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Mechanisms of Ageing and Development Dec 2023The naked mole-rat (NMR) Heterocephalus glaber (from the Greek/latin words ἕτερος, heteros = divergent, κεφαλή, kephalē = head and glabra = hairless) was... (Review)
Review
The naked mole-rat (NMR) Heterocephalus glaber (from the Greek/latin words ἕτερος, heteros = divergent, κεφαλή, kephalē = head and glabra = hairless) was first described by Rüppell (Fig. 1) and belongs to the Hystricognath (from the Greek words ὕστριξ, hystrix = porcupine and γνάθος, gnathos = jaw) as a suborder of rodents. NMR are characterized by the highest longevity among rodents and reveal a profound cancer resistance. Details of its skin-specific protective and resistance mechanisms against aging and carcinogenesis have so far not been adequately characterized. Recently, our knowledge of NMR skin biology was complemented and expanded by published data using state-of-the art histological and molecular techniques. Here we review and integrate novel published data regarding skin morphology and histology of the aging NMR and the underlying mechanisms at the cellular and molecular level. We relate this data to the longevity of the NMR and its resistance to neoplastic transformation and discuss further open questions to understand its extraordinary longevity. In addition, we will address the exposome, defined as "the total of all non-genetic, endogenous and exogenous environmental influences" on the skin, respiratory tract, stomach, and intestine. Finally, we will discuss in perspective further intriguing possibilities arising from the interaction of skin with other organs.
Topics: Animals; Resilience, Psychological; Aging; Longevity; Neoplasms; Mole Rats
PubMed: 37993056
DOI: 10.1016/j.mad.2023.111887 -
International Journal of Molecular... Jul 2023Ageing constitutes the biggest risk factor for poor health and adversely affects the integrity and function of all the cells, tissues, and organs in the human body.... (Review)
Review
Ageing constitutes the biggest risk factor for poor health and adversely affects the integrity and function of all the cells, tissues, and organs in the human body. Vascular ageing, characterised by vascular stiffness, endothelial dysfunction, increased oxidative stress, chronic low-grade inflammation, and early-stage atherosclerosis, may trigger or exacerbate the development of age-related vascular diseases, which each year contribute to more than 3.8 million deaths in Europe alone and necessitate a better understanding of the mechanisms involved. To this end, a large number of recent preclinical and clinical studies have focused on the exponential accumulation of senescent cells in the vascular system and paid particular attention to the specific roles of senescence-associated secretory phenotype, proteostasis dysfunction, age-mediated modulation of certain microRNA (miRNAs), and the contribution of other major vascular risk factors, notably diabetes, hypertension, or smoking, to vascular ageing in the elderly. The data generated paved the way for the development of various senotherapeutic interventions, ranging from the application of synthetic or natural senolytics and senomorphics to attempt to modify lifestyle, control diet, and restrict calorie intake. However, specific guidelines, considering the severity and characteristics of vascular ageing, need to be established before widespread use of these agents. This review briefly discusses the molecular and cellular mechanisms of vascular ageing and summarises the efficacy of widely studied senotherapeutics in the context of vascular ageing.
Topics: Humans; Aged; Cellular Senescence; Aging; Risk Factors; Hypertension; MicroRNAs
PubMed: 37511296
DOI: 10.3390/ijms241411538 -
Sensors (Basel, Switzerland) Dec 2023This review outlines the latest methods and innovations for assessing arterial stiffness, along with their respective advantages and disadvantages. Furthermore, we... (Review)
Review
This review outlines the latest methods and innovations for assessing arterial stiffness, along with their respective advantages and disadvantages. Furthermore, we present compelling evidence indicating a recent growth in research focused on assessing arterial stiffness using photoplethysmography (PPG) and propose PPG as a potential tool for assessing vascular ageing in the future. Blood vessels deteriorate with age, losing elasticity and forming deposits. This raises the likelihood of developing cardiovascular disease (CVD), widely reported as the global leading cause of death. The ageing process induces structural modifications in the vascular system, such as increased arterial stiffness, which can cause various volumetric, mechanical, and haemodynamic alterations. Numerous techniques have been investigated to assess arterial stiffness, some of which are currently used in commercial medical devices and some, such as PPG, of which still remain in the research space.
