Age-related Diseases Research Articles

Association of low muscle mass index and sarcopenic obesity with knee osteoarthritis: a systematic review and meta-analysis.

Sarcopenia and knee osteoarthritis are common age-related diseases that have become important public health issues worldwide. Few studies have reported the association between muscle mass loss and knee osteoarthritis. This may be due to the high level of heterogeneity between studies stemming from different definitions of muscle mass loss. The systematic searches were carried out in PubMed and Web of Science from the inception of the databases until 13 January 2023, by two independent researchers. Pooled odds ratios (ORs) for overall and subgroup analyses were obtained using either a random effects model (I2 >50%) or fixed effects model (I2 ≤50%) in Stata. Of the 1,606 studies identified, we ultimately included 12 articles on the association between muscle mass and knee osteoarthritis (prospective: n = 5; cross-sectional: n = 7). Low-quality evidence indicated that low muscle mass index and sarcopenic obesity increase the odds of knee osteoarthritis (low muscle mass index OR: 1.36, 95% CI: 1.13-1.64; sarcopenic obesity OR: 1.78, 95% CI: 1.35-2.34). However, no association was observed between general sarcopenia or low muscle mass with knee osteoarthritis. This systematic review and meta-analysis revealed that low muscle mass index and sarcopenic obesity were associated with an increased risk of developing knee osteoarthritis.

Health-Related Behaviors and Risk of Common Age-Related Brain Diseases Across Severities of Genetic Risk.

The 21-point Brain Care Score (BCS) is an index that ranks behaviors and clinical measurements with the aim of encouraging lifestyle adjustments to lower the incidence of age-related brain disease, including stroke, late-life depression (LLD), and dementia. A higher BCS at baseline is associated with a lower risk of these outcomes. We aimed to investigate whether the associations between BCS and stroke, LLD, and dementia risks are independent of genetic predisposition for these conditions and quantify the effect of healthy lifestyle across genetic risk distributions for these outcomes. Using the UK Biobank (UKB) prospective cohort study, we computed baseline BCSs and polygenic scores to estimate genetic predisposition for stroke and LLD and APOE ε allele status to stratify dementia risk. As for outcomes again in UKB, we measured incidence of stroke, LLD, and dementia. We used multivariate Cox proportional hazard models to assess associations between BCS, genetic predisposition, and these outcomes. We also conducted stratified and interaction analyses to estimate the incidence of these outcomes across quartiles of genetic risk and BCS. We included 368,340 UKB participants (median age 58 years (interquartile range 51-63 years), 46.3% male). Independent of genetic risk, a 5-point increase in BCS corresponded to lowered hazards of stroke (hazard ratio [HR] 0.70, 95% CI 0.68-0.73), LLD (HR 0.65, 95% CI 0.63-0.67), and dementia (HR 0.82, 95% CI 0.78-0.85). Incidences of all 3 outcomes were higher among participants with high genetic risk of these outcomes. However, these increased risks were offset for individuals with a higher BCS (incidence rates per 1,000 person-years were 2.76 vs 1.19 for stroke, 7.34 vs 4.46 for LLD, and 3.64 vs 2.05 for dementia, when comparing low and high BCS). Across different genetic predispositions for stroke, LLD, and dementia, healthier lifestyle behaviors are protective for brain health, demonstrating the nondeterminism of genetic risk. Furthermore, differences in BCS behave as aggregate risk estimators of all 3 outcomes. Further work is needed to prospectively investigate the utility and performance of the BCS as a targeted intervention in populations at elevated genetic risk of age-related brain disease.

Efficacy of intravitreal faricimab therapy for polypoidal choroidal vasculopathy: A systematic review and meta-analysis.

