scholarly journals METABOLIC INTEGRITY – A FACTOR IN AGING AND A PLAYER IN THE MECHANISMS OF CR

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S67-S67
Author(s):  
Rozalyn Anderson
Keyword(s):  
Metabolic Pathways ◽  
Nonhuman Primates ◽  
Disease Risk ◽  
Metabolic Dysfunction ◽  
Aging Research ◽  
Root Cause ◽  
Related Disease ◽  
Metabolic Component ◽  
Age Related ◽  
Metabolic Biomarkers

Abstract An emerging paradigm in aging research identifies metabolic dysfunction as a root cause in age-related disease vulnerability. Several diseases of aging, including diabetes, cancer, and neurodegeneration, have an established metabolic component. Our studies have focused on links between metabolic status and disease vulnerability. Caloric restriction (CR) delays aging and the onset of age-related disease in diverse species, including nonhuman primates. Molecular profiling identifies CR responsive elements in the transcriptome, proteome, and metabolome that are highly enriched for metabolic pathways and in particular mitochondrial processes. These data show that improvements in health and survival are associated with maintenance of system wide metabolic homeostasis and preserved energy metabolism among tissues. Metabolic biomarkers identified in these studies may be clinically relevant for the early identification of elevated disease risk in humans and could even be potential targets for the development of novel strategies to lower disease vulnerability as a function of age.

Calorie Restriction in Nonhuman Primates: Implications for Age-Related Disease Risk

1998 ◽  
Vol 1 (4) ◽  
pp. 315-326 ◽  
Author(s):  
MARK A. LANE ◽  
ANGELA BLACK ◽  
DONALD K. INGRAM ◽  
GEORGE S. ROTH
Keyword(s):  
Calorie Restriction ◽  
Nonhuman Primates ◽  
Disease Risk ◽  
Related Disease ◽  
Age Related

Summary and Assessment of Studies on Cardiac Aging in Nonhuman Primates

2021 ◽  
Author(s):  
Hillary F Huber ◽  
Peter W Nathanielsz ◽  
Geoffrey D Clarke
Keyword(s):  
Life Course ◽  
Early Life ◽  
Nonhuman Primates ◽  
Disease Risk ◽  
Future Research ◽  
Cardiac Aging ◽  
Related Disease ◽  
Biomarkers Of Aging ◽  
Age Related ◽  
Wide Range

Nonhuman primates (NHP) are important translational models for cardiac aging. To assess progress in this research area and to provide a reference for other investigators, we identified papers indexed in PubMed to determine what species, ages, outcomes, treatments, and approaches have been studied. Since 1983, 33 studies of cardiac aging in NHP have been published.Of these, 27 used species of macaque, 6 baboon, 1 vervet, 1 orangutan, and 1 marmoset (some studies were multispecies).Common research approaches were echocardiography, ECG, and histology of the left ventricle. Only 10 studies performedsex-based analyses. The average age of the oldest macaque studied was 26 y. The reported mean lifespan of macaques incaptivity is around 30 y. The age of the oldest baboon studied was 24 y. Baboons in captivity are reported to live on averageto 21 y. Twelve studies took a “life course” approach, studying animals of a wide range of ages from less than or equal to 10y through the late teens to thirties, and employing analyses designed to show change over time. Keeping NHP into old ageis a major challenge for biomedical research. The ideal design is to start monitoring in early life and to track how cardiacstructure and function change with age. Important issues for future research are an increased focus on life-course approaches, investment in existing life-course NHP cohorts, better reporting of study sample characteristics, more molecular studies to identify genetic risk factors and mechanisms, attention to sex as a biological variable, a move away from descriptive reports to mechanistic studies, development of biomarkers to predict disease risk, and exploration of interventions that are implemented early in life to prevent or delay age-related disease later in life. Reducing exposure to early life adversity, identifying early-life biomarkers of aging and age-related disease, and early treatment can contribute to longer health span.

scholarly journals Genome and Epigenome Editing in Mechanistic Studies of Human Aging and Aging-Related Disease

