scholarly journals New Computational Approaches to Aging Research

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 736-736
Author(s):  
Morgan E Levine
Keyword(s):  
Aging Process ◽  
Molecular Level ◽  
Biological Aging ◽  
Systems Dynamics ◽  
Learning Approaches ◽  
Biological Organization ◽  
Aging Research ◽  
Biomarkers Of Aging ◽  
Age Related ◽  
Novel Biomarkers

Abstract Aging is associated with numerous changes at all levels of biological organization. Harnessing this information to develop measures that accurately and reliably quantify the biological aging process will require systems biology approaches. This talk will illustrate how epigenetic data can be integrated with cellular, physiological, proteomic, and clinical data to model age-related changes that propagate up the levels—finally manifesting as age-related disease or death. I will also describe how network modeling and machine learning approaches (linear and non-linear) can be used to identify causal features in aging from which to generate novel biomarkers. Given the complexity of the biological aging process, modeling of systems dynamics over time will both lead to the development of better biomarkers of aging, and also inform our conceptualization of how alterations at the molecular level propagate up levels of organization to eventually influence morbidity and mortality risk.

scholarly journals SYSTEMS-LEVEL MODELING OF BIOLOGICAL AND MOLECULAR AGING CHANGES OVER TIME

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S579-S579
Author(s):  
Morgan E Levine ◽  
Perry Kuo ◽  
Jennifer Schrack ◽  
Eleanor M Simonsick ◽  
Susan Resnick ◽  
...  
Keyword(s):  
Aging Process ◽  
Biological Aging ◽  
Systems Dynamics ◽  
Epigenetic Alterations ◽  
Biological Organization ◽  
Biomarkers Of Aging ◽  
Baltimore Longitudinal Study ◽  
Using Data ◽  
Changes Over Time ◽  
Over Time

Abstract Aging is associated with numerous changes at all levels of biological organization. Harnessing this information to develop measures that accurately and reliably quantify the biological aging process will require longitudinal modeling and incorporation of systems level approaches. We will describe applications of network modeling for longitudinal multi-system biomarker data. Using data from the Baltimore Longitudinal Study of Aging (BLSA) we are able to generate systems level models of biological and physiological function, and then demonstrate how these networks change with age. We will also link systems-level aging changes to hallmarks of aging, including epigenetic alterations, senescence, mitochondrial dysfunction, and proteostasis. Given the complexity of the biological aging process, modeling of systems dynamics over time will both lead to the development of better biomarkers of aging, and also inform our conceptualization of how alterations at the molecular level propagate up levels of organization to eventually influence morbidity and mortality risk.

Individual DNA Methylation Profile is Correlated with Age and can be Targeted to Modulate Healthy Aging and Longevity

2019 ◽  
Vol 25 (39) ◽  
pp. 4139-4149 ◽  
Author(s):  
Francesco Guarasci ◽  
Patrizia D'Aquila ◽  
Alberto Montesanto ◽  
Andrea Corsonello ◽  
Dina Bellizzi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Mitochondrial Dna ◽  
Aging Process ◽  
Healthy Aging ◽  
Nuclear Dna ◽  
Epigenetic Modification ◽  
Biological Aging ◽  
Biomarkers Of Aging ◽  
Age Related

: Patterns of DNA methylation, the best characterized epigenetic modification, are modulated by aging. In humans, different studies at both site-specific and genome-wide levels have reported that modifications of DNA methylation are associated with the chronological aging process but also with the quality of aging (or biological aging), providing new perspectives for establishing powerful biomarkers of aging. : In this article, the role of DNA methylation in aging and longevity has been reviewed by analysing literature data about DNA methylation variations occurring during the lifetime in response to environmental factors and genetic background, and their association with the aging process and, in particular, with the quality of aging. Special attention has been devoted to the relationship between nuclear DNA methylation patterns, mitochondrial DNA epigenetic modifications, and longevity. Mitochondrial DNA has recently been reported to modulate global DNA methylation levels of the nuclear genome during the lifetime, and, in spite of the previous belief, it has been found to be the target of methylation modifications. : Analysis of DNA methylation profiles across lifetime shows that a remodeling of the methylome occurs with age and/or with age-related decline. Thus, it can be an excellent biomarker of aging and of the individual decline and frailty status. The knowledge about the mechanisms underlying these modifications is crucial since it might allow the opportunity for targeted treatment to modulate the rate of aging and longevity.

