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Physiological Research Sep 2020Ageing is accompanied by deterioration in physical condition and a number of physiological processes and thus a higher risk of a range of diseases and disorders. In... (Review)
Review
Ageing is accompanied by deterioration in physical condition and a number of physiological processes and thus a higher risk of a range of diseases and disorders. In particular, we focused on the changes associated with aging, especially the role of small molecules, their role in physiological and pathophysiological processes and potential treatment options. Our previously published results and data from other authors lead to the conclusion that these unwanted changes are mainly linked to the hypothalamic-pituitary-adrenal axis can be slowed down, stopped, or in some cases even reversed by an appropriate treatment, but especially by a life-management adjustment.
Topics: Aging; Animals; Hormones; Humans; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Receptors, Cell Surface; Small Molecule Libraries
PubMed: 33094624
DOI: 10.33549/physiolres.934523 -
Nature Cell Biology Feb 2022Ageing organisms accumulate senescent cells that are thought to contribute to body dysfunction. Telomere shortening and damage are recognized causes of cellular... (Review)
Review
Ageing organisms accumulate senescent cells that are thought to contribute to body dysfunction. Telomere shortening and damage are recognized causes of cellular senescence and ageing. Several human conditions associated with normal ageing are precipitated by accelerated telomere dysfunction. Here, we systematize a large body of evidence and propose a coherent perspective to recognize the broad contribution of telomeric dysfunction to human pathologies.
Topics: Age Factors; Aging; Animals; Cellular Senescence; DNA Damage; Humans; Noncommunicable Diseases; Telomere; Telomere Homeostasis; Telomere Shortening
PubMed: 35165420
DOI: 10.1038/s41556-022-00842-x -
Cells Nov 2019In contrast to the programmed nature of development, it is still a matter of debate whether aging is an adaptive and regulated process, or merely a consequence arising... (Comparative Study)
Comparative Study Review
In contrast to the programmed nature of development, it is still a matter of debate whether aging is an adaptive and regulated process, or merely a consequence arising from a stochastic accumulation of harmful events that culminate in a global state of reduced fitness, risk for disease acquisition, and death. Similarly unanswered are the questions of whether aging is reversible and can be turned into rejuvenation as well as how aging is distinguishable from and influenced by cellular senescence. With the discovery of beneficial aspects of cellular senescence and evidence of senescence being not limited to replicative cellular states, a redefinition of our comprehension of aging and senescence appears scientifically overdue. Here, we provide a factor-based comparison of current knowledge on aging and senescence, which we converge on four suggested concepts, thereby implementing the newly emerging cellular and molecular aspects of geroconversion and amitosenescence, and the signatures of a genetic state termed genosenium. We also address the possibility of an aging-associated secretory phenotype in analogy to the well-characterized senescence-associated secretory phenotype and delineate the impact of epigenetic regulation in aging and senescence. Future advances will elucidate the biological and molecular fingerprints intrinsic to either process.
Topics: Aging; Animals; Biomarkers; Cellular Senescence; Epigenesis, Genetic; Humans; Phenotype
PubMed: 31731770
DOI: 10.3390/cells8111446 -
Nature Reviews. Cancer Feb 2020Most cancers arise in individuals over the age of 60. As the world population is living longer and reaching older ages, cancer is becoming a substantial public health... (Review)
Review
Most cancers arise in individuals over the age of 60. As the world population is living longer and reaching older ages, cancer is becoming a substantial public health problem. It is estimated that, by 2050, more than 20% of the world's population will be over the age of 60 - the economic, healthcare and financial burdens this may place on society are far from trivial. In this Review, we address the role of the ageing microenvironment in the promotion of tumour progression. Specifically, we discuss the cellular and molecular changes in non-cancerous cells during ageing, and how these may contribute towards a tumour permissive microenvironment; these changes encompass biophysical alterations in the extracellular matrix, changes in secreted factors and changes in the immune system. We also discuss the contribution of these changes to responses to cancer therapy as ageing predicts outcomes of therapy, including survival. Yet, in preclinical studies, the contribution of the aged microenvironment to therapy response is largely ignored, with most studies designed in 8-week-old mice rather than older mice that reflect an age appropriate to the disease being modelled. This may explain, in part, the failure of many successful preclinical therapies upon their translation to the clinic. Overall, the intention of this Review is to provide an overview of the interplay that occurs between ageing cell types in the microenvironment and cancer cells and how this is likely to impact tumour metastasis and therapy response.
