Publications by authors named "Barzilai N"
Background: Motoric Cognitive Risk (MCR) syndrome is a predementia syndrome characterized by slow gait and subjective cognitive concerns. Individuals with MCR are at high risk of transitioning to both Alzheimer's disease (AD) and vascular dementia. With chronological age, the incidence of MCR increases and MCR cases exhibit a higher prevalence of age-associated diseases.
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- Around 40% of older adults (65+) face memory loss, particularly in episodic memory, raising the need to explore its genetic reasons.* -
- A study of 742 Ashkenazi Jewish individuals revealed links between episodic memory decline and rare genetic variants in the ITSN1 and CRHR2 genes, alongside common Alzheimer's polygenic risk.* -
- The findings suggest that different memory-related issues can arise from rare variants, highlighting new genetic risk factors and the need to understand the biological processes behind them.*
Article Synopsis
- Researchers examined the impact of rare loss-of-function mutations on longevity, focusing on Ashkenazi Jewish centenarians using whole-exome sequencing.
- Centenarians showed a significantly lower burden of LOF mutations (11-22%) compared to control individuals, and this effect was also seen in their offspring.
- The study identified 35 genes with fewer LOF mutations in centenarians, highlighting RGP1, PCNX2, and ANO9 as key longevity genes that positively affect aging-related traits and gene expression changes over time.
Article Synopsis
- Recent advancements in aging research and drug discovery connect basic research with clinical applications, aiming to promote healthy longevity in humans.* -
- The Aging Research and Drug Discovery Meeting in 2023 highlighted key areas such as AI, biomarkers, geroscience, and clinical trials focused on enhancing healthspan.* -
- The meeting emphasized the importance of combining generative AI with innovative biological technologies to tackle age-related diseases and extend healthy lifespans.*
Diminished signaling via insulin/insulin-like growth factor-1 (IGF-1) axis is associated with longevity in different model organisms. IGF-1 gene is highly conserved across species, with only few evolutionary changes identified in it. Despite its potential role in regulating lifespan, no coding variants in IGF-1 have been reported in human longevity cohorts to date.
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- Biomarkers of aging (BOA) are special measurements that can help scientists understand how old someone is on a biological level and how this changes with treatments.
- Recently, many new BOA have been discovered that could really help people live healthier lives as they age, but there are some problems getting these ideas into actual medical practice.
- Experts found six main challenges that are stopping BOA from being used more widely and suggested ways to make them better, such as ensuring they are easy to access and useful for everyone.
Article Synopsis
- - The study investigates how multiple genetic variants, influenced by pleiotropy (where one gene affects multiple traits), contribute to human longevity by analyzing factors like lipid metabolism, BMI, and cognitive performance through genetic data from the UK Biobank.
- - Researchers created an integrated longevity genetic score (iLGS) to identify individuals with exceptional longevity, and their model showed that those in the highest decile could live an average of 4.8 years longer than others.
- - The study also found protein markers linked to exceptional longevity and suggested potential drug repurposing for aging therapies, offering a new way to assess longevity and identify individuals at risk of early mortality.
Introduction: Motoric cognitive risk (MCR) and amnestic mild cognitive impairment (aMCI) syndromes are each reliable predictors of incident Alzheimer's disease (AD), but MCR may be a stronger predictor of vascular dementia than AD. This study contrasted cortical and hippocampal atrophy patterns in MCR and aMCI.
Methods: Cross-sectional data from 733 older adults without dementia or disability (M age = 73.
Introduction: Slow gait speed is associated with poor health outcomes in aging, but the relationship between cerebral small vessel disease (CSVD) pathologies and gait speed in aging is not well understood. We investigated the relationships between CSVD imaging markers and gait speed during simple (normal pace walking [NPW]) and complex (walking while talking [WWT]) as both measures are associated with shared health outcomes such as falls, frailty, disability, mortality, and dementia.
Methods: A total of 113 Ashkenazi Jewish adults over 65 (M age = 78.
Article Synopsis
- The hypothalamus plays a crucial role in maintaining homeostasis and is linked to aging, with changes observed in mouse models leading to cognitive decline.
- A study involving older adults used advanced imaging to explore the relationship between hypothalamic microstructure and neurocognitive factors, revealing that changes in mean diffusivity were age-related and correlated with decreased cortical thickness.
- The research found that lower levels of fractional anisotropy in the hypothalamus may predict cognitive decline over time, marking the first evidence of a direct link between hypothalamic structure and cognitive aging in humans.
Article Synopsis
- - Approximately 40% of individuals over 65 experience memory loss, particularly affecting episodic memory, emphasizing the need to understand the genetic factors behind this decline.
- - The research involved analyzing genetic variants in 742 older Ashkenazi Jewish participants, employing all-atom molecular dynamics simulations to explore the mechanisms associated with episodic memory decline.
- - Findings revealed both common genetic risks for Alzheimer's Disease and unique rare variants linked to memory issues, highlighting different underlying mechanisms that could lead to varying memory pathologies.