Gerontology ◽  
2016 ◽  
Vol 63 (2) ◽  
pp. 103-117 ◽  
Author(s):  
Cia-Hin Lau ◽  
Yousin Suh
Keyword(s):  
Animal Models ◽  
Genetic Manipulation ◽  
Logic Gate ◽  
Therapeutic Interventions ◽  
Human Aging ◽  
Aging Research ◽  
Epigenome Editing ◽  
Related Disease ◽  
Age Related

The recent advent of genome and epigenome editing technologies has provided a new paradigm in which the landscape of the human genome and epigenome can be precisely manipulated in their native context. Genome and epigenome editing technologies can be applied to many aspects of aging research and offer the potential to develop novel therapeutics against age-related diseases. Here, we discuss the latest technological advances in the CRISPR-based genome and epigenome editing toolbox, and provide insight into how these synthetic biology tools could facilitate aging research by establishing in vitro cell and in vivo animal models to dissect genetic and epigenetic mechanisms underlying aging and age-related diseases. We discuss recent developments in the field with the aims to precisely modulate gene expression and dynamic epigenetic landscapes in a spatial and temporal manner in cellular and animal models, by complementing the CRISPR-based editing capability with conditional genetic manipulation tools including chemically inducible expression systems, optogenetics, logic gate genetic circuits, tissue-specific promoters, and the serotype-specific adeno-associated virus. We also discuss how the combined use of genome and epigenome editing tools permits investigators to uncover novel molecular pathways involved in the pathophysiology and etiology conferred by risk variants associated with aging and aging-related disease. A better understanding of the genetic and epigenetic regulatory mechanisms underlying human aging and age-related disease will significantly contribute to the developments of new therapeutic interventions for extending health span and life span, ultimately improving the quality of life in the elderly populations.

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 OMICS IN AGING RESEARCH: FROM BIOMARKERS TO SYSTEMS BIOLOGY

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S234-S234
Author(s):  
Daniel Promislow
Keyword(s):  
Natural Variation ◽  
Natural Populations ◽  
Network Models ◽  
Explanatory Gap ◽  
Aging Research ◽  
Evolutionary Forces ◽  
Related Disease ◽  
Diverse Species ◽  
Age Related ◽  
Complex Human Traits

Abstract Advances in whole genome sequencing have dramatically increased our potential to understand what shapes variation in rates of aging and age-related disease in natural populations, but we are still far from realizing this potential. Researchers have identified thousands of genetic markers associated with complex human traits. However, these markers typically explain a very small fraction of the observed variance, leaving an enormous explanatory gap between genotype and phenotype. I will present data from diverse species to illustrate the power of so-called endophenotypes—the epigenome, transcriptome, proteome, and metabolome—to bridge the genotype-phenotype gap. Using multivariate and network models that integrate genetic information with other endophenotype variation, we are closer than ever to understanding the mechanisms that account for natural variation in aging and age-related disease, and the evolutionary forces that have shaped that variation.

scholarly journals Flavonoids and age-related disease: Risk, benefits and critical windows

Maturitas ◽  
2010 ◽  
Vol 66 (2) ◽  
pp. 163-171 ◽  
Author(s):  
J.K. Prasain ◽  
S.H. Carlson ◽  
J.M. Wyss
Keyword(s):  
Disease Risk ◽  
Related Disease ◽  
Age Related

scholarly journals Physical Activity and Telomere Biology: Exploring the Link with Aging-Related Disease Prevention

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Andrew T. Ludlow ◽  
Stephen M. Roth
Keyword(s):  
Physical Activity ◽  
Physical Inactivity ◽  
Replicative Senescence ◽  
Disease Risk ◽  
Future Research ◽  
Activity Levels ◽  
Related Disease ◽  
Age Related ◽  
A Cell ◽  
Telomere Biology

