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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 -
Sub-cellular Biochemistry 2019Ageing is defined by the loss of functional reserve over time, leading to a decreased tissue homeostasis and increased age-related pathology. The accumulation of damage... (Review)
Review
Ageing is defined by the loss of functional reserve over time, leading to a decreased tissue homeostasis and increased age-related pathology. The accumulation of damage including DNA damage contributes to driving cell signaling pathways that, in turn, can drive different cell fates, including senescence and apoptosis, as well as mitochondrial dysfunction and inflammation. In addition, the accumulation of cell autonomous damage with time also drives ageing through non-cell autonomous pathways by modulation of signaling pathways. Interestingly, genetic and pharmacologic analysis of factors able to modulate lifespan and healthspan in model organisms and even humans have identified several key signaling pathways including IGF-1, NF-κB, FOXO3, mTOR, Nrf-2 and sirtuins. This review will discuss the roles of several of these key signaling pathways, in particular NF-κB and Nrf2, in modulating ageing and age-related diseases.
Topics: Aging; Animals; Apoptosis; Cellular Senescence; Humans; Longevity; NF-E2-Related Factor 2; NF-kappa B; Signal Transduction
PubMed: 30888655
DOI: 10.1007/978-981-13-3681-2_9 -
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 -
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 -
EMBO Molecular Medicine Dec 2019Organismal ageing is a complex process driving progressive impairment of functionality and regenerative potential of tissues. Cellular senescence is a state of stable... (Review)
Review
Organismal ageing is a complex process driving progressive impairment of functionality and regenerative potential of tissues. Cellular senescence is a state of stable cell cycle arrest occurring in response to damage and stress and is considered a hallmark of ageing. Senescent cells accumulate in multiple organs during ageing, contribute to tissue dysfunction and give rise to pathological manifestations. Senescence is therefore a defining feature of a variety of human age-related disorders, including cancer, and targeted elimination of these cells has recently emerged as a promising therapeutic approach to ameliorate tissue damage and promote repair and regeneration. In addition, in vivo identification of senescent cells has significant potential for early diagnosis of multiple pathologies. Here, we review existing senolytics, small molecules and drug delivery tools used in preclinical therapeutic strategies involving cellular senescence, as well as probes to trace senescent cells. We also review the clinical research landscape in senescence and discuss how identifying and targeting cellular senescence might positively affect pathological and ageing processes.
Topics: Aging; Animals; Cellular Senescence; Humans; Translational Research, Biomedical
PubMed: 31746100
DOI: 10.15252/emmm.201810234 -
Experimental Eye Research Jun 2022Ageing has been defined as a specific individual plasticity and remodeling capacity to the environment' insults and stimuli. The precise physiology of aging is not... (Review)
Review
Ageing has been defined as a specific individual plasticity and remodeling capacity to the environment' insults and stimuli. The precise physiology of aging is not entirely understood. Several theories have been proposed and included programmed cell death, genetic mutations, the epigenetic clock, wear-and-tear and free radicals. Ocular surface represents a complex morpho-functional unit composed of different tissues that strictly interact to preserve homeostasis and function. Ageing severely disrupts this system by means of inflammaging and immunosenescence, leading to ocular surface failure in older population.
Topics: Aged; Aging; Apoptosis; Humans; Immunosenescence; Inflammation
PubMed: 35307396
DOI: 10.1016/j.exer.2022.109035 -
Molecular Oncology Sep 2022Advancing age is a major risk factor for malignant transformation and the development of cancer. As such, over 50% of neoplasms occur in individuals over the age of 70.... (Review)
Review
Advancing age is a major risk factor for malignant transformation and the development of cancer. As such, over 50% of neoplasms occur in individuals over the age of 70. The pathologies of both ageing and cancer have been characterized by respective groups of molecular hallmarks, and while some features are divergent between the two pathologies, several are shared. Perturbed mitochondrial function is one such common hallmark, and this observation therefore suggests that mitochondrial alterations may be of significance in age-related cancer development. There is now considerable evidence documenting the accumulation of somatic mitochondrial DNA (mtDNA) mutations in ageing human postmitotic and replicative tissues. Similarly, mutations of the mitochondrial genome have been reported in human cancers for decades. The plethora of functions in which mitochondria partake, such as oxidative phosphorylation, redox balance, apoptosis and numerous biosynthetic pathways, manifests a variety of ways in which alterations in mtDNA may contribute to tumour growth. However, the specific mechanisms by which mtDNA mutations contribute to tumour progression remain elusive and often contradictory. This review aims to consolidate current knowledge and describe future direction within the field.
Topics: Aging; DNA, Mitochondrial; Humans; Mitochondria; Mutation; Neoplasms
PubMed: 35842901
DOI: 10.1002/1878-0261.13291