Cognition and gait share brain substrates in aging and dementia. Cognitive reserve (CR) allows individuals to cope with brain pathology and delay cognitive impairment and dementia. Yet, evidence for that CR is associated with age-related cognitive decline is mixed, and evidence for that CR is associated with age-related gait decline is limited.
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- - The study investigates genomic changes, specifically copy number variants (CNVs), in a cohort of Ashkenazi Jewish centenarians, their children, and unrelated controls, to understand factors influencing longevity.
- - Among 670 participants, it was found that centenarians had more total CNVs compared to controls, but they retained better genomic integrity, indicated by a lower total length of lost genomic material.
- - The research also revealed that offspring had the highest number of unique CNVs, which may contribute to longevity preservation, with significant genomic regions linked to crucial biological functions identified.
The APOE4 allele is recognized as a significant genetic risk factor to Alzheimer's disease (AD) and influences longevity. Nonetheless, some APOE4 carriers exhibit resistance to AD even in advanced age. Humanin, a mitochondrial-derived peptide comprising 24 amino acids, has variants linked to cognitive resilience and longevity.
View Article and Find Full Text PDFObjective: This study examines the plasma proteomic profile of abdominal obesity in older adults.
Methods: The association of abdominal obesity (waist circumference [WC]) with 4265 plasma proteins identified using the SomaScan Assay was examined in 969 Ashkenazi Jewish participants (LonGenity cohort), aged 65 years and older (mean [SD] age 75.7 [6.
Article Synopsis
- The search for biomarkers that measure biological aging, especially 'omic'-based ones, has gained momentum, aiming to predict aging outcomes and assess interventions for healthy aging.
- There is currently no agreement on the best methods to validate these aging biomarkers before using them in clinical settings.
- The review emphasizes the need for systematic validation, which can enhance the reliability and effectiveness of aging biomarkers in clinical research and trials focused on longevity.
Article Synopsis
- * The researchers identified 34 genetic variants linked to traits like lipid metabolism and cognitive performance, and developed a composite polygenic score to better understand and predict lifespan variations among individuals.
- * Their model showed that individuals in the top 10% of the longevity score could live nearly 5 years longer on average, leading to insights on potential drug repurposing for longevity interventions and offering a framework for identifying individuals at higher risk of mortality based on their genetic profile.
Animal studies show aging varies between individuals as well as between organs within an individual, but whether this is true in humans and its effect on age-related diseases is unknown. We utilized levels of human blood plasma proteins originating from specific organs to measure organ-specific aging differences in living individuals. Using machine learning models, we analysed aging in 11 major organs and estimated organ age reproducibly in five independent cohorts encompassing 5,676 adults across the human lifespan.
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- The growth of aging biology research is focusing on finding and assessing longevity interventions for humans, making biomarkers of aging essential tools for these efforts.
- A lack of standards and consensus on what makes a reliable aging biomarker currently limits their development and application in clinical settings.
- The article proposes a framework for categorizing aging biomarkers, discussing validation processes, and identifying challenges that need future research to facilitate their use in clinical trials and practices.
Article Synopsis
- - Genome-wide association studies have identified the 9p21.3 chromosomal locus as a key area linked to several age-related diseases such as heart disease, cancer, and diabetes.
- - Research involving 450 centenarians and 500 healthy controls from the Ashkenazi Jewish population revealed a significant reduction in genetic risk factors for these diseases among the centenarians.
- - The study suggests that individuals who live to be 100 or older potentially possess a unique genetic profile, resulting in lower risks of developing multiple age-related disorders linked to the 9p21.3 region.
Geroscience is becoming a major hope for preventing age-related diseases and loss of function by targeting biological mechanisms of aging. This unprecedented paradigm shift requires optimizing the design of future clinical studies related to aging in humans. Researchers will face a number of challenges, including ideal populations to study, which lifestyle and Gerotherapeutic interventions to test initially, selecting key primary and secondary outcomes of such clinical trials, and which age-related biomarkers are most valuable for both selecting interventions and predicting or monitoring clinical responses ("Gerodiagnostics").
View Article and Find Full Text PDFAssociation of a Blood-Based Aging Biomarker Index With Death and Chronic Disease: Cardiovascular Health Study.
J Gerontol A Biol Sci Med Sci
February 2024
Background: A goal of gerontology is to discover phenotypes that reflect biological aging distinct from disease pathogenesis. Biomarkers that are strongly associated with mortality could be used to define such a phenotype. However, the relation of such an index with multiple chronic conditions warrants further exploration.
View Article and Find Full Text PDFGeroscience posits that cardiovascular disease (CVD) and other chronic diseases result from progressive erosion of the effectiveness of homeostatic mechanisms that oppose age-related accumulation of molecular damage. This hypothetical common root to chronic diseases explains why patients with CVD are often affected by multimorbidity and frailty and why older age negatively affects CVD prognosis and treatment response. Gerotherapeutics enhance resilience mechanisms that counter age-related molecular damage to prevent chronic diseases, frailty, and disability, thereby extending healthspan.
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