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Ageing Research Reviews Jan 2024Cellular senescence is a state of terminal cell cycle arrest associated with various macromolecular changes and a hypersecretory phenotype. In the brain, senescent cells... (Review)
Review
Cellular senescence is a state of terminal cell cycle arrest associated with various macromolecular changes and a hypersecretory phenotype. In the brain, senescent cells naturally accumulate during aging and at sites of age-related pathologies. Here, we discuss the recent advances in understanding the accumulation of senescent cells in brain aging and disorders. Here we highlight the phenotypical heterogeneity of different senescent brain cell types, highlighting the potential importance of subtype-specific features for physiology and pathology. We provide a comprehensive overview of various senescent cell types in naturally occurring aging and the most common neurodegenerative disorders. Finally, we critically discuss the potential of adapting senotherapeutics to improve brain health and reduce pathological progression, addressing limitations and future directions for application and development.
Topics: Humans; Aging; Cellular Senescence; Brain; Neurodegenerative Diseases; Cell Cycle Checkpoints
PubMed: 38030088
DOI: 10.1016/j.arr.2023.102141 -
Clinics and Research in Hepatology and... Feb 2020The aging of the population, the increased prevalence of chronic liver diseases in elderly and the need to broaden the list of potential liver donors enjoin us to better... (Review)
Review
The aging of the population, the increased prevalence of chronic liver diseases in elderly and the need to broaden the list of potential liver donors enjoin us to better understand what is an aged liver. In this review, we provide a brief introduction to cellular senescence, revisit the main morphological and functional modifications of the liver induced by aging, particularly concerning metabolism, immune response and regeneration, and try to elude some of the signalling pathways responsible for these modifications. Finally, we discuss the clinical consequences of aging on chronic liver diseases and the implications of older age for donors and recipients in liver transplantation.
Topics: Aged; Aging; Cellular Senescence; Homeostasis; Humans; Liver; Liver Diseases
PubMed: 31427197
DOI: 10.1016/j.clinre.2019.07.011 -
Mechanisms of Ageing and Development Jul 2020The functional decline that is observed in HSCs upon aging is attributed mainly to cell intrinsic factors that regulate quiescence, self-renewal and differentiation.... (Review)
Review
The functional decline that is observed in HSCs upon aging is attributed mainly to cell intrinsic factors that regulate quiescence, self-renewal and differentiation. MicroRNAs (miRs) have an indispensable role in the regulation of HSCs and have been shown to also regulate processes related to tissue aging in specific cell types. Here we discuss the role of miRs in the regulation of HSC self-renewal and differentiation throughout life and its implications for future research.
Topics: Aging; Animals; Cell Differentiation; Cellular Senescence; Hematopoietic Stem Cells; Humans; MicroRNAs
PubMed: 32512019
DOI: 10.1016/j.mad.2020.111281 -
Science (New York, N.Y.) Jun 2024Long associated with aging, senescent cells can promote health and have physiological roles. (Review)
Review
Long associated with aging, senescent cells can promote health and have physiological roles.
Topics: Animals; Humans; Aging; Cellular Senescence; Mice; Notophthalmus viridescens; Senotherapeutics; Drug Development
PubMed: 38900869
DOI: 10.1126/science.adj7050 -
Neuroscience and Biobehavioral Reviews Dec 2023Ageing is associated with profound changes in behaviour that could influence exposure and susceptibility to infectious disease. As well as determining emergent patterns... (Review)
Review
Ageing is associated with profound changes in behaviour that could influence exposure and susceptibility to infectious disease. As well as determining emergent patterns of infection across individuals of different ages, behavioural ageing could interact with, confound, or counteract age-related changes in other traits. Here, we examine how behavioural ageing can manifest and influence patterns of infection in wild animals. We discuss a range of age-related changes that involve interactions between behaviour and components of exposure and susceptibility to infection, including social ageing and immunosenescence, acquisition of novel parasites and pathogens with age, changes in spatial behaviours, and age-related hygiene and sickness behaviours. Overall, most behavioural changes are expected to result in a reduced exposure rate, but there is relatively little evidence for this phenomenon, emerging largely from a rarity of explicit tests of exposure changes over the lifespan. This review offers a framework for understanding how ageing, behaviour, immunity, and infection interact, providing a series of hypotheses and testable predictions to improve our understanding of health in ageing societies.
Topics: Humans; Animals; Aging; Longevity; Communicable Diseases
PubMed: 37839673
DOI: 10.1016/j.neubiorev.2023.105426 -
Nature Feb 2022The Dog Aging Project is a long-term longitudinal study of ageing in tens of thousands of companion dogs. The domestic dog is among the most variable mammal species in...
The Dog Aging Project is a long-term longitudinal study of ageing in tens of thousands of companion dogs. The domestic dog is among the most variable mammal species in terms of morphology, behaviour, risk of age-related disease and life expectancy. Given that dogs share the human environment and have a sophisticated healthcare system but are much shorter-lived than people, they offer a unique opportunity to identify the genetic, environmental and lifestyle factors associated with healthy lifespan. To take advantage of this opportunity, the Dog Aging Project will collect extensive survey data, environmental information, electronic veterinary medical records, genome-wide sequence information, clinicopathology and molecular phenotypes derived from blood cells, plasma and faecal samples. Here, we describe the specific goals and design of the Dog Aging Project and discuss the potential for this open-data, community science study to greatly enhance understanding of ageing in a genetically variable, socially relevant species living in a complex environment.
