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Cold Spring Harbor Perspectives in... Jan 2024NAD, the essential metabolite involved in multiple reactions such as the regulation of cellular metabolism, energy production, DNA repair, mitophagy and autophagy,... (Review)
Review
NAD, the essential metabolite involved in multiple reactions such as the regulation of cellular metabolism, energy production, DNA repair, mitophagy and autophagy, inflammation, and neuronal function, has been the subject of intense research in the field of aging and disease over the last decade. NAD levels decline with aging and in some age-related diseases, and reduction in NAD affects all the hallmarks of aging. Here, we present an overview of the discovery of NAD, the cellular pathways of producing and consuming NAD, and discuss how imbalances in the production rate and cellular request of NAD likely contribute to aging and age-related diseases including neurodegeneration. Preclinical studies have revealed great potential for NAD precursors in promotion of healthy aging and improvement of neurodegeneration. This has led to the initiation of several clinical trials with NAD precursors to treat accelerated aging, age-associated dysfunctions, and diseases including Alzheimer's and Parkinson's. NAD supplementation has great future potential clinically, and these studies will also provide insight into the mechanisms of aging.
Topics: Humans; NAD; Aging; Cognition; Neurons; Autophagy
PubMed: 37848251
DOI: 10.1101/cshperspect.a041193 -
Biomedical Journal Apr 2024Senescence is a condition of cell cycle arrest that increases inflammation and contributes to the development of chronic diseases in the aging human body. While several... (Review)
Review
Senescence is a condition of cell cycle arrest that increases inflammation and contributes to the development of chronic diseases in the aging human body. While several compounds described as senolytics and senomorphics produce health benefits by reducing the burden of senescence, less attention has been devoted to lifestyle interventions that produce similar effects. We describe here the effects of exercise, nutrition, caloric restriction, intermittent fasting, phytochemicals from natural products, prebiotics and probiotics, and adequate sleep on senescence in model organisms and humans. These interventions can be integrated within a healthy lifestyle to reduce senescence and inflammation and delay the consequences of aging.
Topics: Humans; Aging; Life Style; Exercise; Caloric Restriction; Cellular Senescence; Animals
PubMed: 37925155
DOI: 10.1016/j.bj.2023.100676 -
Biogerontology Apr 2024Improving human healthspan in our rapidly aging population has never been more imperative. Telomeres, protective "caps" at the ends of linear chromosomes, are essential... (Review)
Review
Improving human healthspan in our rapidly aging population has never been more imperative. Telomeres, protective "caps" at the ends of linear chromosomes, are essential for maintaining genome stability of eukaryotic genomes. Due to their physical location and the "end-replication problem" first envisioned by Dr. Alexey Olovnikov, telomeres shorten with cell division, the implications of which are remarkably profound. Telomeres are hallmarks and molecular drivers of aging, as well as fundamental integrating components of the cumulative effects of genetic, lifestyle, and environmental factors that erode telomere length over time. Ongoing telomere attrition and the resulting limit to replicative potential imposed by cellular senescence serves a powerful tumor suppressor function, and also underlies aging and a spectrum of age-related degenerative pathologies, including reduced fertility, dementias, cardiovascular disease and cancer. However, very little data exists regarding the extraordinary stressors and exposures associated with long-duration space exploration and eventual habitation of other planets, nor how such missions will influence telomeres, reproduction, health, disease risk, and aging. Here, we briefly review our current understanding, which has advanced significantly in recent years as a result of the NASA Twins Study, the most comprehensive evaluation of human health effects associated with spaceflight ever conducted. Thus, the Twins Study is at the forefront of personalized space medicine approaches for astronauts and sets the stage for subsequent missions. We also extrapolate from current understanding to future missions, highlighting potential biological and biochemical strategies that may enable human survival, and consider the prospect of longevity in the extreme environment of space.
Topics: Humans; Aging; Cellular Senescence; Longevity; Planets; Telomere; Twin Studies as Topic
PubMed: 38581556
DOI: 10.1007/s10522-024-10098-7 -
Ageing Research Reviews Nov 2023This commentary provides a novel synthesis of how biological systems adapt to a broad spectrum of environmental and age-related stresses that are underlying causes of... (Review)
Review
This commentary provides a novel synthesis of how biological systems adapt to a broad spectrum of environmental and age-related stresses that are underlying causes of numerous degenerative diseases and debilitating effects of aging. It proposes that the most fundamental, evolutionary-based integrative strategy to sustain and protect health is based on the concept of hormesis. This concept integrates anti-oxidant, anti-inflammatory and cellular repair responses at all levels of biological organization (i.e., cell, organ and organism) within the framework of biphasic dose responses that describe the quantitative limits of biological plasticity in all cells and organisms from bacteria and plants to humans. A major feature of the hormetic concept is that low levels of biological, chemical, physical and psychological stress upregulate adaptive responses that not only precondition, repair and restore normal functions to damaged tissues/organs but modestly overcompensate, reducing ongoing background damage, thereby enhancing health beyond that in control groups, lacking the low level "beneficial" stress. Higher doses of such stress often become counterproductive and eventually harmful. Hormesis is active throughout the life-cycle and can be diminished by aging processes affecting the onset and severity of debilitating conditions/diseases, especially in elderly subjects. The most significant feature of the hormetic dose response is that the limits of biological plasticity for adaptive processes are less than twice that of control group responses, with most, at maximum, being 30-60 % greater than control group values. Yet, these modest increases can make the difference between health or disease and living or dying. The quantitative features of these adaptive hormetic dose responses are also independent of mechanism. These features of the hormetic dose response determine the capacity to which systems can adapt/be protected, the extent to which biological performance (e.g., memory, resistance to injury/disease, wound healing, hair growth or lifespan) can be enhanced/extended and the extent to which synergistic interactions may occur. Hormesis defines the quantitative rules within which adaptive processes operate and is central to evolution and biology and should become transformational for experimental concepts and study design strategies, public health practices and a vast range of therapeutic strategies and interventions.