Polypoidal choroidal vasculopathy (PCV) is an aneurismal type of macular neovascularization that show similarities with age-related macular degeneration and diseases that are part of the pachychoroid disease spectrum. Exudative changes in PCV can be treated with intravitreal anti-vascular endothelial growth factor monotherapy; however, a combination therapy with photodynamic therapy may be required. In this systematic review and meta-analysis, we evaluated the efficacy of faricimab for PCV. We searched 12 literature databases for eligible studies. All study evaluation and data extraction were made by two authors in duplicate. Studies eligible for analysis were included for a qualitative and quantitative review. We identified seven studies with data from 150 eyes with PCV, five studies were of treatment-naïve eyes who were commenced in faricimab monotherapy, and two studies were of switch-over to faricimab from other anti-VEGF drugs. After faricimab loading dose in treatment-naïve eyes, the best-corrected visual acuity (BCVA) remained stable at -0.09 (95% CI: -0.20-0.03) logMAR, central retinal thickness (CRT) decreased -169 (95% CI: -311--27) μm, and 48.7 (95% CI: 32.5-65.0) % of eyes obtained polyp closure. In switch-over eyes, 57%-67% experienced fluid reduction and 21% were able to extend their treatment interval. In conclusion, faricimab monotherapy for PCV leads to acceptable clinical outcomes in terms of stable BCVA, reduction of CRT, and high incidence of polyp closure. Some cases may benefit from a switch to faricimab. However, long-term efficacy studies and controlled comparative studies are warranted.

Senescence as a therapeutic target in cancer and age-related diseases.

Cellular senescence is a stress response that restrains the growth of aged, damaged or abnormal cells. Thus, senescence has a crucial role in development, tissue maintenance and cancer prevention. However, lingering senescent cells fuel chronic inflammation through the acquisition of a senescence-associated secretory phenotype (SASP), which contributes to cancer and age-related tissue dysfunction. Recent progress in understanding senescence has spurred interest in the development of approaches to target senescent cells, known as senotherapies. In this Review, we evaluate the status of various types of senotherapies, including senolytics that eliminate senescent cells, senomorphics that suppress the SASP, interventions that mitigate senescence and strategies that harness the immune system to clear senescent cells. We also summarize how these approaches can be combined with cancer therapies, and we discuss the challenges and opportunities in moving senotherapies into clinical practice. Such therapies have the potential to address root causes of age-related diseases and thus open new avenues for preventive therapies and treating multimorbidities.

Linguistic Markers of Subtle Cognitive Impairment in Connected Speech: A Systematic Review.

This systematic review covers the current stage of research on subtle cognitive impairment with connected speech. It aims at surveying the linguistic features in use to single out those that can best identify patients with mild neurocognitive disorders (mNCDs), whose cognitive changes remain underdiagnosed. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and proposed a full definition of features for the analysis of speech features. Fifty-one studies met the inclusion criteria. Most of them focused on age-related progressive diseases and included fewer than 30 subjects. A total of 384 features labeled with 335 different names was retrieved, yielding various results in discriminating individuals with mNCDs from controls. This finding highlights the need for harmonized labels to further investigate mNCDs with linguistic markers. We suggest two different ways of assessing a feature's reliability. We also point out potential methodological issues that remain to be resolved, along with recommendations for reproducible research in the field.

Psychotropic-induced weight gain and telomere length: results from a one-year longitudinal study and a large population-based cohort.

Weight-inducing psychotropic treatments are risk factors for age-related diseases such as cardiovascular disorders, which are associated with both inflammation and telomere length shortening. With a longitudinal design, the present study evaluates telomere length trajectories after 1 year of weight-inducing psychotropic medication, accounting for weight changes and the inflammatory biomarker high-sensitivity C-Reactive Protein (CRP). Among 200 patients, an overall median telomere shortening of -41.2 bp was observed (p = 0.014), which is comparable with the general population's yearly telomere attrition. Linear regression showed on average -93.1 and -58.9 bp of further telomere shortening per five units of BMI for BMI values < or ≥30 kg/m2, respectively (p = 0.003 and p = 0.009, respectively). Importantly, the overall telomere shortening was predicted to be increased four-fold among patients with low baseline weight (i.e., 50 kg) and with clinically relevant weight gain (≥ 7%) after 1 year of treatment (interaction term between relevant weight gain and baseline weight: +6.3 bp, p = 0.016). Patients with relevant weight gain showed greater CRP levels (+ 49%; p = 0.016), and a telomere shortening of -36.2 bp (p = 0.010) was estimated whenever CRP level doubled. Mendelian randomization using UKBiobank data showed a causal effect of BMI on telomere shortening, notably stronger among patients receiving weight-inducing psychotropic treatments (n = 9798) than among psychiatric patients without such drugs (n = 16228) and non-psychiatric controls (n = 252932) (beta: -0.37, -0.12, -0.06, respectively; p = 0.004, p < 0.001, p < 0.001, respectively). Ultimately, telomere trajectories were associated with 1 year weight gain and increases in CRP levels, with telomere shortening strongly enhanced by BMI increments among patients receiving weight-inducing psychotropic treatments.