Topics: Aging; Animals; Biomarkers; Built Environment; Clinical Trials, Veterinary as Topic; Cross-Sectional Studies; Data Collection; Dogs; Female; Frailty; Gene-Environment Interaction; Genome-Wide Association Study; Goals; Healthy Aging; Humans; Inflammation; Information Dissemination; Informed Consent; Life Style; Longevity; Longitudinal Studies; Male; Models, Animal; Multimorbidity; Pets; Privacy; Sirolimus
PubMed: 35110758
DOI: 10.1038/s41586-021-04282-9 -
Biochemistry. Biokhimiia Dec 2022As recently as in 2002 gerontologists widely thought that an aging program that purposely caused aging in mammals was impossible and therefore scientifically ridiculous... (Review)
Review
As recently as in 2002 gerontologists widely thought that an aging program that purposely caused aging in mammals was impossible and therefore scientifically ridiculous because it violated widely accepted concepts regarding the nature of the evolution process. However, a number of modern evolutionary mechanics concepts such as group selection and evolvability suggest that an individually adverse trait like aging can evolve if it creates an advantage (reduced probability of extinction) for a population. Genetics discoveries suggest that aging creates multiple population advantages and, therefore, aging programs that purposely cause and regulate aging evolved in mammals. This led to various concepts regarding the nature of the program. One such concept is that aging is a completely genetically specified function of age, essentially a biological clock. However, this article presents evidence and theoretical basis for the idea that the programmed aging function is controlled by an adaptive mechanism that can sense local or temporary conditions that affect the optimum aging function and adjust it to compensate for those conditions. This issue is important for medical research because the sensing mechanisms and associated signaling provide additional points at which intervention in the aging process and associated highly age-related diseases could be attempted.
Topics: Animals; Biological Evolution; Aging; Phenotype; Mammals; Biological Clocks
PubMed: 36717437
DOI: 10.1134/S000629792212001X -
Open Biology Nov 2019Ageing appears to be a nearly universal feature of life, ranging from unicellular microorganisms to humans. Longevity depends on the maintenance of cellular... (Review)
Review
Ageing appears to be a nearly universal feature of life, ranging from unicellular microorganisms to humans. Longevity depends on the maintenance of cellular functionality, and an organism's ability to respond to stress has been linked to functional maintenance and longevity. Stress response pathways might indeed become therapeutic targets of therapies aimed at extending the healthy lifespan. Various progeroid syndromes have been linked to genome instability, indicating an important causal role of DNA damage accumulation in the ageing process and the development of age-related pathologies. Recently, non-cell-autonomous mechanisms including the systemic consequences of cellular senescence have been implicated in regulating organismal ageing. We discuss here the role of cellular and systemic mechanisms of ageing and their role in ageing-associated diseases.
Topics: Aging; Animals; Cellular Senescence; DNA Damage; DNA Repair; Genomic Instability; Humans; Longevity; Stress, Physiological
PubMed: 31744423
DOI: 10.1098/rsob.190168 -
Mechanisms of Ageing and Development Sep 2019Aging refers to the progressive deterioration of tissue and organ function over time. Increasing evidence points to the accumulation of highly damaged cell... (Review)
Review
Aging refers to the progressive deterioration of tissue and organ function over time. Increasing evidence points to the accumulation of highly damaged cell cycle-arrested cells with age (cellular senescence) as major reason for the development of certain aging-associated diseases. Recent studies have independently shown that aneuploidy, an abnormal chromosome set, occurs in senescent cells, and that the accumulation of cytoplasmic DNA driven by faulty chromosome segregation during mitosis aids in the establishment of senescence and its associated secretory phenotype known as SASP. Here we review the emerging link between chromosomal instability (CIN) and senescence in the context of aging, with emphasis on the cGAS-STING pathway activation and its role in the development of the SASP. Based on current evidence, we propose that age-associated CIN in mitotically active cells contributes to aging and its associated diseases, and we discuss the inhibition of CIN as a potential strategy to prevent the generation of aneuploid senescent cells and thereby to delay aging.
Topics: Aging; Aneuploidy; Cellular Senescence; Chromosomal Instability; Chromosomes, Human; Humans; Inflammation; Membrane Proteins; Nucleotidyltransferases; Signal Transduction
PubMed: 31102604
DOI: 10.1016/j.mad.2019.111118 -
Ageing Research Reviews Dec 2023Vascular ageing, characterized by structural and functional changes in blood vessels of which arterial stiffness and endothelial dysfunction are key components, is... (Review)
Review
Vascular ageing, characterized by structural and functional changes in blood vessels of which arterial stiffness and endothelial dysfunction are key components, is associated with increased risk of cardiovascular and other age-related diseases. As the global population continues to age, understanding the underlying mechanisms and developing effective therapeutic interventions to mitigate vascular ageing becomes crucial for improving cardiovascular health outcomes. Therefore, this review provides an overview of the current knowledge on pharmacological modulation of vascular ageing, highlighting key strategies and promising therapeutic targets. Several molecular pathways have been identified as central players in vascular ageing, including oxidative stress and inflammation, the renin-angiotensin-aldosterone system, cellular senescence, macroautophagy, extracellular matrix remodelling, calcification, and gasotransmitter-related signalling. Pharmacological and dietary interventions targeting these pathways have shown potential in ameliorating age-related vascular changes. Nevertheless, the development and application of drugs targeting vascular ageing is complicated by various inherent challenges and limitations, such as certain preclinical methodological considerations, interactions with exercise training and sex/gender-related differences, which should be taken into account. Overall, pharmacological modulation of endothelial dysfunction and arterial stiffness as hallmarks of vascular ageing, holds great promise for improving cardiovascular health in the ageing population. Nonetheless, further research is needed to fully elucidate the underlying mechanisms and optimize the efficacy and safety of these interventions for clinical translation.
Topics: Humans; Aging; Oxidative Stress; Cellular Senescence; Vascular Stiffness; Signal Transduction
PubMed: 37956927
DOI: 10.1016/j.arr.2023.102122