scholarly journals THE LONGEVITY CONSORTIUM VISION

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S208-S209
Author(s):  
Daniel S Evans ◽  
Daniel S Evans ◽  
Steven R Cummings ◽  
Nicholas Schork
Keyword(s):  
Healthy Aging ◽  
Human Longevity ◽  
Cooperative Research ◽  
Healthy Human ◽  
Molecular Features ◽  
Human Lifespan ◽  
Age Related ◽  
Show Evidence ◽  
Funding Opportunities ◽  
Multiple Chronic Diseases

Abstract Molecular factors and pathways promoting human longevity and healthy aging can potentially delay or prevent multiple chronic diseases and conditions, but identifying such factors that can be pharmacologically targeted requires an integrated multidisciplinary approach. We describe the design of the five research projects and three cores of the Longevity Consortium (LC) and how their cooperative research is designed to discover molecular factors and pathways that can predict healthy human aging and longevity, associate with extreme human lifespan, show relevance to chronic age-related conditions, respond to interventions to slow aging in mice, and show evidence for association with lifespan across species. A systems biology approach is undertaken to identify common molecular features across human traits and organisms, and a chemoinformatics approach to link molecular targets to candidate healthy aging interventions. The LC results are made publicly available and we provide funding opportunities to the scientific community to support pilot projects.

scholarly journals Resveratrol: A Sirtuin Activator and The Fountain of Youth

2015 ◽  
Vol 7 (1) ◽  
pp. 1 ◽  
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya
Keyword(s):  
Caloric Restriction ◽  
Healthy Aging ◽  
Myocardial Infarct ◽  
Functional Decline ◽  
Steady Increase ◽  
Healthy Human ◽  
Aging Research ◽  
Human Lifespan ◽  
Age Related ◽  
Fountain Of Youth

BACKGROUND: An organism’s lifespan is inevitably accompanied by the aging process, which involves functional decline, a steady increase of a plethora of chronic diseases, and ultimately death. Thus, it has been an ongoing dream of mankind to improve healthspan and extend life.CONTENT: There are only a few proposed aging interventions: caloric restriction, exercise, and the use of low-molecular-weight compounds, including spermidine, metformin, resveratrol, and rapamycin. Resveratrol, a constituent of red wine, has long been suspected to have cardioprotective effects. Interest in this compound has been renewed in recent years, first from its identification as a chemopreventive agent for skin cancer, and subsequently from reports that it activates sirtuin deacetylases and extends the lifespans of lower organisms. Resveratrol have been shown to prevent and reduce the severity of age-related diseases such as atherosclerosis, stroke, myocardial infarct, diabetes, neurodegenerative diseases, osteoarthritis, tumors and metabolic syndrome, along with their ability to extend lifespan.SUMMARY: The purpose of aging research is the identification of interventions that may avoid or ameliorate the ravages of time. In other words, the quest is for healthy aging, where improved longevity is coupled to a corresponding healthspan extension. It is only by extending the healthy human lifespan that we will truly meet the premise of the Roman poet Cicero: “No one is so old as to think that he may not live a year.”KEYWORDS: aging, caloric restriction, mimetic, healthspan, sirtuin activator

A metabolomic aging clock using human CSF

2021 ◽  
Author(s):  
Nathan Hwangbo ◽  
Xinyu Zhang ◽  
Daniel Raftery ◽  
Haiwei Gu ◽  
Shu-Ching Hu ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Healthy Aging ◽  
Prediction Models ◽  
Mass Spectrometry Analysis ◽  
Chronological Age ◽  
Healthy Human ◽  
Missing Data Imputation ◽  
Spectrometry Analysis ◽  
Residual Variation ◽  
Age Related

Abstract Quantifying the physiology of aging is essential for improving our understanding of age-related disease and the heterogeneity of healthy aging. Recent studies have shown that in regression models using “-omic” platforms to predict chronological age, residual variation in predicted age is correlated with health outcomes, and suggest that these “omic clocks” provide measures of biological age. This paper presents predictive models for age using metabolomic profiles of cerebrospinal fluid from healthy human subjects, and finds that metabolite and lipid data are generally able to predict chronological age within 10 years. We use these models to predict the age of a cohort of subjects with Alzheimer’s and Parkinson’s disease and find an increase in prediction error, potentially indicating that the relationship between the metabolome and chronological age differs with these diseases. However, evidence is not found to support the hypothesis that our models will consistently over-predict the age of these subjects. In our analysis of control subjects, we find the carnitine shuttle, sucrose, biopterin, vitamin E metabolism, tryptophan, and tyrosine to be the most associated with age. We showcase the potential usefulness of age prediction models in a small dataset (n = 85), and discuss techniques for drift correction, missing data imputation, and regularized regression, which can be used to help mitigate the statistical challenges that commonly arise in this setting. To our knowledge, this work presents the first multivariate predictive metabolomic and lipidomic models for age using mass spectrometry analysis of cerebrospinal fluid.

