Heike Annette Bischoff-Ferrari

Maximizing healthspan, the period of life spent in good health, is a public health priority. This review aimed to summarize the current evidence from randomized controlled trials on interventions that can prolong healthspan in humans. The specific focus was on multidimensional person-centered outcomes, which reflect functioning rather than disease, such as intrinsic capacity and quality of life. This review was registered (CRD420251015780) and conducted with adherence to the PRISMA guidelines. MEDLINE, EMBASE, and grey literature were systematically searched for studies evaluating interventions that improve intrinsic capacity or quality of life. The search included articles published up to October 16, 2025. Of 1960 publications identified, 15 articles (4656 participants) met the inclusion criteria. There was high heterogeneity between the included studies in terms of the interventions examined, which varied from exercise alone (7 studies) to multidomain interventions (6 studies, all of which included an exercise component), daily oral supplementation (2 studies), or caloric restriction (1 study). Overall, 11 studies reported that exercise or multidimensional intervention (which included an exercise component) improved intrinsic capacity and quality of life. However, due to the small number of studies and heterogeneity, no conclusion could be drawn regarding other interventions. Therefore there is some evidence that exercise could extend intrinsic capacity and quality of life, either aerobic or resistance training alone, or a combination of different types of exercise; but further research is required to evaluate the effect of other interventions that may prolong healthspan across more diverse populations.

Objective: Dysnatremia is the most common electrolyte abnormality detected during hospitalizations and outpatient visits and is associated with adverse outcomes in older adults. However, data on its prevalence and incidence in community-dwelling older individuals remain limited. This study aimed to estimate the prevalence and incidence of dysnatremia in this population across 5 European countries (Austria, France, Germany, Portugal, and Switzerland). Design: Observational analysis of DO-HEALTH, a 3-year multicenter clinical trial including 2157 community-dwelling, generally healthy adults aged 70 years and older. Methods: Sodium blood levels were collected at baseline, 12, 24, and 36 months. Dysnatremia was defined as sodium levels 145 mmol/L (hypernatremia). Baseline prevalence and 3-year incidence were estimated overall and by predefined subgroups based on sex, age, country of residence, body mass index, prevalent chronic conditions, polypharmacy, and use of thiazide-like diuretics. Results: At baseline, 2141 participants (99.3%) had available sodium data. The prevalence of dysnatremia was 3.4% (2.4% hyponatremia; 1.0% hypernatremia), with higher prevalence in participants aged ≥75 years (4.8%) and those using thiazide or thiazide-like diuretics (5.4%). Over 3 years, 150 participants (7.0%) experienced at least 1 episode of dysnatremia (3.8% hyponatremia; 3.2% hypernatremia). Higher incidence of dysnatremia was observed among participants living in Switzerland, using thiazide or thiazide-like diuretics, and with prevalent dysnatremia at baseline. Conclusions: Dysnatremia, previously linked to adverse outcomes in older adults, was observed in a non-negligible proportion of generally healthy, community-dwelling older individuals. These findings provide valuable epidemiologic data and identify subgroups that may warrant closer clinical attention.

Background: The prognostic relevance of perioperative myocardial injury/infarction (PMI) in older patients undergoing major noncardiac surgery remains unclear, as high comorbidity burden may lessen its impact. Methods: Older patients (defined as age ≥70 years with ≥3 comorbidities, or ≥80 years) enrolled in a multicentre, prospective study of patients at increased cardiovascular risk undergoing major noncardiac surgery were analysed. The primary endpoint, all-cause mortality at 1 year, was analysed using Cox proportional hazards regression. Secondary endpoints included major adverse cardiac events (MACE) (cardiovascular death, acute myocardial infarction, life-threatening arrhythmia and acute heart failure), analysed using Fine–Grey hazard regression. All models were adjusted for prespecified confounders with PMI as a time-varying exposure. Results: Amongst 4634 older patients (median age 80 years; 42.9% women), PMI occurred in 892 patients (19.2%), which was higher than in younger patients (P < .0001). The distribution of PMI aetiologies was comparable between groups. At 1 year, all-cause mortality was 26.2% in patients with PMI and 13.2% in patients without PMI, and MACE occurred in 30% versus 13%, respectively. After multivariable adjustment, the hazard ratio of PMI was highest on postoperative day 1 (all-cause mortality: 10.5 [95% CI 4.5–24.5]; MACE: 4.4 [95% CI 3.2–5.9]), declined by day 90 (1.4 [95% CI 1.0–1.9] and 2.2 [95% CI 1.7–2.7], respectively), and persisted through 1 year. Conclusions: PMI was very common amongst older patients and associated with substantially higher 1-year risks of all-cause mortality and MACE, with greatest vulnerability observed during the initial 90 postoperative days.

