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1.
Nat Commun ; 15(1): 1429, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365899

RESUMO

Senescence of vascular smooth muscle cells (VSMCs) contributes to aging-related cardiovascular diseases by promoting arterial remodelling and stiffness. Ferroptosis is a novel type of regulated cell death associated with lipid oxidation. Here, we show that pro-ferroptosis signaling drives VSMCs senescence to accelerate vascular NAD+ loss, remodelling and aging. Pro-ferroptotic signaling is triggered in senescent VSMCs and arteries of aged mice. Furthermore, the activation of pro-ferroptotic signaling in VSMCs not only induces NAD+ loss and senescence but also promotes the release of a pro-senescent secretome. Pharmacological or genetic inhibition of pro-ferroptosis signaling, ameliorates VSMCs senescence, reduces vascular stiffness and retards the progression of abdominal aortic aneurysm in mice. Mechanistically, we revealed that inhibition of pro-ferroptotic signaling facilitates the nuclear-cytoplasmic shuttling of proliferator-activated receptor-γ and, thereby impeding nuclear receptor coactivator 4-ferrtin complex-centric ferritinophagy. Finally, the activated pro-ferroptotic signaling correlates with arterial stiffness in a human proof-of-concept study. These findings have significant implications for future therapeutic strategies aiming to eliminate vascular ferroptosis in senescence- or aging-associated cardiovascular diseases.


Assuntos
Doenças Cardiovasculares , Músculo Liso Vascular , Humanos , Animais , Camundongos , Senescência Celular/genética , Doenças Cardiovasculares/metabolismo , NAD/metabolismo , Células Cultivadas , Envelhecimento/fisiologia , Artérias , Miócitos de Músculo Liso/metabolismo
2.
Physiol Rep ; 12(3): e15929, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38307709

RESUMO

Diastolic dysfunction is a major cardiac dysfunction, and an important predisposing factor is age. Although exercise training is often used for the prevention and treatment of cardiovascular disease nowadays, little is currently known about whether exercise interventions associated with the slowing of cardiac aging are related to mtp-related pathways. In the present study, the UAS/Tub-Gal4 system was used to knockdown whole-body mtp expression levels in Drosophila, which underwent 2 weeks of endurance training. By conducting different assays and quantifying different indicators, we sought to investigate the relationship between mtp, exercise, and age-related diastolic dysfunction. We found that (1) Drosophila in the mtpRNAi youth group exhibited age-related diastolic dysfunction and had a significantly shorter mean lifespan. (2) Endurance exercise could improve diastolic dysfunction and prolong lifespan in aged Drosophila. (3) Endurance exercise could increase the expression levels of apolpp and Acox3, and decrease the levels of TC, LDL-C, and TG in the aged group. In summary, aging causes age-associated diastolic dysfunction in Drosophila, and systemic knockdown of mtp causes premature age-associated diastolic dysfunction in young Drosophila. Besides, endurance exercise improves age-related diastolic dysfunction and prolongs lifespan.


Assuntos
Envelhecimento , Drosophila melanogaster , Longevidade , Resistência Física , Animais , Humanos , Envelhecimento/fisiologia , Coração/fisiologia , Resistência Física/fisiologia , Drosophila melanogaster/fisiologia
3.
Front Public Health ; 12: 1305303, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38327568

RESUMO

The use of human aging markers, which are physiological, biochemical and molecular indicators of structural or functional degeneration associated with aging, is the fundamental basis of individualized aging assessments. Identifying methods for selecting markers has become a primary and vital aspect of aging research. However, there is no clear consensus or uniform principle on the criteria for screening aging markers. Therefore, we combine previous research from our center and summarize the criteria for screening aging markers in previous population studies, which are discussed in three aspects: functional perspective, operational implementation perspective and methodological perspective. Finally, an evaluation framework has been established, and the criteria are categorized into three levels based on their importance, which can help assess the extent to which a candidate biomarker may be feasible, valid, and useful for a specific use context.