Aging of the Retina: Molecular and Metabolic Turbulences and Potential Interventions

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Laura Campello ◽  
Nivedita Singh ◽  
Jayshree Advani ◽  
Anupam K. Mondal ◽  
Ximena Corso-Diaz ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Cell Types ◽  
Lifestyle Changes ◽  
Annual Review ◽  
Past Century ◽  
Publication Date ◽  
Vision Science ◽  
Human Lifespan ◽  
Cellular Events ◽  
Age Related

Multifaceted and divergent manifestations across tissues and cell types have curtailed advances in deciphering the cellular events that accompany advanced age and contribute to morbidities and mortalities. Increase in human lifespan during the past century has heightened awareness of the need to prevent age-associated frailty of neuronal and sensory systems to allow a healthy and productive life. In this review, we discuss molecular and physiological attributes of aging of the retina, with a goal of understanding age-related impairment of visual function. We highlight the epigenome–metabolism nexus and proteostasis as key contributors to retinal aging and discuss lifestyle changes as potential modulators of retinal function. Finally, we deliberate promising intervention strategies for promoting healthy aging of the retina for improved vision. Expected final online publication date for the Annual Review of Vision Science, Volume 7 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals IDENTIFICATION OF ADAMTS7 AND CEACAM19 AS CANDIDATE HEALTHY AGING ASSOCIATED GENES

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S102-S102
Author(s):  
Daniel S Evans ◽  
Steven R Cummings
Keyword(s):  
Lung Function ◽  
Cohort Studies ◽  
Multiple Testing ◽  
Healthy Aging ◽  
Forced Expiratory Volume ◽  
Healthy Human ◽  
Total N ◽  
Markers Of Inflammation ◽  
Translational Strategies ◽  
Funding Opportunities

Abstract The goals of the Longevity Genomics research group (www.longevitygenomics.org) are to develop translational strategies to promote healthy human aging based on findings from genomic studies of aging. Our investigation began with the previously reported and publicly available GWAS of the top 10% of parental lifespan in the UK Biobank, reported by Pilling et al. From five loci reported by Pilling et al., 61 candidate longevity-associated genes (LAGs) were identified using FUMA software. We then tested the 61 candidate genes for aging-related trait associations with tissue-specific predicted gene expression in cohort studies of elderly participants using PrediXcan. PrediXcan was applied to three longitudinal cohort studies of elderly individuals: Health ABC, MrOS, and SOF with a total N of 9893 participants. Aging outcomes tested for association were in the following categories: survival and lifespan, kidney function, cognitive function, physical performance tests, self-reported health and disability, diabetes-related traits, cardiovascular-related traits, lung function, and markers of inflammation. After correction for multiple testing, two genes were significantly associated with longevity-related outcomes. Predicted expression of CEACAM19 in the aorta was significantly associated with circulating C-reactive protein (CRP) levels. In addition, predicted expression of ADAMTS7 in the spleen was associated with a measure of lung function, the forced expiratory volume in the first second. Biological mechanisms for these associations are proposed, and our project provides funding opportunities for interested scientists to follow-up these results with laboratory studies (www.longevitygenomics.org/funding).

scholarly journals The Three Genetics (Nuclear DNA, Mitochondrial DNA, and Gut Microbiome) of Longevity in Humans Considered as Metaorganisms

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Paolo Garagnani ◽  
Chiara Pirazzini ◽  
Cristina Giuliani ◽  
Marco Candela ◽  
Patrizia Brigidi ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Nuclear Dna ◽  
Complex Dynamics ◽  
Nuclear Genome ◽  
Holistic Approach ◽  
Human Longevity ◽  
Human Lifespan ◽  
Complex Interactions ◽  
Age Related

Usually the genetics of human longevity is restricted to the nuclear genome (nDNA). However it is well known that the nDNA interacts with a physically and functionally separated genome, the mitochondrial DNA (mtDNA) that, even if limited in length and number of genes encoded, plays a major role in the ageing process. The complex interplay between nDNA/mtDNA and the environment is most likely involved in phenomena such as ageing and longevity. To this scenario we have to add another level of complexity represented by the microbiota, that is, the whole set of bacteria present in the different part of our body with their whole set of genes. In particular, several studies investigated the role of gut microbiota (GM) modifications in ageing and longevity and an age-related GM signature was found. In this view, human being must be considered as “metaorganism” and a more holistic approach is necessary to grasp the complex dynamics of the interaction between the environment and nDNA-mtDNA-GM of the host during ageing. In this review, the relationship between the three genetics and human longevity is addressed to point out that a comprehensive view will allow the researchers to properly address the complex interactions that occur during human lifespan.