Cancer is associated with biological aging and functional decline; however, few studies have simultaneously examined objective changes in physical function and biological aging in older adults who develop cancer. We therefore compared functional and accelerated aging in generally healthy adults with and without incident invasive cancer, using data from DO-HEALTH, a three-year, randomized controlled trial including 2152 participants (mean age: 74.9 years, 61.1% women), free of major health conditions. Functional aging was assessed by the Short Physical Performance Battery, handgrip strength, gait speed, and five-times sit-to-stand test (STS). Biological aging was measured in a subsample ( n = 777) using Horvath, Hannum, GrimAge and PhenoAge clocks, and DunedinPACE. Participants with incident cancer showed a greater decline in STS (Δ adjusted means [AM]: 0.64 s [95% CI 0.06, 1.22]) and grip strength (ΔAM −1.77 kPa [−3.51, −0.03]). Furthermore, baseline biological aging was accelerated between 3.52 and 6.77 months, measured by Horvath, Hannum, and PhenoAge clocks. Findings support the geroscience hypothesis linking greater phenotypic functional decline to accelerated biological aging in older adults with incident cancer. The data for this observational analysis stem from the DO-HEALTH clinical trial, which was prospectively registered (clinicaltrials.gov; NCT01745263; registered on December 10, 2012).

Background: The ICEBERG tool was initially validated in two small pilot studies to address the lack of a comprehensive geriatric screening tool in emergency settings. The present study builds on the second pilot study and extends it to a larger, multicenter sample. Methods: We report results from a large ICEBERG tool validation study across three emergency rooms (ERs) including 1664 patients aged 70 years and older. The tool targets 9 domains and is administered by ER physicians or specialized nurses. To assess criterion validity—the extent to which ICEBERG scores are associated with relevant clinical outcomes—we compared patients who scored below versus above the median (<10; ≥10) ICEBERG score for six key clinical outcomes: length of stay in acute care, nursing care in minutes, one-on-one nursing care, in-hospital mortality, discharge to nursing home, and readmission within 30 days. Negative binomial regression was used for the outcomes length of stay and nursing care in minutes. Logistic regression was used for the other outcomes. All analyses were adjusted for age and sex. Results: Patients with ICEBERG scores of 10 or higher had significantly longer stays in acute care (8.9 vs 6.6 days), required more nursing care (56.4 vs 32.8 h), had higher odds of one-on-one nursing care (Odds Ratio, OR = 2.85), in-hospital mortality (OR = 1.89), discharge to a nursing home (OR = 3.20), or being readmitted within 30 days (OR = 1.81). Conclusions: Based on our findings, the ICEBERG tool identifies older patients with a geriatric risk profile at ERs on all key clinical outcomes tested.

Background: Recent meta-analyses of randomized controlled trials (RCTs) have raised concerns that treatment with omega-3 fatty acids may increase risk of atrial fibrillation (AF). However, these meta-analyses included at most eight trials. The aim of this current meta-analysis was to expand the search by including other eligible omega-3 RCTs with AF incidence data, incorporating both published and unpublished data. Methods: Eligible studies were RCTs investigating daily doses of ≥500 mg/d of docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA). Additional inclusion criteria included ≥12 months treatment with EPA/DHA, participants ≥ 50 years of age, and where possible, the absence of known AF/atrial flutter at baseline. The primary outcome was occurrence of new-onset AF. Our primary hypothesis was that risk for AF would simultaneously depend on both omega-3 dose (above or below 1500 mg/d) and background cardiovascular disease (CVD) risk status, and that their combined impact on AF risk would be synergistic. Results: A total of 34 RCTs (36 datasets; n=114,326) were included in this meta-analysis. Only studies including patients at high-risk for CVD who were treated with high-doses of EPA/DHA (>1500 mg/day) showed a statistically significant increase in AF risk with a pooled odds ratio (OR) of 1.48 (95% CI, 1.21-1.81) and an absolute risk difference of 0.8% (0.40-1.1%). None of the other three groups showed statistically significant levels of AF risk (ORs 1.07 (high risk, low dose), 1.06 (low risk, low dose) and 0.95 (low risk, high dose). Conclusion: This meta-analysis suggests that treatment with EPA/DHA is most likely to increase risk for AF in patients at high-risk for CVD who are treated with high doses of EPA/DHA. The risk for AF should be balanced against the benefits of EPA/DHA in making treatment decisions.