Assuntos
Envelhecimento , Projetos de Pesquisa , Humanos , Envelhecimento/fisiologia , Biomarcadores
4.
Zhonghua Jie He He Hu Xi Za Zhi ; 47(2): 178-182, 2024 Feb 12.
Artigo em Chinês | MEDLINE | ID: mdl-38309971

RESUMO

The world's population is ageing at a rate unprecedented in human history. As the number of older people increases, so does the prevalence of lung disease in the elderly, making it essential to understand the pathophysiology of elderly patients with lung disease. Age-related changes in immune system function and lung parenchyma occur throughout a person's life. Immunosenescence refers to the tendency for innate and adaptive immunity to decline in the elderly. As we age, changes in the innate and adaptive immune systems can lead to dysregulation and reduced immune function. A low-level chronic inflammatory state is known as inflamm-aging and is driven by immunosenescence. This review discusses the role of immunosenescence and inflamm-aging in pulmonary diseases such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, asthma, and lung infections. Understanding the different manifestations of lung diseases between the elderly and the young, finding new therapeutic sites, or improving clinical outcomes in hospitalized patients will provide clinicians with new ideas.


Assuntos
Imunossenescência , Pneumopatias , Humanos , Idoso , Imunidade Inata , Imunossenescência/fisiologia , Inflamação , Envelhecimento/fisiologia
5.
Methods Cell Biol ; 181: 109-125, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38302234

RESUMO

The process of senescence impairs the function of cells and can ultimately be a key factor in the development of disease. With an aging population, senescence-related diseases are increasing in prevalence. Therefore, understanding the mechanisms of cellular senescence within the central nervous system (CNS), including the retina, may yield new therapeutic pathways to slow or even prevent the development of neuro- and retinal degenerative diseases. One method of probing the changing functions of senescent retinal cells is to observe retinal microglial cells. Their morphological structure may change in response to their surrounding cellular environment. In this chapter, we show how microglial cells in the retina, which are implicated in aging and diseases of the CNS, can be identified, quantified, and classified into five distinct morphotypes using image processing and supervised machine learning algorithms. The process involves dissecting, staining, and mounting mouse retinas, before image capture via fluorescence microscopy. The resulting images can then be classified by morphotype using a support vector machine (SVM) we have recently described showing high accuracy. This SVM model uses shape metrics found to correspond with qualitative descriptions of the shape of each morphotype taken from existing literature. We encourage more objective and widespread use of methods of quantification such as this. We believe automatic delineation of the population of microglial cells in the retina, could potentially lead to their use as retinal imaging biomarkers for disease prediction in the future.


Assuntos
Microglia , Retina , Camundongos , Animais , Microglia/fisiologia , Processamento de Imagem Assistida por Computador/métodos , Envelhecimento/fisiologia , Aprendizado de Máquina Supervisionado
6.
J Frailty Aging ; 13(1): 50-56, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38305443

RESUMO

BACKGROUND: Social vulnerability interacts with frailty and influences individuals' health status. Although frailty and social vulnerability are highly predictive of adverse outcomes, their relationship with self-perceived health(SPH) has been less investigated. METHODS: Data are from the Irish Longitudinal Study on Ageing(TILDA), a population-based longitudinal study of ageing. We included 4,222 participants aged ≥50 years (age 61.4±8.5 years;women 56%) from Wave 1 (2009-2011) followed over three longitudinal waves (2012,2014-2015,2016). Participants responded to single questions with five response options to rate their 1)physical health, 2)mental health, and 3)health compared to peers. 30-item Frailty (FI) and Social Vulnerability (SVI) indices were calculated using standardised methods. Multivariable regression analyses were performed to establish the association between FI and SVI cross-sectionally and longitudinally over 6 years. RESULTS: Cross-sectionally, SVI (mean:0.40±0.08; range:0.14-0.81) and FI (mean: 0.13±0.08; range:0.10-0.58) were modestly correlated (r=0.256), and independently associated with poor physical health (SVI: OR 1.43, 95%CI 1.15-1.78; FI: OR 3.16, 95%CI 2.54-3.93), poor mental health (SVI: OR 1.65, 95%CI 1.17-2.35; FI: OR 3.64, 95%CI 2.53-5.24), and poor health compared to peers (SVI: OR 1.41,95%CI 1.06-1.89; FI: OR 3.86, 95%CI 2.9-5.14). Longitudinally, FI and SVI were independently and positively associated with poor physical health (SVI: ß 1.08, 95%CI 0.76-1.39; FI: ß 1.97, 95%CI 1.58-2.36), poor mental health (SVI: ß 1.18, 95%CI 0.86-1.5; FI: ß 1.58, 95%CI 1.2-1.97), and poor overall health compared to peers (SVI: ß 0.78, 95%CI 0.89-1.33; FI: ß 1.74, 95%CI 0.47-1.1). CONCLUSIONS: In a large cohort of community-dwelling older adults, frailty and social vulnerability were associated with poor SPH and with risk of SPH decline over six years.