Physical activity is associated with reduced risk of several age-related diseases as well as with increased longevity in both rodents and humans. Though these associations are well established, evidence of the molecular and cellular factors associated with reduced disease risk and increased longevity resulting from physical activity is sparse. A long-standing hypothesis of aging is the telomere hypothesis: as a cell divides, telomeres shorten resulting eventually in replicative senescence and an aged phenotype. Several reports have recently associated telomeres and telomere-related proteins to diseases associated with physical inactivity and aging including cardiovascular disease, insulin resistance, and hypertension. Interestingly several reports have also shown that longer telomeres are associated with higher physical activity levels, indicating a potential mechanistic link between physical activity, reduced age-related disease risk, and longevity. The primary purpose of this review is to discuss the potential importance of physical activity in telomere biology in the context of inactivity- and age-related diseases. A secondary purpose is to explore potential mechanisms and important avenues for future research in the field of telomeres and diseases associated with physical inactivity and aging.

scholarly journals Aging-Related Metabolic Dysfunction in the Salivary Gland: A Review of the Literature

2021 ◽  
Vol 22 (11) ◽  
pp. 5835
Author(s):  
Nguyen Khanh Toan ◽  
Sang-Gun Ahn
Keyword(s):  
Salivary Gland ◽  
Metabolic Pathways ◽  
Metabolic Dysfunction ◽  
Review Of The Literature ◽  
Comprehensive Overview ◽  
Salivary Gland Dysfunction ◽  
Age Related ◽  
Oral Physiology ◽  
Saliva Flow ◽  
Choice Of Therapy

Aging-related salivary dysfunction commonly induces the poor oral health, including decreased saliva flow and dental caries. Although the clinical significance of the salivary glands is well-known, the complex metabolic pathways contributing to the aging-dysfunction process are only beginning to be uncovered. Here, we provide a comprehensive overview of the metabolic changes in aging-mediated salivary gland dysfunction as a key aspect of oral physiology. Several metabolic neuropeptides or hormones are involved in causing or contributing to salivary gland dysfunction, including hyposalivation and age-related diseases. Thus, aging-related metabolism holds promise for early diagnosis, increased choice of therapy and the identification of new metabolic pathways that could potentially be targeted in salivary gland dysfunction.

scholarly journals Deregulation of CRTCs in Aging and Age-Related Disease Risk

2017 ◽  
Vol 33 (5) ◽  
pp. 303-321 ◽  
Author(s):  
Caroline C. Escoubas ◽  
Carlos G. Silva-García ◽  
William B. Mair
Keyword(s):  
Disease Risk ◽  
Related Disease ◽  
Age Related

scholarly journals Human genetic analyses of organelles highlight the nucleus in age-related trait heritability

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Rahul Gupta ◽  
Konrad Karczewski ◽  
Daniel Howrigan ◽  
Benjamin Neale ◽  
Vamsi Mootha, MD
Keyword(s):  
Transcription Factors ◽  
Disease Risk ◽  
Purifying Selection ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Mitochondrial Proteome ◽  
Related Disease ◽  
Age Related ◽  
Genes Encoding ◽  
Open Question ◽  
Related Trait

Most age-related human diseases are accompanied by a decline in cellular organelle integrity, including impaired lysosomal proteostasis and defective mitochondrial oxidative phosphorylation. An open question, however, is the degree to which inherited variation in or near genes encoding each organelle contributes to age-related disease pathogenesis. Here, we evaluate if genetic loci encoding organelle proteomes confer greater-than-expected age-related disease risk. As mitochondrial dysfunction is a 'hallmark' of aging, we begin by assessing nuclear and mitochondrial DNA loci near genes encoding the mitochondrial proteome and surprisingly observe a lack of enrichment across 24 age-related traits. Within nine other organelles, we find no enrichment with one exception: the nucleus, where enrichment emanates from nuclear transcription factors. In agreement, we find that genes encoding several organelles tend to be 'haplosufficient', while we observe strong purifying selection against heterozygous protein-truncating variants impacting the nucleus. Our work identifies common variation near transcription factors as having outsize influence on age-related trait risk, motivating future efforts to determine if and how this inherited variation then contributes to observed age-related organelle deterioration.

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