Topics: Aging; Animals; Cell Transformation, Neoplastic; Combined Modality Therapy; Disease Progression; Extracellular Matrix; Humans; Neoplasms; Stromal Cells; Treatment Outcome; Tumor Microenvironment
PubMed: 31836838
DOI: 10.1038/s41568-019-0222-9 -
Cells Jan 2022Acute inflammation is a physiological response to injury or infection, with a cascade of steps that ultimately lead to the recruitment of immune cells to clear invading... (Review)
Review
Acute inflammation is a physiological response to injury or infection, with a cascade of steps that ultimately lead to the recruitment of immune cells to clear invading pathogens and heal wounds. However, chronic inflammation arising from the continued presence of the initial trigger, or the dysfunction of signalling and/or effector pathways, is harmful to health. While successful ageing in older adults, including centenarians, is associated with low levels of inflammation, elevated inflammation increases the risk of poor health and death. Hence inflammation has been described as one of seven pillars of ageing. Age-associated sterile, chronic, and low-grade inflammation is commonly termed inflammageing-it is not simply a consequence of increasing chronological age, but is also a marker of biological ageing, multimorbidity, and mortality risk. While inflammageing was initially thought to be caused by "continuous antigenic load and stress", reports from the last two decades describe a much more complex phenomenon also involving cellular senescence and the ageing of the immune system. In this review, we explore some of the main sources and consequences of inflammageing in the context of immunosenescence and highlight potential interventions. In particular, we assess the contribution of cellular senescence to age-associated inflammation, identify patterns of pro- and anti-inflammatory markers characteristic of inflammageing, describe alterations in the ageing immune system that lead to elevated inflammation, and finally assess the ways that diet, exercise, and pharmacological interventions can reduce inflammageing and thus, improve later life health.
Topics: Aged; Aged, 80 and over; Aging; Biomarkers; Cellular Senescence; Humans; Immunosenescence; Inflammation
PubMed: 35159168
DOI: 10.3390/cells11030359 -
European Journal of Cell Biology Aug 2020Cellular theory of aging states that human aging is the result of cellular aging, in which an increasing proportion of cells reach senescence. Senescence, from the Latin... (Review)
Review
Cellular theory of aging states that human aging is the result of cellular aging, in which an increasing proportion of cells reach senescence. Senescence, from the Latin word senex, means "growing old," is an irreversible growth arrest which occurs in response to damaging stimuli, such as DNA damage, telomere shortening, telomere dysfunction and oncogenic stress leading to suppression of potentially dysfunctional, transformed, or aged cells. Cellular senescence is characterized by irreversible cell cycle arrest, flattened and enlarged morphology, resistance to apoptosis, alteration in gene expression and chromatin structure, expression of senescence associated- β-galactosidase (SA-β-gal) and acquisition of senescence associated secretory phenotype (SASP). In this review paper, different types of cellular senescence including replicative senescence (RS) which occurs due to telomere shortening and stress induced premature senescence (SIPS) which occurs in response to different types of stress in cells, are discussed. Biomarkers of cellular senescence and senescent assays including BrdU incorporation assay, senescence associated- β-galactosidase (SA-β-gal) and senescence-associated heterochromatin foci assays to detect senescent cells are also addressed.
Topics: Aging; Cellular Senescence; Humans
PubMed: 32800277
DOI: 10.1016/j.ejcb.2020.151108 -
The Lancet. Healthy Longevity Nov 2022Intrinsic capacity, a crucial concept in healthy ageing, is defined by WHO as "the composite of all the physical and mental capacities that an individual can draw on at... (Review)
Review
Intrinsic capacity, a crucial concept in healthy ageing, is defined by WHO as "the composite of all the physical and mental capacities that an individual can draw on at any point in time". Vitality capacity is considered the underlying physiological determinant of intrinsic capacity. To advance the measurement and monitoring of vitality capacity, a working group of WHO staff members and twenty experts representing six WHO regions was convened to discuss and clarify the attributes of vitality capacity and to develop a clear working definition of the concept. Potential biomarkers to measure vitality capacity were identified, and the following consensual working definition was developed: vitality capacity is a physiological state (due to normal or accelerated biological ageing processes) resulting from the interaction between multiple physiological systems, reflected in (the level of) energy and metabolism, neuromuscular function, and immune and stress response functions of the body.
