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The FEBS Journal Mar 2023The contribution of cellular senescence to a diverse range of biological processes, including normal physiology, ageing, and pathology were long overlooked but have now...
The contribution of cellular senescence to a diverse range of biological processes, including normal physiology, ageing, and pathology were long overlooked but have now taken centre stage. In this Editorial, we will briefly outline the review and original work articles contained in The FEBS Journal's Special Issue on Senescence in Ageing and Disease. It is beginning to be appreciated that senescent cells can exert both beneficial and adverse effects following tissue injury. Additionally, while these cells play critical roles for maintaining a healthy physiology, they also promote ageing and certain pathological conditions (including developmental disorders). Progress has been made in re-defining and identifying senescent cells, especially in slow-proliferating or terminally differentiated tissues, such as the brain and cardiovascular system. Novel approaches and techniques for isolating senescent cells will greatly increase our appreciation for senescent properties in tissues. The inter-organ communication between senescent cells and other residents of the tissue microenvironment, via the senescence-associated secretory phenotype (SASP), is a focus of several reviews in this Special Issue. The importance of the SASP in promoting tumour development and the evolution of SARS CoV-2 variants is also highlighted. In one of the two original articles included in the issue, the impact of dietary macronutrients and the presence of senescent cells in mice is investigated. Lastly, we continue to deepen our understanding on the use of senolytics and senomorphics to specifically target senescent cells or their secreted components, respectively, which is discussed in several of the reviews included here.
Topics: Animals; Mice; COVID-19; Cellular Senescence; Aging; Cell Differentiation; Brain
PubMed: 36856679
DOI: 10.1111/febs.16735 -
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 -
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 -
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 -
Ageing Research Reviews Sep 2015Cardiac aging is an intrinsic process that results in impaired cardiac function, along with cellular and molecular changes. These degenerative changes are intimately... (Review)
Review
Cardiac aging is an intrinsic process that results in impaired cardiac function, along with cellular and molecular changes. These degenerative changes are intimately associated with quality control mechanisms. This review provides a general overview of the clinical and cellular changes which manifest in cardiac aging, and the quality control mechanisms involved in maintaining homeostasis and retarding aging. These mechanisms include autophagy, ubiquitin-mediated turnover, apoptosis, mitochondrial quality control and cardiac matrix homeostasis. Finally, we discuss aging interventions that have been observed to impact cardiac health outcomes. These include caloric restriction, rapamycin, resveratrol, GDF11, mitochondrial antioxidants and cardiolipin-targeted therapeutics. A greater understanding of the quality control mechanisms that promote cardiac homeostasis will help to understand the benefits of these interventions, and hopefully lead to further improved therapeutic modalities.
Topics: Aging; Animals; DNA Repair; Diet; Heart; Humans; Quality Control
PubMed: 25702865
DOI: 10.1016/j.arr.2015.02.003 -
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 -
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 -
Journal of Cellular and Molecular... Sep 2023We are facing a growing aging population, along with increasing pressure on health systems, caused by the impact of chronic co-morbidities (i.e. cancer, cardiovascular... (Review)
Review
We are facing a growing aging population, along with increasing pressure on health systems, caused by the impact of chronic co-morbidities (i.e. cancer, cardiovascular and neurodegenerative diseases) and functional disabilities as people age. Relatively simple preventive lifestyle interventions, such as dietary restriction and physical exercise, are important contributors to active and healthy aging in the general population. However, as shown in model organisms or in 'in vitro' conditions, lifestyle-independent interventions may have additional health benefits and can even be conceived as possible reversers of the aging process. Thus, pharmaceutical laboratories, research institutes, and universities are putting more and more effort into finding new molecular pathways and druggable targets to develop gerotherapeutics. One approach is to target the driving mechanisms of aging, some of which, like cellular senescence and impaired autophagy, we discussed in an update on the biology of aging at AgingFit 2023 in Lille, France. We underline the importance of carefully and extensively testing senotherapeutics, given the pleiotropism and heterogeneity of targeted senescent cells within different organs, at different time frames. Other druggable targets emerging from new putative mechanisms, like those based on transcriptome imbalance, nucleophagy, protein phosphatase depletion, glutamine metabolism, or seno-antigenicity, have been evidenced by recent preclinical studies in classical models of aging but need to be validated in humans. Finally, we highlight several approaches in the discovery of biomarkers of healthy aging, as well as for the prediction of neurodegenerative diseases and the evaluation of rejuvenation strategies.
Topics: Humans; Aged; Longevity; Aging; Medicine; Biomedical Research; Cellular Senescence
PubMed: 37610311
DOI: 10.1111/jcmm.17912 -
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