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Aging Cell Sep 2021Advanced age is the main common risk factor for cancer, cardiovascular disease and neurodegeneration. Yet, more is known about the molecular basis of any of these groups... (Review)
Review
Advanced age is the main common risk factor for cancer, cardiovascular disease and neurodegeneration. Yet, more is known about the molecular basis of any of these groups of diseases than the changes that accompany ageing itself. Progress in molecular ageing research was slow because the tools predicting whether someone aged slowly or fast (biological age) were unreliable. To understand ageing as a risk factor for disease and to develop interventions, the molecular ageing field needed a quantitative measure; a clock for biological age. Over the past decade, a number of age predictors utilising DNA methylation have been developed, referred to as epigenetic clocks. While they appear to estimate biological age, it remains unclear whether the methylation changes used to train the clocks are a reflection of other underlying cellular or molecular processes, or whether methylation itself is involved in the ageing process. The precise aspects of ageing that the epigenetic clocks capture remain hidden and seem to vary between predictors. Nonetheless, the use of epigenetic clocks has opened the door towards studying biological ageing quantitatively, and new clocks and applications, such as forensics, appear frequently. In this review, we will discuss the range of epigenetic clocks available, their strengths and weaknesses, and their applicability to various scientific queries.
Topics: Aging; Animals; Epigenesis, Genetic; Humans
PubMed: 34415665
DOI: 10.1111/acel.13452 -
Nature Communications Aug 2023Cardiovascular ageing is a process that begins early in life and leads to a progressive change in structure and decline in function due to accumulated damage across...
Cardiovascular ageing is a process that begins early in life and leads to a progressive change in structure and decline in function due to accumulated damage across diverse cell types, tissues and organs contributing to multi-morbidity. Damaging biophysical, metabolic and immunological factors exceed endogenous repair mechanisms resulting in a pro-fibrotic state, cellular senescence and end-organ damage, however the genetic architecture of cardiovascular ageing is not known. Here we use machine learning approaches to quantify cardiovascular age from image-derived traits of vascular function, cardiac motion and myocardial fibrosis, as well as conduction traits from electrocardiograms, in 39,559 participants of UK Biobank. Cardiovascular ageing is found to be significantly associated with common or rare variants in genes regulating sarcomere homeostasis, myocardial immunomodulation, and tissue responses to biophysical stress. Ageing is accelerated by cardiometabolic risk factors and we also identify prescribed medications that are potential modifiers of ageing. Through large-scale modelling of ageing across multiple traits our results reveal insights into the mechanisms driving premature cardiovascular ageing and reveal potential molecular targets to attenuate age-related processes.
Topics: Humans; Aging; Electrocardiography; Cellular Senescence; Aging, Premature; Myocardium
PubMed: 37604819
DOI: 10.1038/s41467-023-40566-6 -
Tidsskrift For Den Norske Laegeforening... Jun 2024Good sexual health promotes quality of life and coping skills, and this also applies to older adults. This clinical review article presents updated knowledge on older... (Review)
Review
Good sexual health promotes quality of life and coping skills, and this also applies to older adults. This clinical review article presents updated knowledge on older adults' sexuality, normal challenges related to ageing and conjugal relationships, and sexual challenges caused by chronic diseases, adverse effects of medications, and cognitive failure. The review describes measures to improve sexual health. Healthcare personnel should take the initiative to talk about sexual health with older adults.
Topics: Humans; Sexual Health; Aged; Aging; Female; Male; Quality of Life; Sexual Behavior; Sexual Dysfunction, Physiological; Chronic Disease; Sexuality
PubMed: 38832621
DOI: 10.4045/tidsskr.23.0809 -
Mechanisms of Ageing and Development Sep 2023Ageing is a continuous process in life featuring progressive damage accumulation that leads to physiological decline, functional deterioration and ultimately death of an... (Review)
Review
Ageing is a continuous process in life featuring progressive damage accumulation that leads to physiological decline, functional deterioration and ultimately death of an organism. Based on the relatively close anatomical and physiological similarity to humans, the mouse has been proven as a valuable model organism in ageing research over the last decades. In this review, we survey methods and tools currently in use to assess ageing phenotypes in mice. We summarize a range of ageing-associated alterations detectable at two major levels of analysis: (1) physiology and pathophysiology and (2) molecular biomarkers. Age-sensitive phenotypes provided in this article may serve to inform future studies targeting various aspects of organismal ageing in mice. In addition, we discuss conceptual and technical challenges faced by previous ageing studies in mice and, where possible, provide recommendations on how to resolve some of these issues.
Topics: Humans; Mice; Animals; Aging; Biomarkers; Phenotype
PubMed: 37454704
DOI: 10.1016/j.mad.2023.111852 -
GeroScience Oct 2022One of the most striking findings in biogerontology in the 2010s was the demonstration that elimination of senescent cells delays many late-life diseases and extends... (Review)
Review
One of the most striking findings in biogerontology in the 2010s was the demonstration that elimination of senescent cells delays many late-life diseases and extends lifespan in mice. This implied that accumulation of senescent cells promotes late-life diseases, particularly through action of senescent cell secretions (the senescence-associated secretory phenotype, or SASP). But what exactly is a senescent cell? Subsequent to the initial characterization of cellular senescence, it became clear that, prior to aging, this phenomenon is in fact adaptive. It supports tissue remodeling functions in a variety of contexts, including embryogenesis, parturition, and acute inflammatory processes that restore normal tissue architecture and function, such as wound healing, tissue repair after infection, and amphibian limb regeneration. In these contexts, such cells are normal and healthy and not in any way senescent in the true sense of the word, as originally meant by Hayflick. Thus, it is misleading to refer to them as "senescent." Similarly, the common assertion that senescent cells accumulate with age due to stress and DNA damage is no longer safe, particularly given their role in inflammation-a process that becomes persistent in later life. We therefore suggest that it would be useful to update some terminology, to bring it into line with contemporary understanding, and to avoid future confusion. To open a discussion of this issue, we propose replacing the term cellular senescence with remodeling activation, and SASP with RASP (remodeling-associated secretory phenotype).
