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International Journal of Molecular... Sep 2018Ageing is a major risk factor for developing many neurodegenerative diseases. Cellular senescence is a homeostatic biological process that has a key role in driving... (Review)
Review
Ageing is a major risk factor for developing many neurodegenerative diseases. Cellular senescence is a homeostatic biological process that has a key role in driving ageing. There is evidence that senescent cells accumulate in the nervous system with ageing and neurodegenerative disease and may predispose a person to the appearance of a neurodegenerative condition or may aggravate its course. Research into senescence has long been hindered by its variable and cell-type specific features and the lack of a universal marker to unequivocally detect senescent cells. Recent advances in senescence markers and genetically modified animal models have boosted our knowledge on the role of cellular senescence in ageing and age-related disease. The aim now is to fully elucidate its role in neurodegeneration in order to efficiently and safely exploit cellular senescence as a therapeutic target. Here, we review evidence of cellular senescence in neurons and glial cells and we discuss its putative role in Alzheimer's disease, Parkinson's disease and multiple sclerosis and we provide, for the first time, evidence of senescence in neurons and glia in multiple sclerosis, using the novel GL13 lipofuscin stain as a marker of cellular senescence.
Topics: Aging; Animals; Cellular Senescence; Humans; Neurodegenerative Diseases
PubMed: 30261683
DOI: 10.3390/ijms19102937 -
Current Opinion in Clinical Nutrition... Jan 2016This article reviews the impact of ageing on the gastrointestinal tract, including effects on the absorption of nutrients and drugs and the gastrointestinal tract... (Review)
Review
PURPOSE OF REVIEW
This article reviews the impact of ageing on the gastrointestinal tract, including effects on the absorption of nutrients and drugs and the gastrointestinal tract defence system against ingested pathogens.
RECENT FINDINGS
Recent publications support earlier observations of an age-related selective decline in gut function including changes in taste, oesophageal sphincter motility, gastric emptying, and neurons of the myenteric plexus related to gut transit which may impact the nutritional status. Ageing is also associated with structural and functional mucosal defence defects, diminished abilities to generate protective immunity, and increased incidence of inflammation and oxidative stress. A number of gastrointestinal disorders occur more frequently in the elderly population.
SUMMARY
Alterations in gut function with ageing have particular implications for oesophageal, gastric, and colonic motility. Older individuals are particularly susceptible to malnutrition, postprandial hypotension, dysphagia, constipation, and faecal incontinence. Decrease in the number of nerve cells of the myenteric plexus that impact digestive absorption and the surface area of the small intestine because of degeneration of villi may lead to blunted absorption of nutrients. Impairment of the intestinal immune system as a result of ageing, including the mucosal layer of the gastrointestinal tract, appears to be a significant contributor to the age-related increase in the incidence and severity of infections.
Topics: Aging; Gastrointestinal Motility; Gastrointestinal Tract; Humans; Infections; Intestinal Absorption; Intestinal Mucosa; Nutritional Status
PubMed: 26560524
DOI: 10.1097/MCO.0000000000000238 -
Zeitschrift Fur Gerontologie Und... Sep 2019As population ageing takes place around the world, research on attitudes toward ageing and older people increases in relevance. With migration of people from the Arab... (Review)
Review
BACKGROUND
As population ageing takes place around the world, research on attitudes toward ageing and older people increases in relevance. With migration of people from the Arab world into countries with high percentages of older adults, attitudes toward ageing and older adults held in Arab culture are of particular interest.
OBJECTIVE
The article provides a review of the empirical literature on attitudes toward ageing and older adults held in the Arab world and discusses the findings on the basis of the general literature on age stereotypes, attitudes toward ageing, and ageism as well as their link to culture.
METHOD
A literature search was performed to find empirical studies on attitudes toward ageing and older adults that include Arab samples. Studies published in Arabic or English were included.
RESULTS
Studies on attitudes toward ageing with Arab samples are scarce and do not show cohesive patterns of results. None of the hypotheses that have been brought forward to explain cross-cultural differences regarding attitudes toward ageing (i.e., the culture, modernization, and speed of population ageing hypotheses) can fully account for the results. Possible reasons for conflicting results include sociodemographic variables, regional differences, lack of differentiation between meta-perceptions and personal attitudes, heterogeneity of measurement instruments and definitions of "older people" and possible confounds due to the usage of subjective Likert scales in cross-cultural studies.
CONCLUSION
Further research on attitudes toward ageing in Arab samples are needed and should consider heterogeneity within Arab culture as well as variables other than culture.
