C1q-binding ability may indicate the clinical relevance of de novo donor-specific anti-HLA antibodies (DSA). This study investigated the incidence and risk factors for the appearance of C1q-binding de novo DSA and their long-term impact. Using Luminex Single Antigen Flow Bead assays, 346 pretransplant nonsensitized kidney recipients were screened at 2 and 5 years after transplantation for de novo DSA, which was followed when positive by a C1q Luminex assay. At 2 and 5 years, 12 (3.5%) and eight (2.5%) patients, respectively, had C1q-binding de novo DSA. De novo DSA mean fluorescence intensity .6237 and .10,000 at 2 and 5 years, respectively, predicted C1q binding. HLA mismatches and cyclosporine A were independently associated with increased risk of C1q-binding de novo DSA. When de novo DSA were analyzed at 2 years, the 5-year death-censored graft survival was similar between patients with C1q-nonbinding de novo DSA and those without de novo DSA, but was lower for patients with C1q-binding de novo DSA (P=0.003). When de novo DSA were analyzed at 2 and 5 years, the 10-year death-censored graft survival was lower for patients with C1q-nonbinding de novo DSA detected at both 2 and 5 years (P,0.001) and for patients with C1q-binding de novo DSA (P=0.002) than for patients without de novo DSA. These results were partially confirmed in two validation cohorts. In conclusion, C1q-binding de novo DSA are associated with graft loss occurring quickly after their appearance. However, the long-term persistence of C1q-nonbinding de novo DSA could lead to lower graft survival.

The Geroscience aims at a better understanding of the biological processes of aging, to prevent and/or delay the onset of chronic diseases and disability as well as to reduce the severity of these adverse clinical outcomes. Geroscience thus open up new perspectives of care to live a healthy aging, that is to say without dependency. To date, life expectancy in healthy aging is not increasing as fast as lifespan. The identification of biomarkers of aging is critical to predict adverse outcomes during aging, to implement interventions to reduce them, and to monitor the response to these interventions. In this narrative review, we gathered information about biomarkers of aging under the perspective of Geroscience. Based on the current literature, for each hallmark of biological aging, we proposed a putative biomarker of healthy aging, chosen for their association with mortality, age-related chronic diseases, frailty and/or functional loss. We also discussed how they could be validated as useful predictive biomarkers.

E. Forestier). y Forestier Emmanuel and Claire Roubaud-Baudron are joint first authors.x The members of the collab group AEPEI and the GInGer Elderl-IE study group are listed under the Acknowledgements section. Contents lists available at ScienceDirect Clinical Microbiology and Infectionj o u r n a l h o m e p a g e : w w w . c l i n i c a l m i c r o b i o l o g y a n d i n f e c t i o n . c o m

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OBJECTIVES To assess the associations of long‐term lifestyle multidomain intervention (MI) and omega‐3 supplementation with frailty level evolution and frailty incidence in community‐dwelling older persons. DESIGN Secondary analysis of the randomized controlled Multidomain Alzheimer Preventive Trial. SETTING Thirteen memory centers in France and Monaco between 2008 and 2011. PARTICIPANTS A total of 1588 community‐dwelling persons aged 70 years or older with memory complaints (without dementia), slow gait speed, or limitation in one instrumental activity of daily living. INTERVENTION A 3‐year MI (43 group sessions including cognitive training, physical activity, and nutrition advice and three preventive consultations) plus daily omega‐3 fatty acids, MI plus placebo, omega‐3 alone, or placebo alone. MEASUREMENTS The frailty phenotype (unintentional weight loss, exhaustion, low physical activity, slow gait, low handgrip strength: 0 to 5 score, higher is worse; a score of 3 or higher defines frailty) was assessed at baseline, 6, 12, 24, and 36 months. We used mixed‐effect models for frailty level (0‐5 score as an ordinal variable) and Cox models for frailty incidence. RESULTS No differences were found between the intervention groups and placebo on the 3‐year evolution of frailty level. Among 1394 non‐frail participants at baseline, frailty incidence occurred in 134 (9.6%) persons: 26 (7.6%) in the MI plus omega‐3 group, 34 (10%) in the omega‐3 alone group, 31 (8.5%) in the MI plus placebo group, and 43 (12.3%) in the placebo‐alone group). No differences regarding frailty incidence were found between intervention groups and placebo. After exclusion of 53 participants with incident frailty during the first year of follow‐up, MI plus omega‐3 was associated with a lower frailty incidence compared with placebo (hazard ratio = .43; 95% confidence interval = .22‐.81). CONCLUSION In community‐dwelling older persons, the combination of a long‐term lifestyle MI and omega‐3 supplementation did not reduce frailty level or incidence. The reduction of frailty incidence associated with the combined intervention in a sensitivity analysis needs to be further confirmed. J Am Geriatr Soc 67:1700–1706, 2019

Background and objectivesLow eGFR is known to be associated with frailty, but the association between the longitudinal decline of eGFR and incident frailty in older persons remains to be determined. The objective of this study was to investigate whether a fast decline on eGFR would be associated with incident frailty.Design, setting, participants, & measurementsCommunity dwellers, aged ≥70, were included in this secondary analysis of the 5-year Multidomain Alzheimer Preventive Trial (MAPT). eGFR was calculated using CKD–Epidemiology Collaboration equation at baseline and at 6, 12, and 24 months. The lowest quartile of eGFR slope (−4.1 ml/min per 1.73 m2 per yr) defined a fast decline. The frailty phenotype (unintentional weight loss, exhaustion, low physical activity, slow gait, low handgrip strength assessed with a 0–5 score, where higher is worse; a score ≥3 defines frailty) was assessed at baseline, 6, 12, 24, 36, 48, and 60 months. Cox models were used to test the association between fast eGFR decline and incident frailty.ResultsA total of 833 participants were frail neither at baseline nor at 2 years and had appropriate follow-up data. Median (IQR) baseline eGFR was 73 (61–84) ml/min per 1.73 m2. Frailty occurred in 95 (11%) participants between 24 and 60 months. Among them, 31/207 (15%) had fast eGFR decline between baseline and 24 months, and 64/626 (10%) did not. In a Cox model adjusted for demographic variables, cardiovascular comorbidity, C-reactive protein, and baseline eGFR, a fast eGFR decline was associated with incident frailty (HR 1.67, 95% CI 1.03 to 2.71). Sensitivity analyses provided consistent findings.ConclusionsIn community-dwelling older adults with relatively preserved baseline eGFR, a fast eGFR decline is associated with incident frailty.