scholarly journals Linked deterioration of early visual perception, function and structure in healthy human aging

2020 ◽  
Author(s):  
Maria Fatima Silva ◽  
Ben M Harvey ◽  
Lília Jorge ◽  
Nádia Canário ◽  
Fátima Machado ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Visual Field ◽  
Visual Perception ◽  
Healthy Aging ◽  
Healthy Human ◽  
Cortical Structure ◽  
Surface Areas ◽  
Structural Deterioration ◽  
Age Related ◽  
Retinal Structure

SummaryLow-level visual perception deteriorates during healthy aging. We hypothesized that age-related retinal and cortical structure deteriorations affect perception through specific disruptions of neural function. We measured perceptual visual acuity in fifty healthy adults aged 20-80 years. We then measured these participants’ early visual field map (V1, V2 and V3) functional population receptive field (pRF) sizes and structural surface areas using fMRI, and their retinal structure using high-definition optical coherence tomography. With increasing age visual acuity decreased, pRF sizes increased, visual field maps surface areas decreased, and retinal thickness decreased. Among these measures, only functional pRF sizes predicted perceptual visual acuity. PRF sizes were in turn predicted by cortical structure only (surface areas), which were only predicted by retinal structure (thickness). We propose that age-related retinal structural deterioration disrupts cortical structure, thereby disrupting cortical functional neural interactions that normally sharpen visual position selectivity: the resulting functional disruption underlies age-related perceptual deterioration.

scholarly journals Footprints in the Sand: Deep Taxonomic Comparisons in Vertebrate Genomics to Unveil the Genetic Programs of Human Longevity

2021 ◽  
Vol 12 ◽  
Author(s):  
Stephen Treaster ◽  
David Karasik ◽  
Matthew P. Harris
Keyword(s):  
Meta Analysis ◽  
Population Level ◽  
Human Longevity ◽  
Comparative Genomic ◽  
Human Populations ◽  
Key Factors ◽  
Genetic Constraints ◽  
Genomic Signatures ◽  
Human Lifespan ◽  
Age Related

With the modern quality, quantity, and availability of genomic sequencing across species, as well as across the expanse of human populations, we can screen for shared signatures underlying longevity and lifespan. Knowledge of these mechanisms would be medically invaluable in combating aging and age-related diseases. The diversity of longevities across vertebrates is an opportunity to look for patterns of genetic variation that may signal how this life history property is regulated, and ultimately how it can be modulated. Variation in human longevity provides a unique window to look for cases of extreme lifespan within a population, as well as associations across populations for factors that influence capacity to live longer. Current large cohort studies support the use of population level analyses to identify key factors associating with human lifespan. These studies are powerful in concept, but have demonstrated limited ability to resolve signals from background variation. In parallel, the expanding catalog of sequencing and annotation from diverse species, some of which have evolved longevities well past a human lifespan, provides independent cases to look at the genomic signatures of longevity. Recent comparative genomic work has shown promise in finding shared mechanisms associating with longevity among distantly related vertebrate groups. Given the genetic constraints between vertebrates, we posit that a combination of approaches, of parallel meta-analysis of human longevity along with refined analysis of other vertebrate clades having exceptional longevity, will aid in resolving key regulators of enhanced lifespan that have proven to be elusive when analyzed in isolation.

Exercise tames the wild side of the Myc network: a hypothesis

2012 ◽  
Vol 303 (1) ◽  
pp. E18-E30 ◽  
Author(s):  
Kishorchandra Gohil ◽  
George A. Brooks
Keyword(s):  
Stem Cell ◽  
Primary Source ◽  
Physical Activities ◽  
Healthy Human ◽  
Human Lifespan ◽  
Age Related ◽  
Mitochondrial Functions ◽  
Cardiovascular Pathologies ◽  
Exercise Induced ◽  
Cell Growth And Proliferation