Topics: Aged; Aged, 80 and over; Ageism; Aging; Arabs; Attitude; Cross-Cultural Comparison; Female; Humans; Male; Stereotyping
PubMed: 31363837
DOI: 10.1007/s00391-019-01554-y -
Sub-cellular Biochemistry 2019With an increasingly ageing population that is expected to double by 2050 in the U.S., it is paramount that we further understand the neurological changes that occur... (Review)
Review
With an increasingly ageing population that is expected to double by 2050 in the U.S., it is paramount that we further understand the neurological changes that occur during ageing. This is relevant not only in the context of "pathological" ageing, where the development of many neurodegenerative disorders is typically a feature of only the older population (and indeed, age is the primary risk factor for many conditions such as Alzheimer's disease), but also for what is considered to be "normal" or "healthy" ageing. Specifically, a significant proportion of the older population are affected by "age-related cognitive decline" (ARCD), which is both independent of dementia and has an incidence 70% higher than dementia alone. However, whilst it is reported that there are pathogenic and phenotypic overlaps between healthy and pathological ageing, it is clear that there is a need to identify the pathways and understand the mechanisms that contribute to this loss of cognitive function with normal ageing, particularly in light of the increasing life expectancy of the global population. Importantly, there is an increasing body of evidence implicating zinc homeostasis as a key player in learning and memory and also potentially ARCD. Further research will ultimately contribute to the development of targeted therapeutics that will promote successful brain ageing. In this chapter we will explore the notion of ARCD, with a perspective on potential key neurochemical pathways that can be targeted for future intervention.
Topics: Aging; Alzheimer Disease; Cognition; Cognition Disorders; Humans; Zinc
PubMed: 30888651
DOI: 10.1007/978-981-13-3681-2_5 -
Epidemiology and Psychiatric Sciences Dec 2017The extension of life does not appear to be slowing, representing a great achievement for mankind as well as a challenge for ageing populations. As we move towards an...
The extension of life does not appear to be slowing, representing a great achievement for mankind as well as a challenge for ageing populations. As we move towards an increasingly older population we will need to find novel ways for individuals to make the best of the challenges they face, as the likelihood of encountering some form of adversity increases with age. Resilience theories share a common idea that individuals who manage to navigate adversity and maintain high levels of functioning demonstrate resilience. Traditional models of healthy ageing suggest that having a high level of functioning across a number of domains is a requirement. The addition of adversity to the healthy ageing model via resilience makes this concept much more accessible and more amenable to the ageing population. Through asset-based approaches, such as the invoking of individual, social and environmental resources, it is hoped that greater resilience can be fostered at a population level. Interventions aimed at fostering greater resilience may take many forms; however, there is great potential to increase social and environmental resources through public policy interventions. The wellbeing of the individual must be the focus of these efforts; quality of life is an integral component to the enjoyment of additional years and should not be overlooked. Therefore, it will become increasingly important to use resilience as a public health concept and to intervene through policy to foster greater resilience by increasing resources available to older people. Fostering wellbeing in the face of increasing adversity has significant implications for ageing individuals and society as a whole.
Topics: Adaptation, Psychological; Aged; Aging; Health Status; Healthy Aging; Humans; Male; Mental Health; Quality of Life; Resilience, Psychological; Social Support
PubMed: 28679453
DOI: 10.1017/S2045796017000324 -
International Journal of Molecular... Nov 2017DNA damage causally contributes to aging and age-related diseases. The declining functioning of tissues and organs during aging can lead to the increased risk of... (Review)
Review
DNA damage causally contributes to aging and age-related diseases. The declining functioning of tissues and organs during aging can lead to the increased risk of succumbing to aging-associated diseases. Congenital syndromes that are caused by heritable mutations in DNA repair pathways lead to cancer susceptibility and accelerated aging, thus underlining the importance of genome maintenance for withstanding aging. High-throughput mass-spectrometry-based approaches have recently contributed to identifying signalling response networks and gaining a more comprehensive understanding of the physiological adaptations occurring upon unrepaired DNA damage. The insulin-like signalling pathway has been implicated in a DNA damage response (DDR) network that includes epidermal growth factor (EGF)-, AMP-activated protein kinases (AMPK)- and the target of rapamycin (TOR)-like signalling pathways, which are known regulators of growth, metabolism, and stress responses. The same pathways, together with the autophagy-mediated proteostatic response and the decline in energy metabolism have also been found to be similarly regulated during natural aging, suggesting striking parallels in the physiological adaptation upon persistent DNA damage due to DNA repair defects and long-term low-level DNA damage accumulation occurring during natural aging. These insights will be an important starting point to study the interplay between signalling networks involved in progeroid syndromes that are caused by DNA repair deficiencies and to gain new understanding of the consequences of DNA damage in the aging process.