Topics: Humans; Photoplethysmography; Vascular Stiffness; Cardiovascular Diseases; Aging; Arteries
PubMed: 38139728
DOI: 10.3390/s23249882 -
Ageing Research Reviews Jun 2024Cellular senescence is a kind of cellular state triggered by endogenous or exogenous stimuli, which is mainly characterized by stable cell cycle arrest and complex... (Review)
Review
Cellular senescence is a kind of cellular state triggered by endogenous or exogenous stimuli, which is mainly characterized by stable cell cycle arrest and complex senescence-associated secretory phenotype (SASP). Once senescent cells accumulate in tissues, they may eventually accelerate the progression of age-related diseases, such as atherosclerosis, osteoarthritis, chronic lung diseases, cancers, etc. Recent studies have shown that the disorders of lipid metabolism are not only related to age-related diseases, but also regulate the cellular senescence process. Based on existing research evidences, the changes in lipid metabolism in senescent cells are mainly concentrated in the metabolic processes of phospholipids, fatty acids and cholesterol. Obviously, the changes in lipid-metabolizing enzymes and proteins involved in these pathways play a critical role in senescence. However, the link between cellular senescence, changes in lipid metabolism and age-related disease remains to be elucidated. Herein, we summarize the lipid metabolism changes in senescent cells, especially the senescent cells that promote age-related diseases, as well as focusing on the role of lipid-related enzymes or proteins in senescence. Finally, we explore the prospect of lipids in cellular senescence and their potential as drug targets for preventing and delaying age-related diseases.
Topics: Humans; Cellular Senescence; Lipid Metabolism; Aging; Animals; Lipids
PubMed: 38583577
DOI: 10.1016/j.arr.2024.102294 -
GeroScience Dec 2023The degenerative processes that occur during aging increase the risk of disease and impaired health. Meanwhile, interventions that target aging to promote healthy...
The degenerative processes that occur during aging increase the risk of disease and impaired health. Meanwhile, interventions that target aging to promote healthy longevity are gaining interest, both academically and in the public. While nutritional and physical interventions exist, efficacy is often difficult to determine. It is therefore imperative that an aging score measuring the biological aging process is available to the wider public. However, simple, interpret, and accessible biological aging scores are lacking. Here, we developed PhysiAge, a physiological aging score based on five accessible parameters that have influence on or reflect the aging process: (1) average daily step count, (2) blood glucose, (3) systolic blood pressure, (4) sex, and (5) age. Here, we found that compared to calendar age alone, PhysiAge better predicts mortality, as well as established muscle aging markers such as decrease in NAD levels, increase in oxidative stress, and decline in physical functioning. In order to demonstrate the usefulness of PhysiAge in identifying relevant factors associated with decelerated aging, we calculated PhysiAges for a cohort of aged individuals and obtained mass spectrometry-based blood plasma metabolomic profiles for each individual. Here, we identified a metabolic signature of decelerated aging, which included components of the TCA cycle, including malate, citrate, and isocitrate. Higher abundance of these metabolites was associated with decelerated aging, in line with supplementation studies in model organisms. PhysiAge represents an accessible way for people to track and intervene in their aging trajectories, and identifies a metabolic signature of decelerated aging in human blood plasma, which can be further studied for its causal involvement in human aging.
Topics: Humans; Aged; Aging; Longevity; Metabolomics; Oxidative Stress; Plasma
PubMed: 37259015
DOI: 10.1007/s11357-023-00827-0 -
Nature Reviews. Cardiology Dec 2023
Topics: Humans; Sirtuin 2; Aging; Heart
PubMed: 37853159
DOI: 10.1038/s41569-023-00950-7 -
The Gerontologist Jul 2024This essay argues for a fuller integration of ageism and age discrimination into the productive aging framework. We briefly review the productive aging scholarship and... (Review)
Review
This essay argues for a fuller integration of ageism and age discrimination into the productive aging framework. We briefly review the productive aging scholarship and the extent to which ageism has been considered in regard to working, volunteering, education, and caregiving. We suggest that ageism has not been adequately considered, and we identify how it permeates productive engagement in later life. We introduce modifications to the productive aging framework to more directly capture the roles of ageism and age discrimination in activity engagement and the outcomes achieved. We argue for the integration of key concepts from minority stress theory and critical race theory that may yield important insights for an increasingly diverse older population. We conclude with research directions that will guide intervention development to reduce ageism at the societal, organizational, and individual level.
