-
Mechanisms of Ageing and Development Jun 2022Ageing is associated with modified function of both innate and adaptive immunity. It is believed that changes occurring in ageing immune system are responsible for... (Review)
Review
Ageing is associated with modified function of both innate and adaptive immunity. It is believed that changes occurring in ageing immune system are responsible for increased severity and deadliness of COVID-19 in the elderly. Although supported by statistics and epidemiology, these finding do not compute at the mechanistic level as depending solely on chronological and biological ageing. The phenomena describing changes in the aging immune system are immunosenescence and inflammageing, which develop in time depending on challenges to the individual immune system (immunobiography). Thus, "richer" immunobiography (in addition to other factors, including genetic, epigenetics or metabolic) may adversely affect the reactivity to the SARS-CoV-2 not only at later decades of life, but also earlier, in young and middle-aged individuals. On the other hand, infection with SARS-CoV-2 is affecting the function of both innate and adaptive branches of the immune system, adding to the individual immunobiography. Summarizing, immunosenescence and inflammaging may aggravate, but also may be aggravated by SARS-CoV-2 infection.
Topics: Adaptive Immunity; Aged; Aging; COVID-19; Humans; Immunosenescence; Middle Aged; SARS-CoV-2
PubMed: 35378106
DOI: 10.1016/j.mad.2022.111672 -
Scientific Reports May 2024Alongside rapid population ageing, we are experiencing increasing numbers of people with cognitive impairment and dementia. There is great scientific effort being...
Alongside rapid population ageing, we are experiencing increasing numbers of people with cognitive impairment and dementia. There is great scientific effort being committed to understanding cognitive and brain functioning, with the aim of helping to promote healthy ageing and independence, and improve quality of life. This Cognitive Ageing Collection brings together cutting-edge research using a variety of methods and from diverse disciplinary perspectives, with example topics including cognitive strategies, genetic risk factors, and emotion regulation. Articles in the Collection highlight advances in our understanding of cognitive and brain health, and outline important directions for future research.
Topics: Humans; Cognitive Aging; Cognition; Aging
PubMed: 38740780
DOI: 10.1038/s41598-024-60763-7 -
Nature Aug 2017It has been proposed that the hypothalamus helps to control ageing, but the mechanisms responsible remain unclear. Here we develop several mouse models in which...
It has been proposed that the hypothalamus helps to control ageing, but the mechanisms responsible remain unclear. Here we develop several mouse models in which hypothalamic stem/progenitor cells that co-express Sox2 and Bmi1 are ablated, as we observed that ageing in mice started with a substantial loss of these hypothalamic cells. Each mouse model consistently displayed acceleration of ageing-like physiological changes or a shortened lifespan. Conversely, ageing retardation and lifespan extension were achieved in mid-aged mice that were locally implanted with healthy hypothalamic stem/progenitor cells that had been genetically engineered to survive in the ageing-related hypothalamic inflammatory microenvironment. Mechanistically, hypothalamic stem/progenitor cells contributed greatly to exosomal microRNAs (miRNAs) in the cerebrospinal fluid, and these exosomal miRNAs declined during ageing, whereas central treatment with healthy hypothalamic stem/progenitor cell-secreted exosomes led to the slowing of ageing. In conclusion, ageing speed is substantially controlled by hypothalamic stem cells, partially through the release of exosomal miRNAs.
Topics: Aging; Animals; Cellular Microenvironment; Exosomes; Hypothalamus; I-kappa B Proteins; Inflammation; Longevity; Male; Mice; Mice, Inbred C57BL; MicroRNAs; Neural Stem Cells; Polycomb Repressive Complex 1; Proto-Oncogene Proteins; SOXB1 Transcription Factors; Time Factors
PubMed: 28746310
DOI: 10.1038/nature23282 -
The Journals of Gerontology. Series A,... Sep 2020Aging is a powerful risk factor for the development of many chronic diseases including dementia. Research based on disease models of dementia have yet to yield effective... (Review)
Review
Aging is a powerful risk factor for the development of many chronic diseases including dementia. Research based on disease models of dementia have yet to yield effective treatments, therefore it is opportune to consider whether the aging process itself might be a potential therapeutic target for the treatment and prevention of dementia. Numerous cellular and molecular pathways have been implicated in the aging process and compounds that target these processes are being developed to slow aging and delay the onset of age-associated conditions. A few particularly promising therapeutic agents have been shown to influence many of the main hallmarks of aging and increase life span in rodents. Here we discuss the evidence that some of these antiaging compounds may beneficially affect brain aging and thereby lower the risk for dementia.
Topics: Aging; Animals; Cognitive Dysfunction; Dementia; Humans
PubMed: 31125402
DOI: 10.1093/gerona/glz135 -
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 -
Ageing Research Reviews Feb 2023The destructive effects of coronavirus disease 2019 (COVID-19) on the elderly and people with cardiovascular disease have been proven. New findings shed light on the... (Review)
Review
The destructive effects of coronavirus disease 2019 (COVID-19) on the elderly and people with cardiovascular disease have been proven. New findings shed light on the role of aging pathways on life span and health age. New therapies that focus on aging-related pathways may positively impact the treatment of this acute respiratory infection. Using new therapies that boost the level of the immune system can support the elderly with co-morbidities against the acute form of COVID-19. This article discusses the effect of the aging immune system against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the pathways affecting this severity of infection.
Topics: Humans; Aged; COVID-19; Immunosenescence; SARS-CoV-2; Aging; Immune System
PubMed: 36516928
DOI: 10.1016/j.arr.2022.101818 -
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 -
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