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Cell Jan 2023Aging is driven by hallmarks fulfilling the following three premises: (1) their age-associated manifestation, (2) the acceleration of aging by experimentally... (Review)
Review
Aging is driven by hallmarks fulfilling the following three premises: (1) their age-associated manifestation, (2) the acceleration of aging by experimentally accentuating them, and (3) the opportunity to decelerate, stop, or reverse aging by therapeutic interventions on them. We propose the following twelve hallmarks of aging: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. These hallmarks are interconnected among each other, as well as to the recently proposed hallmarks of health, which include organizational features of spatial compartmentalization, maintenance of homeostasis, and adequate responses to stress.
Topics: Cellular Senescence; Epigenesis, Genetic; Proteostasis; Stem Cells; Aging
PubMed: 36599349
DOI: 10.1016/j.cell.2022.11.001 -
Annals of Agricultural and... 2014The aging of humans is a physiological and dynamic process ongoing with time. In accordance with most gerontologists' assertions it starts in the fourth decade of life... (Review)
Review
The aging of humans is a physiological and dynamic process ongoing with time. In accordance with most gerontologists' assertions it starts in the fourth decade of life and leads to death. The process of human aging is complex and individualized, occurs in the biological, psychological and social sphere. Biological aging is characterized by progressive age-changes in metabolism and physicochemical properties of cells, leading to impaired self-regulation, regeneration, and to structural changes and functional tissues and organs. It is a natural and irreversible process which can run as successful aging, typical or pathological. Biological changes that occur with age in the human body affect mood, attitude to the environment, physical condition and social activity, and designate the place of seniors in the family and society. Psychical ageing refers to human awareness and his adaptability to the ageing process. Among adaptation attitudes we can differentiate: constructive, dependence, hostile towards others and towards self attitudes. With progressed age, difficulties with adjustment to the new situation are increasing, adverse changes in the cognitive and intellectual sphere take place, perception process involutes, perceived sensations and information received is lowered, and thinking processes change. Social ageing is limited to the role of an old person is culturally conditioned and may change as customs change. Social ageing refers to how a human being perceives the ageing process and how society sees it.
Topics: Adaptation, Psychological; Aging; Humans; Motor Activity; Sociological Factors
PubMed: 25528930
DOI: 10.5604/12321966.1129943 -
Biomarkers in Medicine 2014Biomarkers and Ageing 25 February 2014, London, UK This conference was organized by Euroscicon and was part of the 2014 Ageing Summit. The central theme was biomarkers...
Biomarkers and Ageing 25 February 2014, London, UK This conference was organized by Euroscicon and was part of the 2014 Ageing Summit. The central theme was biomarkers and aging including current research on biomarkers at the genomics and proteomics level. The informal atmosphere of the conference promoted interaction and networking opportunities between key leaders from industry, academic and clinics. Presentations as well as the discussion panel session brought opportunities to widely discuss the relevance of biomarkers as signatures for human aging or age-related diseases. The meeting highlighted the importance of genomics and regulatory elements in aging, their probable role in successful aging and their potential interest for future antiaging approaches. The meeting was chaired by David Melzer and Lorna Harries (University of Exeter, UK).
Topics: Aging; Biomarkers; Bone and Bones; Humans; Molecular Imaging; RNA Splicing; Reference Values; Skin Aging; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 25123029
DOI: 10.2217/bmm.14.40 -
Medicine, Health Care, and Philosophy May 2015In this paper, I will argue that ageing can be construed as disease. First, the concept of disease is discussed, where the distinction is made between two lines of...
In this paper, I will argue that ageing can be construed as disease. First, the concept of disease is discussed, where the distinction is made between two lines of thought, an objectivist and a subjectivist one. After determining the disease conception to be used throughout the argument, it is proposed that senescence could be seen as disease. Three common counterarguments are discussed, none of which appears strong enough to effectively counter the advocated view. In the third section, two potential implications of the view advocated here will be briefly touched upon. These are the quest for a cure or treatment for ageing and the general attitude towards the elderly. It is concluded that, utilizing an objective disease concept, ageing could be seen as a disease. None of the considered counterarguments packs enough of a punch to discard this. The implications are complex and intertwined, but need not be negative.
Topics: Adaptation, Psychological; Aging; Disease; Humans; Medicalization; Philosophy, Medical
PubMed: 25240472
DOI: 10.1007/s11019-014-9600-y -
Mechanisms of Ageing and Development Jul 2020The disease criteria used by the World Health Organization (WHO) were applied to human biological aging in order to assess whether aging can be classified as a disease.... (Review)
Review
The disease criteria used by the World Health Organization (WHO) were applied to human biological aging in order to assess whether aging can be classified as a disease. These criteria were developed for the 11th revision of the International Classification of Diseases (ICD) and included disease diagnostics, mechanisms, course and outcomes, known interventions, and linkage to genetic and environmental factors. RESULTS: Biological aging can be diagnosed with frailty indices, functional, blood-based biomarkers. A number of major causal mechanisms of human aging involved in various organs have been described, such as inflammation, replicative cellular senescence, immune senescence, proteostasis failures, mitochondrial dysfunctions, fibrotic propensity, hormonal aging, body composition changes, etc. We identified a number of clinically proven interventions, as well as genetic and environmental factors of aging. Therefore, aging fits the ICD-11 criteria and can be considered a disease. Our proposal was submitted to the ICD-11 Joint Task force, and this led to the inclusion of the extension code for "Ageing-related" (XT9T) into the "Causality" section of the ICD-11. This might lead to greater focus on biological aging in global health policy and might provide for more opportunities for the new therapy developers.