Reactivation of senescence-associated endogenous retroviruses by ATF3 drives interferon signaling in aging.

Reactivation of endogenous retroviruses (ERVs) has been proposed to be involved in aging. However, the mechanism of reactivation and contribution to aging and age-associated diseases is largely unexplored. In this study, we identified a subclass of ERVs reactivated in senescent cells (termed senescence-associated ERVs (SA-ERVs)). These SA-ERVs can be bidirectional transcriptionally activated by activating transcription factor 3 (ATF3) to generate double-stranded RNAs (dsRNAs), which activate the RIG-I/MDA5-MAVS signaling pathway and trigger a type I interferon (IFN-I) response in senescent fibroblasts. Consistently, we found a concerted increased expression of ATF3 and SA-ERVs and enhanced IFN-I response in several tissues of healthy aged individuals and patients with Hutchinson-Gilford progeria syndrome. Moreover, we observed an accumulation of dsRNAs derived from SA-ERVs and higher levels of IFNβ in blood of aged individuals. Together, these results reveal a previously unknown mechanism for reactivation of SA-ERVs by ATF3 and illustrate SA-ERVs as an important component and hallmark of aging.

Brain-wide alterations revealed by spatial transcriptomics and proteomics in COVID-19 infection.

Understanding the pathophysiology of neurological symptoms observed after severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection is essential to optimizing outcomes and therapeutics. To date, small sample sizes and narrow molecular profiling have limited the generalizability of findings. In this study, we profiled multiple cortical and subcortical regions in postmortem brains of patients with coronavirus disease 2019 (COVID-19) and controls with matched pulmonary pathology (total n = 42) using spatial transcriptomics, bulk gene expression and proteomics. We observed a multi-regional antiviral response without direct active SARS-CoV2 infection. We identified dysregulation of mitochondrial and synaptic pathways in deep-layer excitatory neurons and upregulation of neuroinflammation in glia, consistent across both mRNA and protein. Remarkably, these alterations overlapped substantially with changes in age-related neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. Our work, combining multiple experimental and analytical methods, demonstrates the brain-wide impact of severe acute/subacute COVID-19, involving both cortical and subcortical regions, shedding light on potential therapeutic targets within pathways typically associated with pathological aging and neurodegeneration.

Emerging roles of frailty and inflammaging in risk assessment of age-related chronic diseases in older adults: the intersection between aging biology and personalized medicine

Emerging roles of frailty and inflammaging in risk assessment of age-related chronic diseases in older adults: the intersection between aging biology and personalized medicine

A Case of Disseminated Tuberculosis with Atypical Presentation In An Older Person

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. It is a significant health concern, with millions of new cases and deaths reported each year. Disseminated tuberculosis (dTB) is a serious condition which can affect various organs and tissues, leading to widespread symptoms and complications. The diagnosis of dTB can be challenging due to its atypical presentations. We present a case of dTB in a robust older person who presented with musculoskeletal pain, weight loss, and loss of appetite. Initially, he was treated for age-related spine disease, and pain management was provided. However, his subsequent visit raised suspicion of TB, prompting further work up. The diagnosis was revised to dTB, and anti-TB treatment was initiated. The near miss or delay in diagnosis and treatment may have played a role in dissemination of disease, increased frailty and reduction of function in this patient. Healthcare workers must maintain a high index of suspicion and remain vigilant for TB as starting early treatment will prevent dissemination in the patient, reduce risk to the public and improve outcomes.

Connexins and Aging-Associated Respiratory Disorders: The Role in Intercellular Communications

This article reviews the contemporary understanding of the functional role of connexins in intercellular communications, their involvement in maintaining cellular and tissue homeostasis, and in aging-associated respiratory disease pathogenesis. Connexins are discussed as potential therapeutic targets. The review particularly focuses on the involvement of gap junction connexins and hemichannels in the transfer of calcium ions, metabolite molecules, ATP, and mitochondria through the cell membrane. Various disorders in the regulation of intercellular communication can heavily contribute to the pathogenesis of multiple diseases, including respiratory system diseases. A deeper understanding of molecular mechanisms underlying the activities of various connexins in gap junction channels will enable the prospective development of therapeutic approaches by either inhibiting or stimulating the activities of a certain connexin, while considering its critical functions in intercellular communications on the whole.

