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 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 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 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 Aging: What We Can Learn From Elephants

2021 ◽  
Vol 2 ◽  
Author(s):  
Daniella E. Chusyd ◽  
Nicole L. Ackermans ◽  
Steven N. Austad ◽  
Patrick R. Hof ◽  
Michelle M. Mielke ◽  
...  
Keyword(s):  
Cellular Response ◽  
P53 Protein ◽  
Single Copy ◽  
Suppressor Gene ◽  
Brain Anatomy ◽  
Ecological Knowledge ◽  
Aging Research ◽  
Age Related ◽  
Multiple Copies ◽  
Extended Longevity

Elephants are large-brained, social mammals with a long lifespan. Studies of elephants can provide insight into the aging process, which may be relevant to understanding diseases that affect elderly humans because of their shared characteristics that have arisen through independent evolution. Elephants become sexually mature at 12 to 14 years of age and are known to live into, and past, their 7th decade of life. Because of their relatively long lifespans, elephants may have evolved mechanisms to counter age-associated morbidities, such as cancer and cognitive decline. Elephants rely heavily on their memory, and engage in multiple levels of competitive and collaborative relationships because they live in a fission-fusion system. Female matrilineal relatives and dependent offspring form tight family units led by an older-aged matriarch, who serves as the primary repository for social and ecological knowledge in the herd. Similar to humans, elephants demonstrate a dependence on social bonds, memory, and cognition to navigate their environment, behaviors that might be associated with specializations of brain anatomy. Compared with other mammals, the elephant hippocampus is proportionally smaller, whereas the temporal lobe is disproportionately large and expands laterally. The elephant cerebellum is also relatively enlarged, and the cerebral cortex is highly convoluted with numerous gyral folds, more than in humans. Last, an interesting characteristic unique to elephants is the presence of at least 20 copies of the TP53 tumor suppressor gene. Humans have only a single copy. TP53 encodes for the p53 protein, which is known to orchestrate cellular response to DNA damage. The effects of these multiple copies of TP53 are still being investigated, but it may be to protect elephants against multiple age-related diseases. For these reasons, among others, studies of elephants would be highly informative for aging research. Elephants present an underappreciated opportunity to explore further common principles of aging in a large-brained mammal with extended longevity. Such research can contribute to contextualizing our knowledge of age-associated morbidities in humans.

Awareness of Aging Processes

2018 ◽  
Author(s):  
Anne Josephine Dutt ◽  
Hans-Werner Wahl ◽  
Manfred Diehl
Keyword(s):  
Aging Process ◽  
Empirical Work ◽  
Well Being ◽  
Subjective Well Being ◽  
Subjective Age ◽  
Aging Research ◽  
Psychological Variables ◽  
Age Related ◽  
Promising Area ◽  
Age Attitudes

The term Awareness of Aging (AoA) incorporates all aspects of individuals’ perceptions, behavioral experiences, and subjective interpretations related to their process of growing older. In this regard, AoA goes beyond objective descriptions of the aging process, such as calendar age or biological age. Commonly used AoA constructs referring to the ongoing experience of the aging process encompass concepts such as subjective age, attitudes toward one’s own aging, self-perceptions of aging, and awareness of age-related change. AoA also incorporates elements that are more pre-conscious in nature, such as age stereotypes and culturally held notions about the aging process. Despite their theoretically broad common foundation, AoA constructs differ according to their specific frames of reference, such as whether and how they take into account the multidimensionality and multi-directionality of development. Examining the existing body of empirical work identifies several antecedents of AoA, such as sociodemographic “background” variables, physical health and physical functioning, cognition, psychological well-being and mental health, psychological variables (e.g., personality, anxiety), and life events. In general, more positive manifestations on these variables are accompanied by a more positive perception and evaluation of the aging process. Moreover, AoA is longitudinally linked to important developmental outcomes, such as health, cognition, subjective well-being, and mortality. Overall, the study of AoA has developed as a promising area of psychological aging research that has grown in its conceptual and empirical rigor during recent years.

scholarly journals Insights into the Conserved Regulatory Mechanisms of Human and Yeast Aging

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 882 ◽  
Author(s):  
Rashmi Dahiya ◽  
Taj Mohammad ◽  
Mohamed F. Alajmi ◽  
Md. Tabish Rehman ◽  
Gulam Mustafa Hasan ◽  
...  
Keyword(s):  
Aging Process ◽  
Molecular Mechanisms ◽  
Model Organism ◽  
Cellular Functions ◽  
Aging Research ◽  
Yeast Saccharomyces Cerevisiae ◽  
Age Related ◽  
Evolutionarily Conserved ◽  
Yeast Aging ◽  
Key Pathways

Aging represents a significant biological process having strong associations with cancer, diabetes, and neurodegenerative and cardiovascular disorders, which leads to progressive loss of cellular functions and viability. Astonishingly, age-related disorders share several genetic and molecular mechanisms with the normal aging process. Over the last three decades, budding yeast Saccharomyces cerevisiae has emerged as a powerful yet simple model organism for aging research. Genetic approaches using yeast RLS have led to the identification of hundreds of genes impacting lifespan in higher eukaryotes. Numerous interventions to extend yeast lifespan showed an analogous outcome in multi-cellular eukaryotes like fruit flies, nematodes, rodents, and humans. We collected and analyzed a multitude of observations from published literature and provide the contribution of yeast in the understanding of aging hallmarks most applicable to humans. Here, we discuss key pathways and molecular mechanisms that underpin the evolutionarily conserved aging process and summarize the current understanding and clinical applicability of its trajectories. Gathering critical information on aging biology would pave the way for future investigation targeted at the discovery of aging interventions.