scholarly journals The use of DNA methylation clock in aging research

2020 ◽  
pp. 153537022096880
Author(s):  
Xi He ◽  
Jiaojiao Liu ◽  
Bo Liu ◽  
Jingshan Shi
Keyword(s):  
Dna Methylation ◽  
Methylation Status ◽  
Biological Aging ◽  
Subjective Age ◽  
Aging Research ◽  
Risk Of Death ◽  
Biomarkers Of Aging ◽  
Progressive Loss ◽  
Key Characteristics ◽  
Novel Biomarkers

One of the key characteristics of aging is a progressive loss of physiological integrity, which weakens bodily functions and increases the risk of death. A robust biomarker is important for the assessment of biological age, the rate of aging, and a person's health status. DNA methylation clocks, novel biomarkers of aging, are composed of a group of cytosine-phosphate-guanine dinucleotides, the DNA methylation status of which can be used to accurately measure subjective age. These clocks are considered accurate biomarkers of chronological age for humans and other vertebrates. Numerous studies have demonstrated these clocks to quantify the rate of biological aging and the effects of longevity and anti-aging interventions. In this review, we describe the purpose and use of DNA methylation clocks in aging research.

scholarly journals Omics in a Digital World: The Role of Bioinformatics in Providing New Insights Into Human Aging

2021 ◽  
Vol 12 ◽  
Author(s):  
Serena Dato ◽  
Paolina Crocco ◽  
Nicola Rambaldi Migliore ◽  
Francesco Lescai
Keyword(s):  
High Throughput ◽  
Aging Process ◽  
Single Cell Analysis ◽  
Physiological Age ◽  
Data Types ◽  
Aging Research ◽  
Digital World ◽  
Age Related ◽  
Critical Issues ◽  
The Individual

BackgroundAging is a complex phenotype influenced by a combination of genetic and environmental factors. Although many studies addressed its cellular and physiological age-related changes, the molecular causes of aging remain undetermined. Considering the biological complexity and heterogeneity of the aging process, it is now clear that full understanding of mechanisms underlying aging can only be achieved through the integration of different data types and sources, and with new computational methods capable to achieve such integration.Recent AdvancesIn this review, we show that an omics vision of the age-dependent changes occurring as the individual ages can provide researchers with new opportunities to understand the mechanisms of aging. Combining results from single-cell analysis with systems biology tools would allow building interaction networks and investigate how these networks are perturbed during aging and disease. The development of high-throughput technologies such as next-generation sequencing, proteomics, metabolomics, able to investigate different biological markers and to monitor them simultaneously during the aging process with high accuracy and specificity, represents a unique opportunity offered to biogerontologists today.Critical IssuesAlthough the capacity to produce big data drastically increased over the years, integration, interpretation and sharing of high-throughput data remain major challenges. In this paper we present a survey of the emerging omics approaches in aging research and provide a large collection of datasets and databases as a useful resource for the scientific community to identify causes of aging. We discuss their peculiarities, emphasizing the need for the development of methods focused on the integration of different data types.Future DirectionsWe critically review the contribution of bioinformatics into the omics of aging research, and we propose a few recommendations to boost collaborations and produce new insights. We believe that significant advancements can be achieved by following major developments in bioinformatics, investing in diversity, data sharing and community-driven portable bioinformatics methods. We also argue in favor of more engagement and participation, and we highlight the benefits of new collaborations along these lines. This review aims at being a useful resource for many researchers in the field, and a call for new partnerships in aging research.

scholarly journals Senescence and aging: Causes, consequences, and therapeutic avenues