The role of anti-aging approaches in managing hypogonadism in sedentary older males

IntroductionWith thirty percent of the world’s population not getting enough exercise, Worldwide, physical inactivity ranks as one of the most common causes of premature mortality. Rapid drops in physical activity, decreased mobility, and early morbidity are aging characteristics. As the population over 80 continues to rise, aging raises the danger of age-related illnesses and changes in hormone release.AimUnderstanding the aging process is useful in developing pharmacological therapies and identifying therapeutic targets for age-related testosterone deficiency. Therefore, this study’s purpose is to present a thorough evaluation of the effects of anti-aging strategies on testosterone levels in older, inactive men.MethodsA literature search was completed for clinical and preclinical studies published in English between 2014 and 2024 related to age, sedentary life, testosterone, and anti-aging strategies.ResultsA sedentary lifestyle and low testosterone are linked to a vicious cycle. A sedentary lifestyle lowers testosterone levels, which leads to depression, exhaustion, low energy, and weakened bone and muscle strength. These effects exacerbate the detrimental consequences of aging and physical inactivity. Anti-aging techniques can prevent and treat age-related diseases, including calorie restriction, a balanced diet, regular exercise, weight control, diabetes management, and quitting smoking. Regular exercise raises total testosterone, free testosterone, and muscle steroidogenesis. In older men, testosterone replacement treatment increases bone density, cholesterol, protein synthesis, strength, erectile function, sexual desire, and general cognitive performance. However, some studies suggest dehydroepiandrosterone supplementation may provide health improvements without negative effects, potentially reversing arterial aging and reducing cardiovascular disease risk.ConclusionThis article evaluates the prospects for anti-aging procedures to assist in reducing the adverse effects of aging and physical inactivity in men.

Palmitoyl-L-carnitine induces tau phosphorylation and mitochondrial dysfunction in neuronal cells.

Alzheimer's disease (AD) is characterized by cognitive decline and memory loss, involving mechanisms such as tau hyperphosphorylation and mitochondrial dysfunction. Increasing evidence suggests that age-related alterations in metabolite levels are crucial for the pathogenesis of AD. Here, we analyzed serum metabolites from mice of various ages (2, 4, 14, and 21 months old) using mass spectrometry. We identified palmitoyl-L-carnitine as a key metabolite with significantly increased levels in aged mice. In vitro experiments with SH-SY5Y neuronal cells demonstrated that palmitoyl-L-carnitine treatment enhanced tau phosphorylation, increased mitochondrial fission, and elevated intracellular calcium levels. Furthermore, the increased levels of tau phosphorylation were significantly reduced by the inhibition of GSK-3β, CDK5, and calpain, indicating that tau kinases activated by calcium overload are directly involved in the increase of tau phosphorylation. Considering that mitochondrial fission is related to mitochondrial dysfunction, we propose that the elevated level of serum palmitoyl-L-carnitine during aging contributes to AD pathology through these pathways. These findings highlight the significant role of lipid metabolism in neurodegeneration and offer potential therapeutic targets for age-related diseases, including AD.

Abstract 4128491: Dietary N-3 Very-Long-Chain Polyunsaturated Fatty Acids Improve Retinal Function And Reduce Aortic Atherosclerosis In ApoE-Deficient Mice

