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Expert Opinion on Drug Discovery Feb 2020
Topics: Aging; Animals; Drug Discovery; Humans; Longevity
PubMed: 31822135
DOI: 10.1080/17460441.2020.1702965 -
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 -
Biogerontology Dec 2018
Topics: Aging; Cellular Senescence; Humans; Metabolomics; Microbiota; Proteomics
PubMed: 30288632
DOI: 10.1007/s10522-018-9776-2 -
Sub-cellular Biochemistry 2018Vitamin B contributes to the overall health and wellbeing, including that of energy metabolism, methylation, synthesis and DNA repair and proper immune function.... (Review)
Review
Vitamin B contributes to the overall health and wellbeing, including that of energy metabolism, methylation, synthesis and DNA repair and proper immune function. Deficiency in B vitamins has been linked to neurocognitive disorders, mitochondrial dysfunction, immune dysfunction and inflammatory conditions. In ageing populations B vitamin deficiency has been linked to cardiovascular disorders, cognitive dysfunction, osteoporosis and methylation disorders and can increase the risk of developing degenerative diseases, particularly cardiovascular disease, cognitive diseases and osteoporosis. Optimization of B vitamin status in the elderly may prove beneficial in the prevention of degenerative diseases. Here we discuss broadly the role of B vitamins in ageing.
Topics: Aging; Humans; Vitamin B Complex; Vitamin B Deficiency
PubMed: 30779018
DOI: 10.1007/978-981-13-2835-0_15 -
Trends in Endocrinology and Metabolism:... Feb 2019Increasing human life expectancy has posed increasing challenges for healthcare systems. As people age, they become more susceptible to chronic diseases, with an... (Review)
Review
Increasing human life expectancy has posed increasing challenges for healthcare systems. As people age, they become more susceptible to chronic diseases, with an increasing burden of multimorbidity, and the associated polypharmacy. Accumulating evidence from work with laboratory animals has shown that ageing is a malleable process that can be ameliorated by genetic and environmental interventions. Drugs that modulate the ageing process may delay or even prevent the incidence of multiple diseases of ageing. To identify novel, anti-ageing drugs, several studies have developed computational drug-repurposing strategies. We review published studies showing the potential of current drugs to modulate ageing. Future studies should integrate current knowledge with multi-omics, health records, and drug safety data to predict drugs that can improve health in late life.
Topics: Aging; Animals; Humans; Life Expectancy; Longevity
PubMed: 30581056
DOI: 10.1016/j.tem.2018.11.005 -
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 -
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 2018It is now widely recognised that ageing and its associated functional decline are regulated by a wide range of molecules that fit into specific cellular pathways. Here,... (Review)
Review
It is now widely recognised that ageing and its associated functional decline are regulated by a wide range of molecules that fit into specific cellular pathways. Here, we describe several of the evolutionary conserved cellular signalling pathways that govern organismal ageing and discuss how their identification, and work on the individual molecules that contribute to them, has aided in the design of therapeutic strategies to alleviate the adverse effects of ageing and age-related disease.
Topics: Aging; Evolution, Molecular; Signal Transduction
PubMed: 30779014
DOI: 10.1007/978-981-13-2835-0_11 -
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 -
Mechanisms of Ageing and Development Sep 2018
Topics: Aging; Animals; Epigenesis, Genetic; Epigenomics; Humans
PubMed: 29778757
DOI: 10.1016/j.mad.2018.05.005