2017 ◽  
Vol 217 (1) ◽  
pp. 65-77 ◽  
Author(s):  
Domhnall McHugh ◽  
Jesús Gil
Keyword(s):  
Neurodegenerative Disorders ◽  
Cellular Response ◽  
Aging Process ◽  
Normal Development ◽  
Growth Arrest ◽  
The Novel ◽  
Aging Research ◽  
Related Disease ◽  
Age Related ◽  
Stable Growth

Aging is the major risk factor for cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. Although we are far from understanding the biological basis of aging, research suggests that targeting the aging process itself could ameliorate many age-related pathologies. Senescence is a cellular response characterized by a stable growth arrest and other phenotypic alterations that include a proinflammatory secretome. Senescence plays roles in normal development, maintains tissue homeostasis, and limits tumor progression. However, senescence has also been implicated as a major cause of age-related disease. In this regard, recent experimental evidence has shown that the genetic or pharmacological ablation of senescent cells extends life span and improves health span. Here, we review the cellular and molecular links between cellular senescence and aging and discuss the novel therapeutic avenues that this connection opens.

scholarly journals Age-Associated Epigenetic Alterations, Somatic Mutations, and Their Crosstalk in Alzheimer’s Disease

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 636-637
Author(s):  
Yaroslav Markov ◽  
Kyra Thrush ◽  
Morgan Levine
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Somatic Mutations ◽  
Brain Regions ◽  
Major Risk Factor ◽  
Postmortem Brain ◽  
Biological Aging ◽  
Learning Approaches ◽  
Age Related

Abstract Aging is the major risk factor for Alzheimer’s Disease (AD), and as life expectancy increases, neurodegeneration will continue to afflict an ever-increasing proportion of the population. While numerous theories are attempting to explain the drivers behind AD pathology, what unites them is the observation that AD is reliably associated with a progressive buildup of age-related molecular changes. Because of the varying clinical presentations of AD in patients with similar genetic backgrounds, it has been postulated that epigenetics may be implicated in its etiology. Building on our prior work showing that AD pathology is linked to alterations in age-related DNA CpG methylation (DNAme) across various brain regions, we use state-of-the-art machine learning approaches to identify patterns of molecular damage in postmortem brain samples. We show that alterations in DNAme are associated with accelerated biological aging, AD, and the APOE e4 genotype, which is a major risk factor for AD. We also demonstrate that these associations are present in the PFC but not cerebellum -- in line with the current understanding of AD progression in the brain. Finally, we perform whole-exome sequencing and protein mass spectrometry on the same brain samples to test our hypothesis as to whether AD-associated alterations of DNAme are linked with the accumulation of somatic mutations that affect the structural and binding properties of protein epigenetic regulators.

Cultural Variance and Invariance of Age Differences in Social Cognition

2019 ◽  
Author(s):  
Li Chu ◽  
Yang Fang ◽  
Vivian Hiu-Ling Tsang ◽  
Helene H. Fung
Keyword(s):  
Social Cognition ◽  
Cognitive Processing ◽  
Social Cognitive ◽  
Self Regulation ◽  
Cultural Influences ◽  
Biological Aging ◽  
Aging Research ◽  
Age Related ◽  
Norms And Values ◽  
The One

Cognitive processing of social and nonsocial information changes with age. These processes range from the ones that serve “mere” cognitive functions, such as recall strategies and reasoning, to those that serve functions that pertain to self-regulation and relating to others. However, aging and the development of social cognition unfold in different cultural contexts, which may assume distinct social norms and values. Thus, the resulting age-related differences in cognitive and social cognitive processes may differ across cultures. On the one hand, biological aging could render age-related differences in social cognition universal; on the other hand, culture may play a role in shaping some age-related differences. Indeed, many aspects of cognition and social cognition showed different age and culture interactions, and this makes the study of these phenomena more complex. Future aging research on social cognition should take cultural influences into consideration.