We propose that the well-documented therapeutic actions of repeated physical activities over human lifespan are mediated by the rapidly turning over proto-oncogenic Myc (myelocytomatosis) network of transcription factors. This transcription factor network is unique in utilizing promoter and epigenomic (acetylation/deacetylation, methylation/demethylation) mechanisms for controlling genes that include those encoding intermediary metabolism (the primary source of acetyl groups), mitochondrial functions and biogenesis, and coupling their expression with regulation of cell growth and proliferation. We further propose that remote functioning of the network occurs because there are two arms of this network, which consists of driver cells (e.g., working myocytes) that metabolize carbohydrates, fats, proteins, and oxygen and produce redox-modulating metabolites such as H2O2, NAD+, and lactate. The exercise-induced products represent autocrine, paracrine, or endocrine signals for target recipient cells (e.g., aortic endothelium, hepatocytes, and pancreatic β-cells) in which the metabolic signals are coupled with genomic networks and interorgan signaling is activated. And finally, we propose that lactate, the major metabolite released from working muscles and transported into recipient cells, links the two arms of the signaling pathway. Recently discovered contributions of the Myc network in stem cell development and maintenance further suggest that regular physical activity may prevent age-related diseases such as cardiovascular pathologies, cancers, diabetes, and neurological functions through prevention of stem cell dysfunctions and depletion with aging. Hence, regular physical activities may attenuate the various deleterious effects of the Myc network on health, the wild side of the Myc-network, through modulating transcription of genes associated with glucose and energy metabolism and maintain a healthy human status.

scholarly journals An aging clock using metabolomic CSF

2021 ◽  
Author(s):  
Nathan Hwangbo ◽  
Xinyu Zhang ◽  
Daniel Raftery ◽  
Haiwei Gu ◽  
Shu-Ching Hu ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Healthy Aging ◽  
Prediction Models ◽  
Mass Spectrometry Analysis ◽  
Chronological Age ◽  
Healthy Human ◽  
Missing Data Imputation ◽  
Spectrometry Analysis ◽  
Residual Variation ◽  
Age Related

Quantifying the physiology of aging is essential for improving our understanding of age-related disease and the heterogeneity of healthy aging. Recent studies have shown that in regression models using "-omic" platforms to predict chronological age, residual variation in predicted age is correlated with health outcomes, and suggest that these "omic clocks" provide measures of biological age. This paper presents predictive models for age using metabolomic profiles of cerebrospinal fluid from healthy human subjects, and finds that metabolite and lipid data are generally able to predict chronological age within 10 years. We use these models to predict the age of a cohort of subjects with Alzheimer's and Parkinson's disease and find an increase in prediction error, potentially indicating that the relationship between the metabolome and chronological age differs with these diseases. In our analysis of control subjects, we find the carnitine shuttle, sucrose, biopterin, vitamin E metabolism, tryptophan, and tyrosine to be the most associated with age. We showcase the potential usefulness of age prediction models in a small dataset (n = 85), and discuss techniques for drift correction, missing data imputation, and regularized regression which can be used to help mitigate the statistical challenges that commonly arise in this setting. To our knowledge, this work presents the first multivariate predictive metabolomic and lipidomic models for age using mass spectrometry analysis of cerebrospinal fluid.

scholarly journals PROLONGATION OF HUMAN LIFESPAN BY IMMATURE PEAR EXTRACT MEDIATED SIRTUIN-RELATED GENE EXPRESSION

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S97-S97
Author(s):  
Akira Ogita ◽  
Wakae Murata ◽  
Marina Hasegawa ◽  
Ken Yamauchi ◽  
Akiko Sakai ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Mammalian Cells ◽  
Human Genetics ◽  
Human Life ◽  
Yeast Cells ◽  
Aging Effects ◽  
Healthy Human ◽  
Chronological Lifespan ◽  
Human Lifespan ◽  
Age Related

Abstract Demographics of the world are changing rapidly with older populations growing at an unprecedented rate. Cellular senescence, a decline of cellular function due to aging, causes gradual loss of physiological functions. Several cellular senescence-related chronic diseases, such as metabolic syndrome, cardiovascular disease, cancer, osteoporosis, diabetes, and hypertension, negatively affect the quality of human life. Intervention in the cellular senescence process may reduce these incidences and slow the progression of age-related diseases, while contributing to the longevity of healthy human lifespans. Saccharomyces cerevisiae, the budding yeast, is a simple model system that can provide significant insights into the human genetics and molecular biology of senescence and is considered suitable as a cellular model for research on mammalian cells. The aim of our study was to investigate the anti-aging effects of immature pear fruit extract (IPE) on yeast cells and its possible application to extend healthy lifespan in humans. Anti-aging effects of IPE were investigated using a chronological lifespan assay on S. cerevisiae cells. The chronological lifespan of the yeast treated with IPE at 1% (v/v) was significantly extended than that of untreated cells (p < 0.05). The expression of sirtuin-related genes, which regulate cellular senescence, was examined by reverse transcription-polymerase chain reaction and found to be significantly increased following IPE treatment. These results suggest that sirtuin-related genes have important roles in IPE-regulated lifespan extension, which provides a mechanism by which IPE could affect mammalian cells and potentially extend healthy human lifespans.

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