Proton-pump inhibitors (PPI) are widely used among older adults and PPI intake has been associated with increased fracture risk. However, their association with bone microarchitecture and strength remains unclear as prior clinical PPI studies were restricted to lower-resolution bone imaging techniques such as DXA. Using high-resolution peripheral computed tomography (HR-pQCT), we prospectively investigated whether long-term PPI use was associated with changes in volumetric bone mineral densities, bone microarchitecture, and strength in older patients. 189 patients aged ≥ 60 years ( n = 24 persistent PPI users [p-PPI user], and n = 165 non-PPI users), enrolled as part of a 2-year vitamin D RCT, underwent HR-pQCT scanning of the tibia and radius at 0 and 2 years. Bone volumetric density (vBMD), microarchitectural and strength parameters were computed and adjusted linear regression models without and with adjustments, including age, sex, BMI, and treatment groups, were employed to compare changes between p-PPI users and non-PPI users. At baseline, both groups were comparable with respect to age, vBMDs, bone microarchitecture, and sex. During follow-up, p-PPI users lost significantly more distal tibial total volumetric BMD (ΔTt.BMD: − 8.58 vs. − 2.45 mg/cm ³ , p = 0.012) and cortical volumetric BMD (ΔCt.BMD, − 28.96 vs. -14.07 mg/cm ³ , p = 0.005), and showed a significantly greater loss in tibial bone strength (Δstiffness − 4848.1 vs. 20.7 N/mm, p = 0.029; Δfailure load − 204.5 vs. 16.7 N, p = 0.026) than non-PPI users. At the radius, p-PPI users showed over the 2 years significantly greater increases in cortical porosity and intracortical pore diameter than non-PPI users (ΔCt.Po, p = 0.005; ΔCt.PoDm, p = 0.009). Long-term PPI intake was associated with a significant decline in cortical microarchitecture at the radius and with a significant deterioration of volumetric bone mineral density and strength at the tibia in older patients.

While frailty and anemia are prevalent conditions in aging linked to adverse outcomes, their relationship remains understudied in generally healthy older adults. We conducted a post-hoc observational study among all participants of DO-HEALTH, the largest European clinical trial designed to support healthy aging. Our analysis examined whether baseline hemoglobin levels and anemia are associated with being at least pre-frail at baseline and any yearly follow-up time point over three years. Frailty status was assessed by the Fried frailty phenotype at baseline and at each annual follow-up visit. Participants were considered at least pre-frail by the presence of any frailty domain (fatigue, unintentional weight loss, slowness, weakness, low activity). For both hemoglobin levels and anemia as predictors, we used regression models based on generalized estimating equations controlling for potential confounders. In total, 2,123 of 2,157 participants had available frailty status and hemoglobin levels at baseline and were included in the analysis (mean age 74.9 years; 61.7% women). At baseline, 46.4% ( n = 986) were at least pre-frail, while the mean hemoglobin level was 139.7 g/L (SD 12.5), and 6.7% ( n = 141) had anemia. In our multivariate prospective analysis, each 10-g/L decrease in baseline hemoglobin levels was associated with 8% higher odds of pre-frailty (adjusted Odds Ratio [aOR] 1.08, 95%CI 1.01–1.16, p 0.02), and baseline anemia was associated with 39% higher odds of pre-frailty over three years (aOR = 1.39, 95%CI 1.02–1.88, p 0.03). In conclusion, our results provide novel insights into the association between hemoglobin levels, anemia, and pre-frailty in generally healthy and active older adults.