction in Swiss centenarians. The present analysis included a total of 148 centenarians of the SWISS100 Main Study (Mage = 101.8; range: 100-106; 74.3% female). After identification through the national address registry, centenarians were visited for in-person interviews. Centenarians’ health was quite limited: they had an average of six health issues and over half of them lived in care facilities (57.4%). Their cognitive level was moderate to high. Most were widowed, 84% had children, and they reported a substantial number of social contacts. The majority of centenarians (82.4 %) were satisfied with their lives. Correlations indicated that sociodemographic and health variables had only few associations with life satisfaction, but that psychological aspects including optimistic outlook and meaning in life showed notable links. A regression analysis combining significant variables from domain-specific regressions revealed that optimistic outlook was the strongest predictor of interindividual differences in life satisfaction, followed by meaning in life. In sum, findings highlight that Swiss centenarians present poor levels of health yet manage to maintain high life satisfaction through psychological mechanisms, suggesting high resilience in these very old individuals, which replicates and extends results from prior centenarian studies.