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Inflammaging, a state of chronic, progressive low-grade inflammation during aging, is associated with several adverse clinical outcomes, including frailty, disability, and death. Chronic inflammation is a hallmark of aging and is linked to the pathogenesis of many aging-related diseases. Anti-inflammatory therapies are also increasingly being studied as potential anti-aging treatments, and clinical trials have shown benefits in selected aging-related diseases. Despite promising advances, significant gaps remain in defining, measuring, treating, and integrating inflammaging into clinical geroscience research. The Clin-STAR Inflammation Research Interest Group was formed by a group of transdisciplinary clinician-scientists with the goal of advancing inflammaging-related clinical research and improving patient-centered care for older adults. Here, we integrate insights from nine medical subspecialties to illustrate the widespread impact of inflammaging on diseases linked to aging, highlighting the extensive opportunities for targeted interventions. We then propose a transdisciplinary approach to enhance understanding and treatment of inflammaging that aims to improve comprehensive care for our aging patients., (© 2024. The Author(s), under exclusive licence to American Aging Association.)

Chronological age is not an accurate predictor of morbidity and mortality risk, as individuals' aging processes are diverse. Phenotypic age acceleration (PhenoAgeAccel) is a validated biological age measure incorporating chronological age and biomarkers from blood samples commonly used in clinical practice that can better reflect aging-related morbidity and mortality risk. The heterogeneity of age-related decline is not random, as environmental exposures can promote or impede healthy aging. Social Vulnerability Index (SVI) is a composite index accounting for different facets of the social, economic, and demographic environment grouped into four themes: socioeconomic status, household composition and disability, minority status and language, and housing and transportation. We aim to assess the concurrent and combined associations of the four SVI themes on PhenoAgeAccel and the differential effects on disadvantaged groups. We use electronic health records data from 31,913 patients from the Mount Sinai Health System (116,952 person-years) and calculate PhenoAge for years with available laboratory results (2011-2022). PhenoAge is calculated as a weighted linear combination of lab results and PhenoAgeAccel is the differential between PhenoAge and chronological age. A decile increase in the mixture of SVI dimensions was associated with an increase of 0.23 years (95% CI: 0.21, 0.25) in PhenoAgeAccel. The socioeconomic status dimension was the main driver of the association, accounting for 61% of the weight. Interaction models revealed a more substantial detrimental association for women and racial and ethnic minorities with differences in leading SVI themes. These findings suggest that neighborhood-level social vulnerability increases the biological age of its residents, increasing morbidity and mortality risks. Socioeconomic status has the larger detrimental role amongst the different facets of social environment.

Background: There is a lack of real-life data regarding the frequency and predictive factors of hypoglycemia in older patients with type 2 diabetes (T2D). This study aimed to determine the frequency and predictors of hypoglycemia in older patients with insulin-treated T2D., Methods: This prospective multicenter study included 155 insulin-treated T2D patients aged 75 years and older with ≥2 self-monitoring of blood glucose (SMBG) daily controls. Participants underwent a geriatric and diabetic assessment and received ambulatory blinded continuous glucose monitoring (CGM) for 28 consecutive days with FreeStyle Libre Pro® sensor. Study population (n = 141) has >70% CGM active time. Multivariable logistic regressions were used to identify factors associated with SMBG confirmed hypoglycemia (≥70 mg/dL) and with nocturnal level 2 time below range (glucose concentration <54 mg/dL during ≥15 consecutive min between 0.00 and 6.00 am)., Results: The mean age of the 141 analyzed patients was 81.5 ± 5.3 years and 56.7% were male. The mean baseline HbA 1c was 7.9% ± 1.0%. After geriatric assessment, 102 participants (72.3%) were considered as complex and 39 (27.7%) as healthy. The primary endpoint (confirmed SMBG <70 mg/dL) occurred in 37.6% patients. In multivariable analysis, the risk of SMBG-confirmed hypoglycemia was positively associated with a longer duration of diabetes (OR (+1 year) =1.04, (1.00-1.08), p = 0.04) and glycemic variability assessed by CGM (CV %) (OR (+1%) = 1.12, [1.05-1.19], p = <0.001). Nighty-two patients (65.2%) experienced nocturnal time in hypoglycemia (i.e., <54 mg/dL during ≥15 consecutive min between midnight and 6 a.m.). In multivariable analyses, cognitive impairment (OR: 9.31 [2.59-33.4]), heart failure (OR: 4.81 [1;48-15.6]), and depressive disorder (OR: 0.19 [0.06-0.53]) were associated with nocturnal time in hypoglycemia., Conclusion: Nocturnal hypoglycemia is very common and largely underdiagnosed in older patients with insulin-treated T2D. CGM is a promising tool to better identify hypoglycemia and adapt diabetes management in this population., (© 2023 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Since the development of antibiotics and vaccination, as well as major improvements in public hygiene, the main risk factors for morbidity and mortality are age and chronic exposure to environmental factors, both of which can interact with genetic predispositions. As the average age of the population increases, the prevalence and costs of chronic diseases, especially neurological conditions, are rapidly increasing. The deleterious effects of age and environmental risk factors, develop chronically over relatively long periods of time, in contrast to the relatively rapid deleterious effects of infectious diseases or accidents. Of particular interest is the hypothesis that the deleterious effects of environmental factors may be mediated by acceleration of biological age. This hypothesis is supported by evidence that dietary restriction, which universally delays age-related diseases, also ameliorates deleterious effects of environmental factors. Conversely, both age and environmental risk factors are associated with the accumulation of somatic mutations in mitotic cells and epigenetic modifications that are a measure of "biological age", a better predictor of age-related morbidity and mortality than chronological age. Here we review evidence that environmental risk factors such as smoking and air pollution may also drive neurological conditions, including Alzheimer's Disease, by the acceleration of biological age, mediated by cumulative and persistent epigenetic effects as well as somatic mutations. Elucidation of such mechanisms could plausibly allow the development of interventions which delay deleterious effects of both aging and environmental risk factors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Knobel, Litke and Mobbs.)