scholarly journals BIOMARKER STRATEGIES FOR GEROSCIENCE-GUIDED CLINICAL TRIALS

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S745-S746
Author(s):  
Jamie N Justice ◽  
George A Kuchel ◽  
Nir Barzilai ◽  
Stephen Kritchevsky
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Biological Aging ◽  
Expert Committee ◽  
Biomarkers Of Aging ◽  
Age Related ◽  
Trial Outcomes ◽  
Biology Of Aging ◽  
Potential Use ◽  
Selection Of

Abstract Significant progress in the biology of aging and animal models supports the geroscience hypothesis: by targeting biological aging the onset of age-related diseases can be delayed. Geroscience investigators will test this hypothesis in a multicenter clinical trial, to determine if interventions on biological aging processes can prevent accumulation of multiple age-related diseases and aging phenotypes in older adults. Prodigious activity is underway to develop markers of biological aging, but currently there is no aging biomarker consensus to support geroscience-guided clinical trial outcomes. We convened an expert committee to establish a framework for selection of blood-based biomarkers, emphasizing: feasibility/reliability; aging relevance; ability to predict clinical trial outcomes; and responsiveness to intervention. We applied this framework and identified a short-list of blood-based biomarkers with potential use in multicenter trials on aging. We review progress on efforts to test these candidate biomarkers of aging and development of biomarkers strategy for geroscience-guided clinical trials.

scholarly journals The INSPIRE Bio-resource Research Platform for Healthy Aging and Geroscience: Focus on the Human Translational Research Cohort (The INSPIRE-T Cohort)

2020 ◽  
pp. 1-11 ◽  
Author(s):  
S. Guyonnet ◽  
Y. Rolland ◽  
C. Takeda ◽  
P.-J. Ousset ◽  
I. Ader ◽  
...  
Keyword(s):  
Health Care ◽  
Translational Research ◽  
Healthy Aging ◽  
Care Pathway ◽  
Integrative Approach ◽  
Biological Aging ◽  
Imaging Data ◽  
Aging Research ◽  
Age Related

Background: The Geroscience field focuses on the core biological mechanisms of aging, which are involved in the onset of age-related diseases, as well as declines in intrinsic capacity (IC) (body functions) leading to dependency. A better understanding on how to measure the true age of an individual or biological aging is an essential step that may lead to the definition of putative markers capable of predicting healthy aging. Objectives: The main objective of the INStitute for Prevention healthy agIng and medicine Rejuvenative (INSPIRE) Platform initiative is to build a program for Geroscience and healthy aging research going from animal models to humans and the health care system. The specific aim of the INSPIRE human translational cohort (INSPIRE-T cohort) is to gather clinical, digital and imaging data, and perform relevant and extensive biobanking to allow basic and translational research on humans. Methods: The INSPIRE-T cohort consists in a population study comprising 1000 individuals in Toulouse and surrounding areas (France) of different ages (20 years or over - no upper limit for age) and functional capacity levels (from robustness to frailty, and even dependency) with follow-up over 10 years. Diversified data are collected annually in research facilities or at home according to standardized procedures. Between two annual visits, IC domains are monitored every 4-month by using the ICOPE Monitor app developed in collaboration with WHO. Once IC decline is confirmed, participants will have a clinical assessment and blood sampling to investigate markers of aging at the time IC declines are detected. Biospecimens include blood, urine, saliva, and dental plaque that are collected from all subjects at baseline and then, annually. Nasopharyngeal swabs and cutaneous surface samples are collected in a large subgroup of subjects every two years. Feces, hair bulb and skin biopsy are collected optionally at the baseline visit and will be performed again during the longitudinal follow up. Expected Results: Recruitment started on October 2019 and is expected to last for two years. Bio-resources collected and explored in the INSPIRE-T cohort will be available for academic and industry partners aiming to identify robust (set of) markers of aging, age-related diseases and IC evolution that could be pharmacologically or non-pharmacologically targetable. The INSPIRE-T will also aim to develop an integrative approach to explore the use of innovative technologies and a new, function and person-centered health care pathway that will promote a healthy aging.

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