Introduction: N-3 very-long-chain polyunsaturated fatty acids (VLCPUFA; C≥24), which are found primarily in retina and a few other select tissues, are known to play critical roles in specific biological systems. Although n-3 PUFA, such as eicosapentanoic acid (EPA, C20:5 n-3) and docosahexaenoic acid (DHA, C22:6 n-3), may confer cardiovascular benefits, they did not improve age-related macular degeneration (AMD), a leading cause of blindness worldwide, in clinical trials. The activity of ELOVL fatty acid elongase 2 (ELOVL2), an enzyme that converts EPA into tetracosapentaenoic acid (TPA, C24:5 n-3), is known to decrease in the retina with age due to promoter methylation. Hypothesis: We hypothesized that dietary VLCPUFA may delay or prevent AMD, by bypassing the ELOVL2-mediated lipid elongation step. We also hypothesize that VLCPUFA may benefit cardiometabolic health like shorter-chain n-3 PUFA through similar mechanisms. Aims: We aimed to investigate the effect of dietary VLCPUFA on retinal function and cardiometabolic risk factors in mice. Methods: We have produced a new fish oil that contains ~40% (w/w) of C24-C28-rich VLCPUFA. We fed 9-month-old ApoE -/- mice with normal or VLCPUFA fortified diet (1% or 3% (w/w)) for 8 weeks, and age-matched C57BL/6J mice were used as control. We conducted electroretinography (ERG) and cognitive ability tests at the end of feeding period. In in vitro studies, we performed PPAR reporter assay and investigated the anti-inflammatory effects of TPA in lipopolysaccharide-stimulated RAW264.7 cells. Results: Supplementation of VLCPUFA showed a significant and dose-dependent improvement in ERG response. Like EPA and DHA, we also observed favorable cardiometabolic changes and decreased atherosclerotic plaque area due to dietary VLCPUFA. Intriguingly, VLCPUFA supplemented aging mice exhibit better cognitive performance compared with control. Transcriptome analysis revealed that VLCPUFA-enriched fish oil favorably regulated genes involved in nuclear receptor signaling pathways, lipid metabolism and inflammation. Furthermore, purified TPA potently activates PPARs, and suppressed inflammation in macrophage cells. Conclusions: Overall, our studies revealed for the first time several potential health benefits for our new VLCPUFA-enriched fish oil in several age-related diseases and support its future development as a new dietary supplement.

Abstract 4122350: Most Diabetes Mellitus Patients Had Right Lower Pulmonary Vein Thrombi; Additionally, Many Patients Had Extended Large Rod-Like Thrombi in the Left Atrium

Background: Retrieved thrombus studies have shown that retrieved thrombi have calcifications, indicating that the thrombi are old. Left atrium diverticula (LADs) are common; however, the mechanisms of LAD formation are poorly understood. Pulmonary vein thrombi (PVTs) are common and are underestimated. In 2022, we reported that 98.6% of senior patients with age-related diseases such as hypertension, dyslipidemia and atrial fibrillation had PVTs, as estimated by cardiac computed tomography (CT) and transesophageal echocardiography (TEE). Additionally, we reported a case in which a malignant lymphoma patient had ATs in the right lower pulmonary vein, in which extended large rod-like thrombi in the left atrium (LA) were found, as determined by TEE. Patients with type 2 diabetes mellitus (T2DM) must have PVTs. The characteristics of extended LA thrombi in patients with T2DM are unclear. Methods: Thirty-one patients with T2DM (73.5 +/- 8.9 y.o., from 50 y.o. to 88 y.o.; male, 24) were examined for PVTs, as estimated via TEE and cardiac CT. Results: Thirty (97%) patients with T2DM had PVTs in the right lower pulmonary vein (RLPV) and connected LA thrombi, as estimated using TEE. Among them, 27 (87%) patients had large white rod-like LA thrombi extending from RLPV thrombi, and the diameter of the thin part of the rod-like LA thrombi was approximately 5 mm. The end of the LA thrombi was mainly attached to the left side of the anterior wall or the posterior side of left side wall of the LA. Additionally, there were left atrium diverticula (LADs) around the attachment regions. Three patients had RLPV thrombi and connected shorter LA thrombi. A 79-year-old male patient did not have detectable PVTs. The patient had taken apixaban (2.5 mg, twice daily) for six years due to atrial fibrillation and stroke. Conclusions: Most (97%) elderly T2DM patients had RLPV thrombi. Additionally, many (87%) patients had extended large rod-like thrombi in the LA. The diameter of the thin part of the large rod-like LA thrombi was approximately 5 mm. There were LADs around the attachment regions where the ends of the LA thrombi from the RLPV thrombi were attached.

Abstract 4121348: Impairments in Left Atrioventricular Coupling Underpins Reductions in Skeletal Muscle Mass and Function in Ageing Older Adults