Topics: Age Factors; Aging; Dietary Supplements; Health Status; Healthy Lifestyle; Humans; International Classification of Diseases; Risk Reduction Behavior; Terminology as Topic
PubMed: 32251691
DOI: 10.1016/j.mad.2020.111230 -
Trends in Cell Biology Jun 2018Cellular senescence is a permanent state of cell cycle arrest that promotes tissue remodeling during development and after injury, but can also contribute to the decline... (Review)
Review
Cellular senescence is a permanent state of cell cycle arrest that promotes tissue remodeling during development and after injury, but can also contribute to the decline of the regenerative potential and function of tissues, to inflammation, and to tumorigenesis in aged organisms. Therefore, the identification, characterization, and pharmacological elimination of senescent cells have gained attention in the field of aging research. However, the nonspecificity of current senescence markers and the existence of different senescence programs strongly limit these tasks. Here, we describe the molecular regulators of senescence phenotypes and how they are used for identifying senescent cells in vitro and in vivo. We also highlight the importance that these levels of regulations have in the development of therapeutic targets.
Topics: Aging; Biomarkers; Cellular Senescence; DNA Damage; Genetic Markers; Humans; Phenotype
PubMed: 29477613
DOI: 10.1016/j.tcb.2018.02.001 -
Nature Jul 2019For several decades, understanding ageing and the processes that limit lifespan have challenged biologists. Thirty years ago, the biology of ageing gained unprecedented... (Review)
Review
For several decades, understanding ageing and the processes that limit lifespan have challenged biologists. Thirty years ago, the biology of ageing gained unprecedented scientific credibility through the identification of gene variants that extend the lifespan of multicellular model organisms. Here we summarize the milestones that mark this scientific triumph, discuss different ageing pathways and processes, and suggest that ageing research is entering a new era that has unique medical, commercial and societal implications. We argue that this era marks an inflection point, not only in ageing research but also for all biological research that affects the human healthspan.
Topics: Aging; Biomedical Research; Circadian Clocks; Clinical Trials as Topic; Healthy Aging; Humans; Inflammation; Longevity; Mitochondria; Nutritional Status; Oxidative Stress; Rejuvenation; Signal Transduction
PubMed: 31292558
DOI: 10.1038/s41586-019-1365-2 -
Nature Reviews. Neurology Oct 2019Ageing is the primary risk factor for most neurodegenerative diseases, including Alzheimer disease (AD) and Parkinson disease (PD). One in ten individuals aged ≥65... (Review)
Review
Ageing is the primary risk factor for most neurodegenerative diseases, including Alzheimer disease (AD) and Parkinson disease (PD). One in ten individuals aged ≥65 years has AD and its prevalence continues to increase with increasing age. Few or no effective treatments are available for ageing-related neurodegenerative diseases, which tend to progress in an irreversible manner and are associated with large socioeconomic and personal costs. This Review discusses the pathogenesis of AD, PD and other neurodegenerative diseases, and describes their associations with the nine biological hallmarks of ageing: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, mitochondrial dysfunction, cellular senescence, deregulated nutrient sensing, stem cell exhaustion and altered intercellular communication. The central biological mechanisms of ageing and their potential as targets of novel therapies for neurodegenerative diseases are also discussed, with potential therapies including NAD precursors, mitophagy inducers and inhibitors of cellular senescence.
Topics: Aging; Brain; DNA Damage; Epigenesis, Genetic; Humans; Mitophagy; Neurodegenerative Diseases; Risk Factors
PubMed: 31501588
DOI: 10.1038/s41582-019-0244-7 -
Nature Nov 2016Although systemic diseases take the biggest toll on human health and well-being, increasingly, a failing brain is the arbiter of a death preceded by a gradual loss of... (Review)
Review
Although systemic diseases take the biggest toll on human health and well-being, increasingly, a failing brain is the arbiter of a death preceded by a gradual loss of the essence of being. Ageing, which is fundamental to neurodegeneration and dementia, affects every organ in the body and seems to be encoded partly in a blood-based signature. Indeed, factors in the circulation have been shown to modulate ageing and to rejuvenate numerous organs, including the brain. The discovery of such factors, the identification of their origins and a deeper understanding of their functions is ushering in a new era in ageing and dementia research.
Topics: Aging; Animals; Brain; Cell Communication; Humans; Inflammation; Neurodegenerative Diseases; Proteome; Rejuvenation
PubMed: 27830812
DOI: 10.1038/nature20411 -
Nature Cell Biology Feb 2022Ageing organisms accumulate senescent cells that are thought to contribute to body dysfunction. Telomere shortening and damage are recognized causes of cellular... (Review)
Review
Ageing organisms accumulate senescent cells that are thought to contribute to body dysfunction. Telomere shortening and damage are recognized causes of cellular senescence and ageing. Several human conditions associated with normal ageing are precipitated by accelerated telomere dysfunction. Here, we systematize a large body of evidence and propose a coherent perspective to recognize the broad contribution of telomeric dysfunction to human pathologies.
Topics: Age Factors; Aging; Animals; Cellular Senescence; DNA Damage; Humans; Noncommunicable Diseases; Telomere; Telomere Homeostasis; Telomere Shortening
PubMed: 35165420
DOI: 10.1038/s41556-022-00842-x