Topics: Animals; Mice; Cellular Senescence; Aging; Inflammation; Longevity
PubMed: 36068483
DOI: 10.1007/s11357-022-00652-x -
Sub-cellular Biochemistry 2023Age-related hearing loss (ARHL), or presbycusis, occurs in most mammals, humans included, with a different age of onset and magnitude of loss. It is associated with two...
Age-related hearing loss (ARHL), or presbycusis, occurs in most mammals, humans included, with a different age of onset and magnitude of loss. It is associated with two major symptoms: loss of sensitivity to sound, especially for high pitches, and a reduced ability to understand speech in background noise. This phenomenon involves both the peripheral structures of the inner ear and the central acoustic pathways. Several mechanisms have been identified as pro-ageing in the human cochlea. The main one is the oxidative stress. The inner ear physiological degeneration can be affected by both intrinsic conditions, such as genetic predisposition, and extrinsic ones, such as noise exposure. The magnitude of neuronal loss precedes and exceeds that of inner hair cell loss, which is also less important than the loss of outer hair cells. Patients with HL often develop atrophy of the temporal lobe (auditory cortex) and brain gliosis can contribute to the development of a central hearing loss. The presence of white matter hyperintensities (WMHs) on the MRI, which is radiologic representation of brain gliosis, can justify a central HL due to demyelination in the superior auditory pathways. Recently, the presence of WMHs has been correlated with the inability to correctly understand words in elderly with normal auditory thresholds.
Topics: Animals; Humans; Aged; Gliosis; Hearing; Aging; Cochlea; Presbycusis; Mammals
PubMed: 37120472
DOI: 10.1007/978-3-031-26576-1_12 -
Molecular Oncology Nov 2022Cellular senescence is a stress response elicited by different molecular insults. Senescence results in cell cycle exit and is characterised by multiple phenotypic... (Review)
Review
Cellular senescence is a stress response elicited by different molecular insults. Senescence results in cell cycle exit and is characterised by multiple phenotypic changes such as the production of a bioactive secretome. Senescent cells accumulate during ageing and are present in cancerous and fibrotic lesions. Drugs that selectively kill senescent cells (senolytics) have shown great promise for the treatment of age-related diseases. Senescence plays paradoxical roles in cancer. Induction of senescence limits cancer progression and contributes to therapy success, but lingering senescent cells fuel progression, recurrence, and metastasis. In this review, we describe the intricate relation between senescence and cancer. Moreover, we enumerate how current anticancer therapies induce senescence in tumour cells and how senolytic agents could be deployed to complement anticancer therapies. "One-two punch" therapies aim to first induce senescence in the tumour followed by senolytic treatment to target newly exposed vulnerabilities in senescent tumour cells. "One-two punch" represents an emerging and promising new strategy in cancer treatment. Future challenges of "one-two punch" approaches include how to best monitor senescence in cancer patients to effectively survey their efficacy.
Topics: Humans; Aging; Cellular Senescence; Neoplasms; Antineoplastic Agents
PubMed: 36065138
DOI: 10.1002/1878-0261.13312 -
Mechanisms of Ageing and Development Sep 2020
Topics: Aging; Chronic Disease; Homeostasis; Humans; Mitochondrial Dynamics; Mitophagy
PubMed: 32569605
DOI: 10.1016/j.mad.2020.111291 -
Nature Reviews. Nephrology Oct 2019Immunosenescence involves a series of ageing-induced alterations in the immune system and is characterized by two opposing hallmarks: defective immune responses and... (Review)
Review
Immunosenescence involves a series of ageing-induced alterations in the immune system and is characterized by two opposing hallmarks: defective immune responses and increased systemic inflammation. The immune system is modulated by intrinsic and extrinsic factors and undergoes profound changes in response to the ageing process. Immune responses are therefore highly age-dependent. Emerging data show that immunosenescence underlies common mechanisms responsible for several age-related diseases and is a plastic state that can be modified and accelerated by non-heritable environmental factors and pharmacological intervention. In the kidney, resident macrophages and fibroblasts are continuously exposed to components of the external environment, and the effects of cellular reprogramming induced by local immune responses, which accumulate with age, might have a role in the increased susceptibility to kidney disease among elderly individuals. Additionally, because chronic kidney disease, especially end-stage renal disease, is often accompanied by immunosenescence, which affects these patients independently of age, and many kidney diseases are strongly age-associated, treatment approaches that target immunosenescence might be particularly clinically relevant.
Topics: Aging; Animals; Humans; Immunosenescence; Kidney
PubMed: 31477915
DOI: 10.1038/s41581-019-0185-9 -
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