Background: Age-related cardiovascular disease (CVD) may manifest with changes in left ventricular (LV) systolic or left atrial (LA) dysfunction. Alterations in functional performance between the LV and LA chambers characterized by LA-LV coupling may be a sensitive marker representative of impairments in global cardiac performance, compared to either chamber alone. The increasing relevance of skeletal muscle function towards cardiac health in ageing, motivated our current work that investigated associations between skeletal muscle function and LA-LV coupling. Aim : Using advanced cardiac magnetic resonance (CMR) that characterizes cardiac volumetric parameters and strain functions, we determined the association between handgrip strength (HGS) and appendicular lean mass (ALM) with left atrioventricular coupling index (LACI). Methods: Community older adults without CVD underwent simultaneous assessment of HGS by hand dynamometer, height-square adjusted ALM by bio-impedance, and LA phasic function (namely reservoir, conduit, booster strain) as well as LA and LV volumetric parameters by CMR feature tracking. LACI is defined as the ratio of the ratio of LA to LV end-diastolic volumes. We performed linear regression and multivariable logistic regression to examine the relationship between HGS/ALM and LACI. Results: Among 251 study participants (mean age: 71 ± 9.1 years, female 44.7%), 149 (59%) had impaired LACI. HGS was linearly associated with LACI (β=-0.004, p=0.003) and LVEDV (β=1.62, p&lt;0.0001), and ALM was linearly associated with LA volume (β=0.55, p=0.018) and LVEDV (β=3.45, p&lt;0.0001) (Figure.1). Participants with impaired LACI (&gt; 25%) had lower HGS (mean=22.8 ± 7.1 kg vs 26.1 ± 6.4 kg, p= 0.0002), lower ALM (16.4 ± 4.2 kg/m2 vs 17.7 ± 3.8 kg/m2, p=0.014), higher LA volume (36.8 ± 15.2 ml vs 22.0 ± 5.5 ml, p &lt; 0.0001) and lower LV end-diastolic volume (101.0 ± 24.2 ml vs 111.9 ± 27.3 ml, p = 0.0011). The association between impaired LA-LV coupling and lower HGS (β=-0.0647, 95%CI -0.0255, -0.1040, p=0.001) and lower ALM (β=-0.0776, 95%CI -0.0107, -0.1444, p=0.011) persisted after adjusting for age. Conclusion: Reduced HGS and ALM among community-dwelling older adults was associated with impaired LA-LV coupling suggestive of underlying early-stage LA remodelling and impairments in left atrioventricular compliance. Detection of reduced HGS and ALM in community cohorts may prompt early identification of older adults at risk of dysfunctional cardiac aging.

Abstract 4137939: Mosaic loss of Y chromosome is associated with increased all-cause mortality in patients with ST-segment elevation myocardial infarction

Introduction: Mosaic loss of Y chromosome (LOY), a common subtype of somatic mosaicism, is characterized as loss of the entire Y chromosome in a mosaic manner and increases with age. Accumulating evidence has manifested the positive link between LOY and shorter life expectations in elderly men as well as common age-associated diseases, such as cancer and cardiovascular diseases. Experimental studies also demonstrated that hematopoietic LOY in mice induced cardiac fibrosis and led to increased mortality. However, little is known about LOY and prognosis of ST-segment elevation myocardial infarction (STEMI). Hypothesis: We hypothesized that LOY may be associated with lower survival rate of patients with STEMI. Aims: Investigating the impact of LOY in peripheral blood cells on prognosis of patients with STEMI. Methods: This study prospectively enrolled 928 males and 272 females undergoing primary percutaneous coronary intervention for STEMI. LOY was measured in 928 males using droplet digital polymerase chain reaction technique. Results: During a median follow-up of 3.99 years, 93 males (10.0%) and 45 females (16.5%) died. After adjusting for traditional cardiovascular risk factors, the risk of all-cause mortality in males with LOY ≥ 18% (the 90th percentile of LOY) increased to 2.45 (95% confidence intervals [CI]: 1.16–5.15, P = 0.018), 2.11 (95% CI: 1.11–4.01, P = 0.024), and 1.88 (95% CI: 1.02–3.45, P = 0.043) times during 1-, 2-, and 3-year follow-up, respectively, compared to males with LOY &lt; 18%. Among males without prior MI, those with LOY ≥ 18% had an increased risk of all-cause mortality compared to those with LOY &lt; 18% (adjusted hazard ratio 1.93, 95% CI: 1.01–3.67; P = 0.045); this was not observed for males with prior MI. Female patients had a 1.71-fold (95%CI: 1.04–2.81; P = 0.035) increased risk of all-cause mortality than males with LOY &lt; 18%, whereas the risk was similar to males with LOY ≥ 18%. Conclusion: LOY was associated with an increased risk of all-cause mortality in male STEMI patients, particularly in those without prior MI. Detecting LOY in STEMI patients could help further refine sex differences in prognosis and assist in identifying male patients with better prognoses.