Topics: Adaptation, Physiological; Aging; Animals; DNA Damage; Genomic Instability; Humans; Signal Transduction
PubMed: 29113067
DOI: 10.3390/ijms18112329 -
Diabetologia Oct 2019Ageing and diabetes lead to similar organ dysfunction that is driven by parallel molecular mechanisms, one of which is cellular senescence. The abundance of senescent... (Review)
Review
Ageing and diabetes lead to similar organ dysfunction that is driven by parallel molecular mechanisms, one of which is cellular senescence. The abundance of senescent cells in various tissues increases with age, obesity and diabetes. Senescent cells have been directly implicated in the generation of insulin resistance. Recently, drugs that preferentially target senescent cells, known as senolytics, have been described and recently entered clinical trials. In this review, we explore the biological links between ageing and diabetes, specifically focusing on cellular senescence. We summarise the current data on cellular senescence in key target tissues associated with the development and clinical phenotypes of type 2 diabetes and discuss the therapeutic potential of targeting cellular senescence in diabetes.
Topics: Aging; Animals; Cellular Senescence; Diabetes Mellitus, Type 2; Humans
PubMed: 31451866
DOI: 10.1007/s00125-019-4934-x -
Nature Reviews. Endocrinology Jun 2013Secretion of growth hormone (GH), and consequently that of insulin-like growth factor 1 (IGF-1), declines over time until only low levels can be detected in individuals... (Review)
Review
Secretion of growth hormone (GH), and consequently that of insulin-like growth factor 1 (IGF-1), declines over time until only low levels can be detected in individuals aged ≥60 years. This phenomenon, which is known as the 'somatopause', has led to recombinant human GH being widely promoted and abused as an antiageing drug, despite lack of evidence of efficacy. By contrast, several mutations that decrease the tone of the GH/IGF-1 axis are associated with extended longevity in mice. In humans, corresponding or similar mutations have been identified, but whether these mutations alter longevity has yet to be established. The powerful effect of reduced GH activity on lifespan extension in mice has generated the hypothesis that pharmaceutically inhibiting, rather than increasing, GH action might delay ageing. Moreover, mice as well as humans with reduced activity of the GH/IGF-1 axis are protected from cancer and diabetes mellitus, two major ageing-related morbidities. Here, we review data on mouse strains with alterations in the GH/IGF-1 axis and their effects on lifespan. The outcome of corresponding or similar mutations in humans is described, as well as the potential mechanisms underlying increased longevity and the therapeutic benefits and risks of medical disruption of the GH/IGF-1 axis in humans.
Topics: Aging; Growth Hormone; Humans; Insulin-Like Growth Factor I; Longevity
PubMed: 23591370
DOI: 10.1038/nrendo.2013.67 -
Nature Nov 2000Living in an oxygenated environment has required the evolution of effective cellular strategies to detect and detoxify metabolites of molecular oxygen known as reactive... (Review)
Review
Living in an oxygenated environment has required the evolution of effective cellular strategies to detect and detoxify metabolites of molecular oxygen known as reactive oxygen species. Here we review evidence that the appropriate and inappropriate production of oxidants, together with the ability of organisms to respond to oxidative stress, is intricately connected to ageing and life span.
Topics: Aging; Animals; Cellular Senescence; Energy Intake; Humans; Longevity; Oxidants; Oxidative Stress; Reactive Oxygen Species; Signal Transduction
PubMed: 11089981
DOI: 10.1038/35041687 -
Molecular Neurobiology Feb 2022Cellular homeostasis is maintained by rapid and systematic cleansing of aberrant and aggregated proteins within cells. Neurodegenerative diseases (NDs) especially... (Review)
Review
Cellular homeostasis is maintained by rapid and systematic cleansing of aberrant and aggregated proteins within cells. Neurodegenerative diseases (NDs) especially Parkinson's and Alzheimer's disease are known to be associated with multiple factors, most important being impaired clearance of aggregates, resulting in the accumulation of specific aggregated protein in the brain. Protein quality control (PQC) of proteostasis network comprises proteolytic machineries and chaperones along with their regulators to ensure precise operation and maintenance of proteostasis. Such regulatory factors coordinate among each other multiple functional aspects related to proteins, including their synthesis, folding, transport, and degradation. During aging due to inevitable endogenous and external stresses, sustaining a proteome balance is a challenging task. Such stresses decline the capacity of the proteostasis network compromising the proteome integrity, affecting the fundamental physiological processes including reproductive fitness of the organism. This review focuses on highlighting proteome-wide changes during aging and the strategies for proteostasis improvements. The possibility of augmenting the proteostasis network either via genetic or pharmacological interventions may be a promising strategy towards delaying age-associated pathological consequences due to proteome disbalance, thus promoting healthy aging and prolonged longevity.
Topics: Aging; Humans; Longevity; Molecular Chaperones; Protein Folding; Proteostasis; Proteostasis Deficiencies
PubMed: 34792731
DOI: 10.1007/s12035-021-02640-2