Topics: Humans; Aged; Hormesis; Longevity; Aging; Adaptation, Physiological; Antioxidants
PubMed: 37709054
DOI: 10.1016/j.arr.2023.102074 -
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 -
Ageing Research Reviews Jul 2023Aging represents the major risk factor for the onset and/or progression of various disorders including neurodegenerative diseases, metabolic disorders, and bone-related... (Review)
Review
Aging represents the major risk factor for the onset and/or progression of various disorders including neurodegenerative diseases, metabolic disorders, and bone-related defects. As the average age of the population is predicted to exponentially increase in the coming years, understanding the molecular mechanisms underlying the development of aging-related diseases and the discovery of new therapeutic approaches remain pivotal. Well-reported hallmarks of aging are cellular senescence, genome instability, autophagy impairment, mitochondria dysfunction, dysbiosis, telomere attrition, metabolic dysregulation, epigenetic alterations, low-grade chronic inflammation, stem cell exhaustion, altered cell-to-cell communication and impaired proteostasis. With few exceptions, however, many of the molecular players implicated within these processes as well as their role in disease development remain largely unknown. RNA binding proteins (RBPs) are known to regulate gene expression by dictating at post-transcriptional level the fate of nascent transcripts. Their activity ranges from directing primary mRNA maturation and trafficking to modulation of transcript stability and/or translation. Accumulating evidence has shown that RBPs are emerging as key regulators of aging and aging-related diseases, with the potential to become new diagnostic and therapeutic tools to prevent or delay aging processes. In this review, we summarize the role of RBPs in promoting cellular senescence and we highlight their dysregulation in the pathogenesis and progression of the main aging-related diseases, with the aim of encouraging further investigations that will help to better disclose this novel and captivating molecular scenario.
Topics: Humans; Aging; Cellular Senescence; Metabolic Diseases; Neurodegenerative Diseases; RNA-Binding Proteins
PubMed: 37211318
DOI: 10.1016/j.arr.2023.101958 -
Nature Reviews. Nephrology May 2024Sirtuins (SIRTs) are putative regulators of lifespan in model organisms. Since the initial discovery that SIRTs could promote longevity in nematodes and flies, the... (Review)
Review
Sirtuins (SIRTs) are putative regulators of lifespan in model organisms. Since the initial discovery that SIRTs could promote longevity in nematodes and flies, the identification of additional properties of these proteins has led to understanding of their roles as exquisite sensors that link metabolic activity to oxidative states. SIRTs have major roles in biological processes that are important in kidney development and physiological functions, including mitochondrial metabolism, oxidative stress, autophagy, DNA repair and inflammation. Furthermore, altered SIRT activity has been implicated in the pathophysiology and progression of acute and chronic kidney diseases, including acute kidney injury, diabetic kidney disease, chronic kidney disease, polycystic kidney disease, autoimmune diseases and renal ageing. The renoprotective roles of SIRTs in these diseases make them attractive therapeutic targets. A number of SIRT-activating compounds have shown beneficial effects in kidney disease models; however, further research is needed to identify novel SIRT-targeting strategies with the potential to treat and/or prevent the progression of kidney diseases and increase the average human healthspan.
Topics: Sirtuins; Humans; Kidney Diseases; Animals; Kidney; Oxidative Stress; Renal Insufficiency, Chronic; Mitochondria; Aging; Autophagy
PubMed: 38321168
DOI: 10.1038/s41581-024-00806-4 -
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 -
Tidsskrift For Den Norske Laegeforening... Jan 2024In ectropion, the eyelid margin - typically the lower eyelid - is turned outward. This condition is becoming increasingly common due to the ageing population. Ectropion... (Review)
Review
In ectropion, the eyelid margin - typically the lower eyelid - is turned outward. This condition is becoming increasingly common due to the ageing population. Ectropion is classified as either acquired or congenital, with the former being the most prevalent. Acquired ectropion is further divided into involutional, paralytic, mechanical and cicatricial subtypes. Involutional ectropion is the most common where there is no patient population bias. This clinical review provides an overview of ectropion.
Topics: Humans; Aging; Ectropion
PubMed: 38258716
DOI: 10.4045/tidsskr.23.0309 -
Biogerontology Dec 2023Human ageing is a complex, multifactorial process characterised by physiological damage, increased risk of age-related diseases and inevitable functional deterioration.... (Review)
Review
Human ageing is a complex, multifactorial process characterised by physiological damage, increased risk of age-related diseases and inevitable functional deterioration. As the population of the world grows older, placing significant strain on social and healthcare resources, there is a growing need to identify reliable and easy-to-employ markers of healthy ageing for early detection of ageing trajectories and disease risk. Such markers would allow for the targeted implementation of strategies or treatments that can lessen suffering, disability, and dependence in old age. In this review, we summarise the healthy ageing scores reported in the literature, with a focus on the past 5 years, and compare and contrast the variables employed. The use of approaches to determine biological age, molecular biomarkers, ageing trajectories, and multi-omics ageing scores are reviewed. We conclude that the ideal healthy ageing score is multisystemic and able to encompass all of the potential alterations associated with ageing. It should also be longitudinal and able to accurately predict ageing complications at an early stage in order to maximize the chances of successful early intervention.
Topics: Humans; Healthy Aging; Aging; Biomarkers
PubMed: 37439885
DOI: 10.1007/s10522-023-10041-2