Abstract 4129195: Mechanisms of Healthy Aging in the Prevention of Atrial Fibrillation

Introduction: Atrial Fibrillation (AF) is the most frequent cardiac arrhythmia. AF can lead to severe complications such as myocardial infarction, strokes, and sudden death. With 70% of AF patients aged 65 and older, aging stands as the major risk factor for AF. Our group have recently contributed to reveal that old Wistar rats (20 months) are more susceptible to AF than younger rats (5 months). Interestingly, Lou/c/jall (LOU) rats, a model of healthy aging derived from Wistar rats, can live up to ~35 months old (equivalent to 100 human years). LOU rats have been identified as resistant to age-related diseases such as obesity, hypertension, and neurodegenerative disorders, which are major risk factors for AF. However, the susceptibility of LOU rats to AF have never been reported. Hypothesis: LOU rats may carry specific molecular adaptations conferring resistance to age-related cardiac remodeling and low AF vulnerability. Objectives: Characterize the vulnerability of very old LOU rats (32 months) to AF compared to old Wistar rats (22 months). Determine the atrial inflammatory profile of LOU rats and identify the molecular adaptations that may explain their resistance to AF Methods: Male and Female rats were divided into five groups: LOU and Wistar rats of 5 months (young), 20 months (old), and 32 months (very old: LOU/c rats only). AF inducibility was assessed in vivo using transesophageal electrophysiological study and cardiac structure and function were analyzed by in vivo echocardiography. Atrial electrical conduction was examined using ex vivo optical mapping. Histological analyses were performed to assess atrial fibrosis. Additionally, immunoblot analysis, qPCR, and RNA sequencing were employed to investigate the levels of biomarkers involved in atrial inflammation and fibrosis. Result: Old Wistar rats were more vulnerable to AF than young rats. Old and very old LOU were significantly more resistant to AF than old Wistar animals. LOU rats’ low susceptibility to AF was accompanied with absence of cardiac structural and functional remodeling and low levels of atrial fibrosis compared to old Wistar. Additionally, advanced age did not affect LOU rats’ atrial electrical conduction properties as compared to old Wistar rats. Conclusion: Promotion of healthy aging conditions mimicking LOU rats’ resistance to cardiac remodeling and reduction of atrial fibrosis may contribute to prevent AF in subjects with pathological aging.

Inflammaging, a targetable pathway for preventing cardiovascular diseases.

Inflammaging, characterized by persistent chronic inflammation in older adults, has emerged as a critical factor linked to age-related diseases such as cardiovascular diseases (CVDs), metabolic disorders, and cognitive decline, which collectively contribute to the leading causes of death globally. Elevated levels of cytokines, chemokines, and others inflammatory mediators characterize inflammaging and serve as indicators of biological age. Among the causes of inflammaging, deterioration of the immune system, mitochondrial dysfunction, dysbiosis, accumulation of DAMPs, together with genetic or epigenetic factors, contribute to inflammaging not only in CVD but also in other age-related conditions. This review examines the causes and consequences of inflammaging, particularly its implications for atherosclerosis and heart failure with preserved ejection fraction (HFpEF) and explores potential strategies to mitigate it in the onset of CVD.

Amyloid-beta metabolism in age-related neurocardiovascular diseases.

Epidemiological evidence suggests the presence of common risk factors for the development and prognosis of both cardio- and cerebrovascular diseases, including stroke, Alzheimer's disease, vascular dementia, heart, and peripheral vascular diseases. Accumulation of harmful blood signals may induce organotypic endothelial dysfunction affecting blood-brain barrier function and vascular health in age-related diseases. Genetic-, age-, lifestyle- or cardiovascular therapy-associated imbalance of amyloid-beta (Aβ) peptide metabolism in the brain and periphery may be the missing link between age-related neurocardiovascular diseases. Genetic polymorphisms of genes related to Aβ metabolism, lifestyle modifications, drugs used in clinical practice, and Aβ-specific treatments may modulate Aβ levels, affecting brain, vascular, and cardiac diseases. This narrative review elaborates on the effects of interventions on Aβ metabolism in the brain, cerebrospinal fluid, blood, and peripheral heart or vascular tissues. Implications for clinical applicability, gaps in knowledge, and future perspectives of Aβ as the link among age-related neurocardiovascular diseases are also discussed.