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Histology and Histopathology Jun 2023Ageing is a biological process caused by the malfunctioning of multiple cellular mechanisms, ascribable to nine hallmarks: genomic instability, telomere attrition,... (Review)
Review
Ageing is a biological process caused by the malfunctioning of multiple cellular mechanisms, ascribable to nine hallmarks: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. These ageing pillars have three common traits: (i) they appear during normal ageing; (ii) their experimental intensification accelerates ageing; and (iii) their experimental reduction delays ageing. The evidence that the elderly are more prone to develop pathologies such as cancer, diabetes and degenerative diseases, together with data showing that the elderly population is steadily increasing, has stimulated an important effort to find specific countermeasures to physiological ageing. Unfortunately, the investigation of ageing processes and the search for countermeasures in humans is very difficult. Therefore, researchers must rely on a wide range of experimental models that span from unicellular to more complex organisms. Unfortunately, experimental models are not devoid of pitfalls, flaws or obstacles that can have an impact in ageing research. In the present review we describe the most exploited experimental models in the field, such as in vitro, animal and human models, highlighting the characteristics that justify their application in the laboratory routine, and translation to human research.
Topics: Aged; Animals; Humans; Aging; Cellular Senescence; Cell Communication; Stem Cells; Telomere
PubMed: 36602135
DOI: 10.14670/HH-18-576 -
Developmental Biology Aug 2021Recent advances in rapid medical detection and diagnostic technology have extended both human health and life expectancy. However, ageing remains one of the critical... (Review)
Review
Recent advances in rapid medical detection and diagnostic technology have extended both human health and life expectancy. However, ageing remains one of the critical risk factors in contributing to major incapacitating and fatal conditions, including cancer and neurodegeneration. Therefore, it is vital to study how ageing attributes to (or participates in) endangering human health via infliction of age-related diseases and what must be done to tackle this intractable process. This review encompasses the most recent literature elaborating the role of cell competition (CC) during ageing. CC is a process that occurs between two heterogeneous populations, where the cells with higher fitness levels have a competitive advantage over the neighbouring cells that have comparatively lower fitness levels. This interaction results in the selection of the fit cells, within a population, and elimination of the viable yet suboptimal cells. Therefore, it is tempting to speculate that, if this quality control mechanism works efficiently throughout life, can it ultimately lead to a healthier ageing and extended lifespan. Furthermore, the review aims to collate all the important state of the art publications that provides evidence of the relevance of CC in dietary restriction, stem cell dynamics, and cell senescence, thus, prompting us to advocate its contribution and in exploring new avenues and opportunities in fighting age-related conditions.
Topics: Aging; Animals; Cell Communication; Cell Competition; Cellular Senescence; Humans; Neoplasms
PubMed: 33753080
DOI: 10.1016/j.ydbio.2021.03.009 -
Ageing Research Reviews Jul 2023Ageing is a physiological/pathological process accompanied by the progressive damage of cell function, triggering various ageing-related disorders. Phosphatidylinositol... (Review)
Review
Ageing is a physiological/pathological process accompanied by the progressive damage of cell function, triggering various ageing-related disorders. Phosphatidylinositol 3-kinase (PI3K), which serves as one of the central regulators of ageing, is closely associated with cellular characteristics or molecular features, such as genome instability, telomere erosion, epigenetic alterations, and mitochondrial dysfunction. In this review, the PI3K signalling pathway was firstly thoroughly explained. The link between ageing pathogenesis and the PI3K signalling pathway was then summarized. Finally, the key regulatory roles of PI3K in ageing-related illnesses were investigated and stressed. In summary, we revealed that drug development and clinical application targeting PI3K is one of the focal points for delaying ageing and treating ageing-related diseases in the future.
Topics: Phosphatidylinositol 3-Kinase; Humans; Animals; Signal Transduction; Aging; Neurodegenerative Diseases; Metabolic Diseases; Heart Diseases; Neoplasms
PubMed: 37245633
DOI: 10.1016/j.arr.2023.101963 -
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 -
F1000Research 2019The field of aging research has progressed significantly over the past decades. Exogenously and endogenously inflicted molecular damage ranging from genotoxic to... (Review)
Review
The field of aging research has progressed significantly over the past decades. Exogenously and endogenously inflicted molecular damage ranging from genotoxic to organellar damage drives the aging process. Repair mechanisms and compensatory responses counteract the detrimental consequences of the various damage types. Here, we discuss recent progress in understanding cellular mechanisms and interconnections between signaling pathways that control longevity. We summarize cell-autonomous and non-cell-autonomous mechanisms that impact the cellular and organismal aging process.
Topics: Aging; DNA Damage; Humans; Longevity; Signal Transduction
PubMed: 31448092
DOI: 10.12688/f1000research.19610.1 -
Mechanisms of Ageing and Development Dec 2017MicroRNAs (miRNAs) are short, non-coding RNAs that regulate the expression of mRNA targets and play a part in the post-transcriptional silencing. To date, the prominent... (Review)
Review
MicroRNAs (miRNAs) are short, non-coding RNAs that regulate the expression of mRNA targets and play a part in the post-transcriptional silencing. To date, the prominent roles of miRNAs in stem cells have been investigated in a wide range of biological processes, including self-renewal, differentiation and proliferation. In this commentary, we first demonstrate the causes and mechanisms of somatic stem cell aging in a new aspect of miRNAs. The functions of stem cells decline with age in diverse tissues due to cellular damages and congenital disorders. The somatic stem cells exhibit type-specific phenotypes with cellular senescence during the aging process. We explore the specific miRNAs regulating stem cell aging and age-related diseases. The functional investigations of the miRNAs in somatic stem cells and degenerative diseases might facilitate the translation of knowledge into clinical practice for the regulation of stem cell aging and aging-related diseases.