Topics: Humans; Longevity; Health Status; Aging; Healthy Aging; World Health Organization
PubMed: 36356628
DOI: 10.1016/S2666-7568(22)00200-8 -
Nature Apr 2021Ageing is a complex, multifaceted process leading to widespread functional decline that affects every organ and tissue, but it remains unknown whether ageing has a... (Review)
Review
Ageing is a complex, multifaceted process leading to widespread functional decline that affects every organ and tissue, but it remains unknown whether ageing has a unifying causal mechanism or is grounded in multiple sources. Phenotypically, the ageing process is associated with a wide variety of features at the molecular, cellular and physiological level-for example, genomic and epigenomic alterations, loss of proteostasis, declining overall cellular and subcellular function and deregulation of signalling systems. However, the relative importance, mechanistic interrelationships and hierarchical order of these features of ageing have not been clarified. Here we synthesize accumulating evidence that DNA damage affects most, if not all, aspects of the ageing phenotype, making it a potentially unifying cause of ageing. Targeting DNA damage and its mechanistic links with the ageing phenotype will provide a logical rationale for developing unified interventions to counteract age-related dysfunction and disease.
Topics: Aging; Animals; Cell Differentiation; Cell Lineage; DNA Damage; DNA Repair; Humans
PubMed: 33911272
DOI: 10.1038/s41586-021-03307-7 -
The FEBS Journal Mar 2023The concept of geroscience is that since ageing is the greatest risk factor for many diseases and conditions, targeting the ageing process itself will have the greatest... (Review)
Review
The concept of geroscience is that since ageing is the greatest risk factor for many diseases and conditions, targeting the ageing process itself will have the greatest impact on human health. Of the hallmarks of ageing, cellular senescence has emerged as a druggable therapeutic target for extending healthspan in model organisms. Cellular senescence is a cell state of irreversible proliferative arrest driven by different types of stress, including oncogene-induced stress. Many senescent cells (SnCs) develop a senescent-associated secretory phenotype (SASP) comprising pro-inflammatory cytokines, chemokines, proteases, bioactive lipids, inhibitory molecules, extracellular vesicles, metabolites, lipids and other factors, able to promote chronic inflammation and tissue dysfunction. SnCs up-regulate senescent cell anti-apoptotic pathways (SCAPs) that prevent them from dying despite the accumulation of damage to DNA and other organelles. These SCAPs and other pathways altered in SnCs represent therapeutic targets for the development of senotherapeutic drugs that induce selective cell death of SnCs, specifically termed senolytics or suppress markers of senescence, in particular the SASP, termed senomorphics. Here, we review the current state of the development of senolytics and senomorphics for the treatment of age-related diseases and disorders and extension of healthy longevity. In addition, the challenges of documenting senolytic and senomorphic activity in pre-clinical models and the current state of the clinical application of the different senotherapeutics will be discussed.
Topics: Humans; Senotherapeutics; Cellular Senescence; Aging; Longevity; Lipids
PubMed: 35015337
DOI: 10.1111/febs.16350 -
Ageing Research Reviews Jan 2023Major depressive disorder (MDD) is characterized by psychological and physiological manifestations contributing to the disease severity and outcome. In recent years,... (Review)
Review
Major depressive disorder (MDD) is characterized by psychological and physiological manifestations contributing to the disease severity and outcome. In recent years, several lines of evidence have suggested that individuals with MDD have an elevated risk of age-related adverse outcomes across the lifespan. This review provided evidence of a significant overlap between the biological abnormalities in MDD and biological changes commonly observed during the aging process (i.e., hallmarks of biological aging). Based on such evidence, we formulate a mechanistic model showing how abnormalities in the hallmarks of biological aging can be a common denominator and mediate the elevated risk of age-related health outcomes commonly observed in MDD. Finally, we proposed a roadmap for novel studies to investigate the intersection between the biology of aging and MDD, including the use of geroscience-guided interventions, such as senolytics, to delay or improve major depression by targeting biological aging.
Topics: Humans; Depressive Disorder, Major; Depression; Aging; Longevity
PubMed: 36410621
DOI: 10.1016/j.arr.2022.101805