Topics: Ageism; Humans; Aging; Aged; Caregivers; Employment; Volunteers
PubMed: 37974496
DOI: 10.1093/geront/gnad156 -
HEC Forum : An Interdisciplinary... Jun 2024John Davis (New Methuselahs: The Ethics of Life Extension, The MIT Press, Cambridge, 2018) advances a novel ethical analysis of longevity science that employs a...
John Davis (New Methuselahs: The Ethics of Life Extension, The MIT Press, Cambridge, 2018) advances a novel ethical analysis of longevity science that employs a three-fold methodology of examining the impact of life extension technologies on three distinct groups: the "Haves", the "Have-nots" and the "Will-nots". In this essay, I critically examine the egalitarian analysis Davis deploys with respect to its ability to help us theorize about the moral significance of an applied gerontological intervention. Rather than focusing on futuristic scenarios of radical life extension, I offer a rival egalitarian analysis that takes seriously (1) the health vulnerabilities of today's aging populations, (2) the health inequalities of the "aging status quo" and, (3) the prospects for the fair diffusion of an aging intervention over the not-so-distant future. Despite my reservations about Davis's focus on "life-extension" vs. increasing the human "healthspan", I agree with his central conclusion that an aging intervention would be, on balance, a good thing and that we should fund such research aggressively. But, I make an even stronger case and conjecture that an intervention that slows down the rate of molecular and cellular decline from the inborn aging process will likely be one of the most important public health advancements of the twenty-first century. This is so because aging is the most prevalent risk factor for chronic disease, frailty and disability, and it is estimated that there will be over 2 billion persons age > 60 by the year 2050.
Topics: Humans; Aging; Longevity; Life Expectancy
PubMed: 36348214
DOI: 10.1007/s10730-022-09499-3 -
Ageing Research Reviews Sep 2023A recent call was made for autonomic nervous system (ANS) measures as digital health markers for early detection of Alzheimer's disease and related dementia (AD/ADRD).... (Review)
Review
A recent call was made for autonomic nervous system (ANS) measures as digital health markers for early detection of Alzheimer's disease and related dementia (AD/ADRD). Nevertheless, contradictory or inconclusive findings exist. To help advance understanding of ANS' role in dementia, we draw upon aging and dementia-related literature, and propose a framework that centers on the role of ANS flexibility to guide future work on application of ANS function to differentiating the degree and type of dementia-related brain pathologies. We first provide a brief review of literature within the past 10 years on ANS and dementia-related brain pathologies. Next, we present an ANS flexibility model, describing how the model can be applied to understand these brain pathologies, as well as differentiate or even be leveraged to modify typical brain aging and dementia. Lastly, we briefly discuss the implication of the model for understanding resilience and vulnerability to dementia-related outcomes.
Topics: Humans; Brain; Autonomic Nervous System; Alzheimer Disease; Aging
PubMed: 37459967
DOI: 10.1016/j.arr.2023.102016 -
Neuroscience and Biobehavioral Reviews Oct 2023Chronic stress is a risk factor for numerous aging-related diseases and has been shown to shorten lifespan in humans and other social mammals. Yet how life stress causes... (Review)
Review
Chronic stress is a risk factor for numerous aging-related diseases and has been shown to shorten lifespan in humans and other social mammals. Yet how life stress causes such a vast range of diseases is still largely unclear. In recent years, the impact of stress on health and aging has been increasingly associated with the dysregulation of the so-called hallmarks of aging. These are basic biological mechanisms that influence intrinsic cellular functions and whose alteration can lead to accelerated aging. Here, we review correlational and experimental literature (primarily focusing on evidence from humans and murine models) on the contribution of life stress - particularly stress derived from adverse social environments - to trigger hallmarks of aging, including cellular senescence, sterile inflammation, telomere shortening, production of reactive oxygen species, DNA damage, and epigenetic changes. We also evaluate the validity of stress-induced senescence and accelerated aging as an etiopathological proposition. Finally, we highlight current gaps of knowledge and future directions for the field, and discuss perspectives for translational geroscience.
Topics: Humans; Animals; Mice; Aging; Cellular Senescence; Telomere Shortening; Epigenesis, Genetic; Stress, Psychological; Mammals
PubMed: 37586578
DOI: 10.1016/j.neubiorev.2023.105359