Discovery of interventions that delay or minimize age-related diseases is arguably the major goal of aging research. Conversely discovery of interventions based on phenotypic screens have often led to further elucidation of pathophysiological mechanisms. Although most hypotheses to explain lifespan focus on cell-autonomous processes, increasing evidence suggests that in multicellular organisms, neurons, particularly nutrient-sensing neurons, play a determinative role in lifespan and age-related diseases. For example, protective effects of dietary restriction and inactivation of insulin-like signaling increase lifespan and delay age-related diseases dependent on Creb-binding protein in GABA neurons, and Nrf2/Skn1 in just 2 nutrient-sensing neurons in C. elegans. Screens for drugs that increase lifespan also indicate that such drugs are predominantly active through neuronal signaling. Our own screens also indicate that neuroactive drugs also delay pathology in an animal model of Alzheimer's Disease, as well as inhibit cytokine production implicated in driving many age-related diseases. The most likely mechanism by which nutrient-sensing neurons influence lifespan and the onset of age-related diseases is by regulating metabolic architecture, particularly the relative rate of glycolysis vs. alternative metabolic pathways such as ketone and lipid metabolism. These results suggest that neuroactive compounds are a most promising class of drugs to delay or minimize age-related diseases., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Osteoporosis in older men is common and causes significant mortality and morbidity. Some data suggest that conditions leading to bone fragility, including osteoporosis, are under-identified and undertreated in men. Additionally, 50% of the causes of osteoporosis are secondary in men. The latest Endocrine Society and different Rheumatology Societies Guidelines recommend additional laboratory investigations in men with osteoporosis so as to treat them more efficiently., Main Goal of the Study: Our aim was to determine whether men managed in our geriatrics center, diagnosed with osteoporosis, underwent investigations to determine the aetiology of osteoporosis and other bone fragility conditions and what the secondary causes were., Materials and Method: We conducted a monocentric, retrospective study including all men seen at the geriatric consult in 2016 diagnosed with osteoporosis. For each patient, we evaluated our clinical practice, whether common secondary causes were sought-after and what these aetiologies were., Results: Among the 121 men with a diagnosis of osteoporosis seen at the geriatric consult at the Lille University Hospital in 2016, only 51 had undergone further investigations. Among the 3 major secondary causes were identified: 17.6% glucocorticoid induced, 13.7% treatment induced hypogonadism, 11.7% late onset hypogonadism., Conclusions: A more efficient etiological assessment of osteoporosis in older men could be achieved and would improve management for our patients. This can be achieved by a better knowledge of the recommendations for etiological assessment of bone fragility and osteoporosis and a dedicated consultation within the geriatric sector., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

The impact of dietary advanced glycation end products (dAGEs) on human health has been discussed in many studies but, to date, no consensual pathophysiological process has been demonstrated. The intestinal absorption pathways which have so far been described for dAGEs, the passive diffusion of free AGE adducts and transport of glycated di-tripeptides by the peptide transporter 1 (PEPT-1), are not compatible with certain pathophysiological processes described. To get new insight into the intestinal absorption pathways and the pathophysiological mechanisms of dAGEs, we initiated an in vivo study with a so-called simple animal model with a complete digestive tract, Caenorhabditis elegans . Dietary bacteria were chemically modified with glyoxylic acid to mainly produce Nε -carboxymethyllysine (CML) and used to feed the worms. We performed different immunotechniques using an anti-CML antibody for the relative quantification of ingested CML and localization of this AGE in the worms' intestine. The relative expression of genes encoding different biological processes such as response to stresses and intestinal digestion were determined. The physiological development of the worms was verified. All the results were compared with those obtained with the control bacteria. The results revealed a new route for the intestinal absorption of dietary CML (dCML), endocytosis, which could be mediated by scavenger receptors. The exposure of worms to dCML induced a reproductive defect and a transcriptional response reflecting oxidative, carbonyl and protein folding stresses. These data, in particular the demonstration of endocytosis of dCML by enterocytes, open up new perspectives to better characterize the pathophysiological mechanisms of dAGEs.