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.

scholarly journals Natural extract and its fractions isolated from the marine bacterium Pseudoalteromonas flavipulchra STILL-33 have antioxidant and antiaging activities in Schizosaccharomyces pombe

2020 ◽  
Vol 20 (3) ◽  
Author(s):  
Muhammad Eka Prastya ◽  
Rika Indri Astuti ◽  
Irmanida Batubara ◽  
Hiroshi Takagi ◽  
Aris Tri Wahyudi
Keyword(s):  
Schizosaccharomyces Pombe ◽  
Fission Yeast ◽  
Aging Process ◽  
Marine Bacterium ◽  
Mitochondrial Activity ◽  
Oxygen Species ◽  
Related Disease ◽  
Age Related

ABSTRACT Investigations into the potential for pharmacological inhibition of the aging process and the onset of age-related disease are increasingly garnering attention. Here, we analyzed the antiaging properties of natural compounds derived from several marine bacteria in vitro and in vivo using the fission yeast Schizosaccharomyces pombe. The Pseudoalteromonas flavipulchra STILL-33 extract exhibited high antioxidant and antiglycation activities in vitro. We then characterized two antioxidant active fractions isolated from this extract. In addition, we showed that the P. flavipulchra STILL-33 extract or either of its two active fractions (Fractions 1 and 2) could extend the longevity of fission yeast. Moreover, the particular extract and two active fractions were found to induce mitochondrial activity and to delay the G1 phase of the fission yeast cell cycle, perhaps by improving the aging process. The P. flavipulchra STILL-33 extract and Fraction 1 also increased the expression of the catalase-encoding ctt1+ gene and thereby decreased the reactive oxygen species level. Structural analysis showed that Fraction 1 was dominated by l-arginine and ipriflavone, and we showed indeed that the two corresponding commercial products increase the fission yeast lifespan. As for Fraction 2 was identified as the putative structure of butamben. Together, these results should facilitate the discovery of additional antiaging compounds from P. flavipulchra and ultimately the development of novel antiaging compounds for pharmaceutical use.

scholarly journals Repressed Wnt Signaling Accelerates the Aging Process in Mouse Eyes

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Yujin Zhang ◽  
Joseph Jeffrey ◽  
Fei Dong ◽  
Jianhua Zhang ◽  
Winston W.-Y. Kao ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Cellular Response ◽  
Aging Process ◽  
Functional Decline ◽  
Corneal Stroma ◽  
Accelerated Aging ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Anterior Lens Capsule

Purpose. Ocular aging is a natural process of functional decline in vision. When the process reaches a point that compromised vision affects normal daily activity, it manifests as age-related ocular diseases, such as age-related macular degeneration, cataracts, glaucoma, and pseudoexfoliation syndrome. We previously reported that repressed Wnt signaling accelerated the maturation of corneal epithelium during tissue development. Here, we explore the hypothesis that repressed Wnt signaling is associated with accelerated aging in mouse eyes. Methods. Wnt ligand antagonist secreted frizzled-related protein 1 (sFRP1) was expressed in the corneal stroma by a tissue-specific, inducible, bitransgenic system. Tissue structure was analyzed for signs of aging. Signal transduction analysis was performed to determine the cellular response to sFRP1. Results. Mouse eyes with sFRP1 expression showed signs of accelerated aging, resembling those found in pseudoexfoliation (PEX) syndrome, a known age-related disease. Specific findings include granular deposition on the surface of the anterior lens capsule, pigment loss from the anterior surface of the iris, the presence of fibrillary material in the anterior chamber, and changes in cell size (polymegethism) and shape (pleomorphism) of the corneal endothelial cells. In vitro studies demonstrated that sFRP1 did not inhibit Wnt5a function and that cells responded to sFRP1 and Wnt5a in a very similar manner. Conclusion. The expression of sFRP1 accelerates the aging process in mouse eyes and future studies are warranted to elucidate the underlying mechanisms.

scholarly journals ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases

2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
Pierpaola Davalli ◽  
Tijana Mitic ◽  
Andrea Caporali ◽  
Angela Lauriola ◽  
Domenico D’Arca
Keyword(s):  
Aging Process ◽  
Molecular Mechanisms ◽  
Cell Senescence ◽  
Therapeutic Interventions ◽  
Causal Connection ◽  
Oxygen Species ◽  
The Novel ◽  
Age Related ◽  
Multiple Levels ◽  
Stress Damage

The aging process worsens the human body functions at multiple levels, thus causing its gradual decrease to resist stress, damage, and disease. Besides changes in gene expression and metabolic control, the aging rate has been associated with the production of high levels of Reactive Oxygen Species (ROS) and/or Reactive Nitrosative Species (RNS). Specific increases of ROS level have been demonstrated as potentially critical for induction and maintenance of cell senescence process. Causal connection between ROS, aging, age-related pathologies, and cell senescence is studied intensely. Senescent cells have been proposed as a target for interventions to delay the aging and its related diseases or to improve the diseases treatment. Therapeutic interventions towards senescent cells might allow restoring the health and curing the diseases that share basal processes, rather than curing each disease in separate and symptomatic way. Here, we review observations on ROS ability of inducing cell senescence through novel mechanisms that underpin aging processes. Particular emphasis is addressed to the novel mechanisms of ROS involvement in epigenetic regulation of cell senescence and aging, with the aim to individuate specific pathways, which might promote healthy lifespan and improve aging.

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