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Nature Sep 2018Longer human lives have led to a global burden of late-life disease. However, some older people experience little ill health, a trait that should be extended to the... (Review)
Review
Longer human lives have led to a global burden of late-life disease. However, some older people experience little ill health, a trait that should be extended to the general population. Interventions into lifestyle, including increased exercise and reduction in food intake and obesity, can help to maintain healthspan. Altered gut microbiota, removal of senescent cells, blood factors obtained from young individuals and drugs can all improve late-life health in animals. Application to humans will require better biomarkers of disease risk and responses to interventions, closer alignment of work in animals and humans, and increased use of electronic health records, biobank resources and cohort studies.
Topics: Aged; Aging; Animals; Biomarkers; Cellular Senescence; Disabled Persons; Electronic Health Records; Genome-Wide Association Study; Humans; Internationality; Life Style; Longevity; Models, Animal; Netherlands; Phenotype
PubMed: 30185958
DOI: 10.1038/s41586-018-0457-8 -
The Lancet. Neurology Nov 2012The concept of cognitive reserve provides an explanation for differences between individuals in susceptibility to age-related brain changes or pathology related to... (Review)
Review
The concept of cognitive reserve provides an explanation for differences between individuals in susceptibility to age-related brain changes or pathology related to Alzheimer's disease, whereby some people can tolerate more of these changes than others and maintain function. Epidemiological studies suggest that lifelong experiences, including educational and occupational attainment, and leisure activities in later life, can increase this reserve. For example, the risk of developing Alzheimer's disease is reduced in individuals with higher educational or occupational attainment. Reserve can conveniently be divided into two types: brain reserve, which refers to differences in the brain structure that may increase tolerance to pathology, and cognitive reserve, which refers to differences between individuals in how tasks are performed that might enable some people to be more resilient to brain changes than others. Greater understanding of the concept of cognitive reserve could lead to interventions to slow cognitive ageing or reduce the risk of dementia.
Topics: Aging; Alzheimer Disease; Animals; Cognitive Reserve; Humans
PubMed: 23079557
DOI: 10.1016/S1474-4422(12)70191-6 -
Mechanisms of Ageing and Development Dec 2017MicroRNAs (miRNAs) are short, non-coding RNAs that regulate the expression of mRNA targets and play a part in the post-transcriptional silencing. To date, the prominent... (Review)
Review
MicroRNAs (miRNAs) are short, non-coding RNAs that regulate the expression of mRNA targets and play a part in the post-transcriptional silencing. To date, the prominent roles of miRNAs in stem cells have been investigated in a wide range of biological processes, including self-renewal, differentiation and proliferation. In this commentary, we first demonstrate the causes and mechanisms of somatic stem cell aging in a new aspect of miRNAs. The functions of stem cells decline with age in diverse tissues due to cellular damages and congenital disorders. The somatic stem cells exhibit type-specific phenotypes with cellular senescence during the aging process. We explore the specific miRNAs regulating stem cell aging and age-related diseases. The functional investigations of the miRNAs in somatic stem cells and degenerative diseases might facilitate the translation of knowledge into clinical practice for the regulation of stem cell aging and aging-related diseases.
Topics: Age Factors; Aging; Animals; Cell Differentiation; Cell Lineage; Cellular Senescence; Disease; Gene Expression Regulation; Humans; MicroRNAs; Phenotype; Signal Transduction; Stem Cells
PubMed: 28847486
DOI: 10.1016/j.mad.2017.08.013 -
Yi Chuan = Hereditas Jun 2021With the increase of life expectancy, the world's population is aging rapidly. Previous work in the field of aging greatly increases our understanding of biological... (Review)
Review
With the increase of life expectancy, the world's population is aging rapidly. Previous work in the field of aging greatly increases our understanding of biological mechanisms underlying longevity. Researchers have unraveled a number of longevity pathways conserved from yeast to mammals. However, recent evidence shows that mechanisms regulating the life span and those regulating age-related behavioral decline could be dissociated. The regulatory mechanisms underlying behavioral and cognitive aging is largely unknown. Previous work has described a significant age-related decline in cognitive behaviors including episodic memory, working memory, processing speed, as well as motor function deterioration and circadian dysfunction. With the advance of neuroscience and technology, more and more studies have focused on the age-related changes in structure and function of the brain. In this review, we briefly describe the deterioration of cognitive function and other behaviors in the aging process, and survey the role of age-related changes in brain structure and network, neuron morphology and function, transcriptome in brain and some conserved biological pathways on age-related cognitive and behavioral decline. Further studies on the mechanisms underpinning age-related cognitive and behavioral decline may provide clues not only for improving the quality of life for the ageing population, but also for developing intervention approaches for neurodegenerative diseases.