Purpose: Although Alzheimer disease and related dementias (ADRDs) have long been considered nonpreventable and even an inevitable consequence of aging, recent findings from longitudinal studies indicate a downtrend in age-adjusted incidence and prevalence of ADRDs in Western countries. This remarkable trend might be the result of improved management of so-called modifiable risk factors. The aim of this review is to present evidence of modifiable factors of ADRDs in a life-course approach., Methods: A PubMed database search was conducted between November and December 2020 to identify relevant studies evaluating the role of modifiable risk factors in the development of ADRDs. Key words (Alzheimer's disease and modifiable risk factors) were used and specific inclusion and exclusion criteria applied., Findings: This review identifies modifiable factors for ADRDs divided into early-life, middle-life, and late-life risk factors, depending on the available window of preventive action. According to life course exposure, factors can be protective or deleterious for ADRDs that participate in the underlying pathophysiologic complexity of these diseases as well as the complexity for public health measures implementations., Implications: The available evidence derived from epidemiologic, preclinical, interventional studies suggest that modifiable risk factors for ADRDs offer opportunities for therapeutic and preventive actions., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aging is a physiological and complex process associated with increasing age of living organisms. Simple model organisms have brought significant advances in our understanding of the aging process. Caenorhabditis elegans, a nematode originally used to establish the genetic and molecular basis of development, has become one of the leading model organisms for research on aging. This invertebrate has allowed identifying a connection between cellular signaling pathways and longevity. Although C. elegans is not suitable for analysis of the complete process of human aging, it remains a model of choice to analyze specific aging mechanisms and phenotypes., (© 2018 médecine/sciences – Inserm.)

Advanced glycation end-product (AGE) is the generic term for a heterogeneous group of derivatives arising from a non-enzymatic reaction between reducing sugars and proteins. In recent years, evidence has accumulated that incriminates AGEs in pathogenic processes associated with both chronic hyperglycaemia and age-related diseases. Regardless of their exogenous or endogenous origin, the accumulation of AGEs and their derivatives could promote accelerated ageing by leading to protein modifications and activating several inflammatory signalling pathways via AGE-specific receptors. However, it remains to be demonstrated whether preventing the accumulation of AGEs and their effects is an important therapeutic option for successful ageing. The present review gives an overview of the current knowledge on the pathogenic role of AGEs by focusing on three AGE target organs: kidney, heart and brain. For each of these organs we concentrate on an age-related disease, each of which is a major public health issue: chronic kidney disease, heart dysfunction and neurodegenerative diseases. Even though strong connections have been highlighted between glycation and age-related pathogenesis, causal links still need to be validated. In each case, we report evidence and uncertainties suggested by animal or epidemiological studies on the possible link between pathogenesis and glycation in a chronic hyperglycaemic state, in the absence of diabetes, and with exogenous AGEs alone. Finally, we present some promising anti-AGE strategies that are currently being studied., (© 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.)

Whether the glycaemic control during the first hours of cerebral ischaemia treated by thrombolysis influences outcomes remains unsettled. We aimed at evaluating the quality of the glycaemic control and whether patients with well-controlled glycaemia after thrombolysis for acute cerebral ischaemia have better outcomes. We retrospectively analysed data prospectively collected in consecutive stroke patients who received i.v. thrombolysis at the Lille University Hospital. Patients with glycaemia >1.6 g/l (8.9 mmol/l) at any point during the first 48 h received insulin. We used 2 definitions of well controlled glycaemia: (i) "well controlled 100 %" when 100 % glycaemia were <1.6 g/l (8.9 mmol/l), and (ii) "well controlled 70 %" when at least 70 % glycaemia were <1.6 g/l (8.9 mmol/l). The outcome measures at 3 months were (1) independence [modified Rankin scale (mRS) score 0 or 1], (2) absence of handicap (mRS 0-2), (3) death, and (4) symptomatic intracerebral haemorrhage (sICH). Of 875 consecutive patients, 657 (75.2 %) were considered as well controlled with a threshold at 100 % and 736 (84.2 %) with a threshold at 70 %. The glycaemic control was not independently associated with any of the four outcome measures. In patients treated by insulin, hypoglycaemic events were rare (2.1 % of all patients) and of moderate intensity [>0.5 g/l (2.8 mmol/l)]. The quality of the glycaemic control was not associated with outcomes in patients treated by thrombolysis. A possible explanation is that the glycaemic control after thrombolysis has minor influence compared with glycaemic control before thrombolysis when the artery is not yet re-open and the penumbra area at maximum.