Topics: Age Factors; Aging; Animals; Cell Differentiation; Cell Lineage; Cellular Senescence; Disease; Gene Expression Regulation; Humans; MicroRNAs; Phenotype; Signal Transduction; Stem Cells
PubMed: 28847486
DOI: 10.1016/j.mad.2017.08.013 -
Mechanisms of Ageing and Development Mar 2018Cellular senescence was first described by Hayflick and Moorhead in the 1960s as the irreversible arrest of cells following prolonged cultivation. Telomere shortening is... (Review)
Review
Cellular senescence was first described by Hayflick and Moorhead in the 1960s as the irreversible arrest of cells following prolonged cultivation. Telomere shortening is the key mechanism driving replicative senescence in human fibroblasts. Later, pioneering work by Olivier Toussaint and others showed that stress plays a major role in the induction of senescence in vitro, a phenomenon known as stress-induced premature senescence or SIPS. It is also now widely accepted that senescence plays a role in vivo. An emerging body of evidence from animal models, and particularly mice, has demonstrated an important role for senescence in several processes such as embryonic development, wound healing, tumour suppression and ageing. However, mostly due to a lack of availability of tissues and specific markers, less is known about the importance of cell senescence in humans. In this review, we summarize some of the key findings in the field of senescence, stress-induced senescence and telomeres. We focus particularly on the role of telomere dysfunction and senescence during the ageing process as well as potential interventions, including pharmacological approaches like telomerase activators and senolytics, to counteract their detrimental effects in ageing and disease.
Topics: Aging; Cellular Senescence; Embryonic Development; Humans; Neoplasms; Stress, Physiological; Telomere Homeostasis; Wound Healing
PubMed: 28688962
DOI: 10.1016/j.mad.2017.07.001 -
Current Vascular Pharmacology 2021Aging has been considered to be the most important non-modifiable risk factor for stroke and death. Changes in circulation factors in the systemic environment, cellular... (Review)
Review
Aging has been considered to be the most important non-modifiable risk factor for stroke and death. Changes in circulation factors in the systemic environment, cellular senescence and artery hypertension during human ageing have been investigated. Exosomes are nanosize membrane vesicles that can regulate target cell functions via delivering their carried bioactive molecules (e.g. protein, mRNA, and microRNAs). In the central nervous system, exosomes and exosomal microRNAs play a critical role in regulating neurovascular function and are implicated in stroke initiation and progression. MicroRNAs are small non-coding RNAs that have been reported to play critical roles in various biological processes. Recently, evidence has shown that microRNAs are packaged into exosomes and can be secreted into the systemic and tissue environment. Circulating microRNAs participate in cellular senescence and contribute to age-associated stroke. Here, we provide an overview of current knowledge on exosomes and their carried microRNAs in the regulation of cellular and organismal ageing processes, demonstrating the potential role of exosomes and their carried microRNAs in age-associated stroke.
Topics: Aging; Cellular Senescence; Exosomes; Humans; MicroRNAs; Stroke
PubMed: 33563154
DOI: 10.2174/1570161119666210208202621 -
Mechanisms of Ageing and Development Sep 2018Aging has been associated with iron retention in many cell types, including the neurons, promoting neurodegeneration by ferroptosis. Excess intracellular iron... (Review)
Review
Aging has been associated with iron retention in many cell types, including the neurons, promoting neurodegeneration by ferroptosis. Excess intracellular iron accelerates aging by damaging the DNA and blocking genomic repair systems, a process we define as ferrosenescence. Novel neuroimaging and proteomic techniques have pinpointed indicators of both iron retention and ferrosenescence, allowing for their early correction, potentially bringing prevention of neurodegenerative disorders within reach. In this review, we take a closer look at the early markers of iron dyshomeostasis in neurodegenerative disorders, focusing on preventive strategies based on nutritional and microbiome manipulations.
Topics: Aging; Animals; DNA Damage; DNA Repair; Humans; Iron; Neurodegenerative Diseases
PubMed: 29180225
DOI: 10.1016/j.mad.2017.11.012 -
Mammalian Genome : Official Journal of... Aug 2016Stem cells maintain homeostasis in all regenerating tissues during the lifespan of an organism. Thus, age-related functional decline of such tissues is likely to be at... (Review)
Review
Stem cells maintain homeostasis in all regenerating tissues during the lifespan of an organism. Thus, age-related functional decline of such tissues is likely to be at least partially explained by molecular events occurring in the stem cell compartment. Some of these events involve epigenetic changes, which may dictate how an aging genome can lead to differential gene expression programs. Recent technological advances have made it now possible to assess the genome-wide distribution of an ever-increasing number of epigenetic marks. As a result, the hypothesis that there may be a causal role for an altered epigenome contributing to the functional decline of cells, tissues, and organs in aging organisms can now be explored. In this paper, we review recent developments in the field of epigenetic regulation of stem cells, and how this may contribute to aging.
Topics: Aging; Cellular Senescence; DNA Methylation; Epigenesis, Genetic; Genome; Homeostasis; Humans; Regeneration; Stem Cells
PubMed: 27229519
DOI: 10.1007/s00335-016-9645-8