Topics: Aging; Animals; Cognition; Cognitive Aging; Longevity; Quality of Life
PubMed: 34284987
DOI: 10.16288/j.yczz.21-060 -
Nature Reviews. Drug Discovery Oct 2017Chronological age represents the single greatest risk factor for human disease. One plausible explanation for this correlation is that mechanisms that drive ageing might... (Review)
Review
Chronological age represents the single greatest risk factor for human disease. One plausible explanation for this correlation is that mechanisms that drive ageing might also promote age-related diseases. Cellular senescence, which is a permanent state of cell cycle arrest induced by cellular stress, has recently emerged as a fundamental ageing mechanism that also contributes to diseases of late life, including cancer, atherosclerosis and osteoarthritis. Therapeutic strategies that safely interfere with the detrimental effects of cellular senescence, such as the selective elimination of senescent cells (SNCs) or the disruption of the SNC secretome, are gaining significant attention, with several programmes now nearing human clinical studies.
Topics: Aging; Animals; Atherosclerosis; Cell Cycle Checkpoints; Cell Proliferation; Cellular Senescence; Humans; Neoplasms
PubMed: 28729727
DOI: 10.1038/nrd.2017.116 -
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 -
The Journal of Physiology Apr 2016Age is one of the major risk factors associated with cardiovascular disease (CVD). About one-fifth of the world population will be aged 65 or older by 2030, with an... (Review)
Review
Age is one of the major risk factors associated with cardiovascular disease (CVD). About one-fifth of the world population will be aged 65 or older by 2030, with an exponential increase in CVD prevalence. It is well established that environmental factors (overnutrition, smoking, pollution, sedentary lifestyles) may lead to premature defects in mitochondrial functionality, insulin signalling, endothelial homeostasis and redox balance, fostering early senescent features. Over the last few years, molecular investigations have unveiled common signalling networks which may link the ageing process with deterioration of cardiovascular homeostasis and metabolic disturbances, namely insulin resistance. These different processes seem to be highly interconnected and their interplay may favour adverse vascular and cardiac phenotypes responsible for myocardial infarction, stroke and heart failure. In the present review, we carefully describe novel molecular cues underpinning ageing, metabolism and CVD. In particular, we describe a dynamic interplay between emerging pathways such as FOXOs, AMPK, SIRT1, p66(Shc) , JunD and NF-kB. This overview will provide the background for attractive molecular targets to prevent age-driven pathology in the vasculature and the heart.
Topics: Aging; Animals; Cardiovascular Diseases; Cardiovascular System; Gene Expression Regulation, Developmental; Humans; Signal Transduction
PubMed: 26391109
DOI: 10.1113/JP270538 -
Aging Cell Dec 2020The idea that senescent cells are causally involved in aging has gained strong support from findings that the removal of such cells alleviates many age-related diseases... (Review)
Review
The idea that senescent cells are causally involved in aging has gained strong support from findings that the removal of such cells alleviates many age-related diseases and extends the life span of mice. While efforts proceed to make therapeutic use of such discoveries, it is important to ask what evolutionary forces might have been behind the emergence of cellular senescence, in order better to understand the biology that we might seek to alter. Cellular senescence is often regarded as an anti-cancer mechanism, since it limits the division potential of cells. However, many studies have shown that senescent cells often also have carcinogenic properties. This is difficult to reconcile with the simple idea of an anti-cancer mechanism. Furthermore, other studies have shown that cellular senescence is involved in wound healing and tissue repair. Here, we bring these findings and ideas together and discuss the possibility that these functions might be the main reason for the evolution of cellular senescence. Furthermore, we discuss the idea that senescent cells might accumulate with age because the immune system had to strike a balance between false negatives (overlooking some senescent cells) and false positives (destroying healthy body cells).
Topics: Aging; Animals; Biological Evolution; Carcinogenesis; Cellular Senescence; Humans; Longevity; Mice; Models, Biological; Neoplasms; Wound Healing
PubMed: 33166065
DOI: 10.1111/acel.13270 -
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 -
Sub-cellular Biochemistry 2019The skin provides the primary protection for the body against external injuries and is essential in the maintenance of general homeostasis. During ageing, resident cells... (Review)
Review
The skin provides the primary protection for the body against external injuries and is essential in the maintenance of general homeostasis. During ageing, resident cells become senescent and the extracellular matrix, mainly in the dermis, is progressively damaged affecting the normal organization of the skin and its capacity for repair. In parallel, extrinsic factors such as ultraviolet irradiation, pollution, and intrinsic factors such as diabetes or vascular disease can further accelerate this phenomenon. Indeed, numerous mechanisms are involved in age-induced degradation of the skin and these also relate to non-healing or chronic wounds in the elderly. In particular, the generation of reactive oxygen species seems to play a major role in age-related skin modifications. Certainly, targeting both the hormonal status of the skin or its surface nutrition can slow down age-induced degradation of the skin and improve healing of skin damage in the elderly. Skin care regimens that prevent radiation and pollution damage, and reinforce the skin surface and its microbiota are among the different approaches able to minimize the effects of ageing on the skin.
Topics: Aging; Extracellular Matrix; Humans; Skin; Skin Aging; Skin Care; Ultraviolet Rays
PubMed: 30888656
DOI: 10.1007/978-981-13-3681-2_10