Assuntos
Fragilidade , Idoso , Feminino , Humanos , Envelhecimento/fisiologia , Idoso Fragilizado/psicologia , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Nível de Saúde , Estudos Longitudinais , Vulnerabilidade Social , Masculino , Pessoa de Meia-Idade
7.
Nat Commun ; 15(1): 1041, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310113

RESUMO

Cellular senescence is a stress response with broad pathophysiological implications. Senotherapies can induce senescence to treat cancer or eliminate senescent cells to ameliorate ageing and age-related pathologies. However, the success of senotherapies is limited by the lack of reliable ways to identify senescence. Here, we use nuclear morphology features of senescent cells to devise machine-learning classifiers that accurately predict senescence induced by diverse stressors in different cell types and tissues. As a proof-of-principle, we use these senescence classifiers to characterise senolytics and to screen for drugs that selectively induce senescence in cancer cells but not normal cells. Moreover, a tissue senescence score served to assess the efficacy of senolytic drugs and identified senescence in mouse models of liver cancer initiation, ageing, and fibrosis, and in patients with fatty liver disease. Thus, senescence classifiers can help to detect pathophysiological senescence and to discover and validate potential senotherapies.


Assuntos
Envelhecimento , Senescência Celular , Animais , Camundongos , Humanos , Envelhecimento/fisiologia , Senescência Celular/fisiologia , Fibrose
8.
Neuroimage ; 288: 120532, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38331332

RESUMO

Aging is a major risk factor for neurodegenerative diseases like dementia and Alzheimer's disease. Even in non-pathological aging, decline in cognitive functioning is observed in the majority of the elderly population, necessitating the importance of studying the processes involved in healthy aging in order to identify brain biomarkers that promote the conservation of functioning. The default mode network (DMN) has been of special interest to aging research due to its vulnerability to atrophy and functional decline over the course of aging. Prior work has focused almost exclusively on functional (i.e. undirected) connectivity, yet converging findings are scarce. Therefore, we set out to use spectral dynamic causal modeling to investigate changes in the effective (i.e. directed) connectivity within the DMN and to discover changes in information flow in a sample of cognitively normal adults spanning from 48 to 89 years (n = 63). Age was associated to reduced verbal memory performance. Modeling of effective connectivity revealed a pattern of age-related downregulation of posterior DMN regions driven by inhibitory connections from the hippocampus and middle temporal gyrus. Additionally, there was an observed decline in the hippocampus' susceptibility to network inputs with age, effectively disconnecting itself from other regions. The estimated effective connectivity parameters were robust and able to predict the age in out of sample estimates in a leave-one-out cross-validation. Attained education moderated the effects of aging, largely reversing the observed pattern of inhibitory connectivity. Thus, medial prefrontal cortex, hippocampus and posterior DMN regions formed an excitatory cycle of extrinsic connections related to the interaction of age and education. This suggests a compensatory role of years of education in effective connectivity, stressing a possible target for interventions. Our findings suggest a connection to the concept of cognitive reserve, which attributes a protective effect of educational level on cognitive decline in aging (Stern, 2009).


Assuntos
Envelhecimento Saudável , Adulto , Humanos , Idoso , Rede de Modo Padrão , Imageamento por Ressonância Magnética , Envelhecimento/fisiologia , Encéfalo/patologia , Escolaridade
9.
Clin Biomech (Bristol, Avon) ; 112: 106169, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38211422

RESUMO

BACKGROUND: Falls pose a significant health risk in older adults, with stair descent falls carrying particularly severe consequences. Reduced balance control and limb support due to aging-related physiological and neuromuscular decline are critical components in increased falling risk in older adults. Understanding the age-associated abnormalities in balance control and limb support strategies during sudden forward and downward body shift could reveal potential biomechanical deficits responsible for increased falling risks in older adults. This study investigates balance regulatory responses following first-time exposure to compelled forward and downward body shift in young and older adults. METHODS: Thirteen healthy old and thirteen healthy young adults participated in this study. Participants stood on two adjacent perturbation platforms in modified tandem stance. The leading limb support surface dropped 3 in. vertically at an unknown time. The anterior margin of stability and center of mass velocity, peak vertical ground reaction forces, and leading limb ankle and knee joint angular displacement, torque, and power during the initial response phase were compared between age groups. FINDINGS: Compared to young adults, older adults showed higher center of mass velocity, lower margin of stability, peak vertical ground reaction force, peak ankle and knee joint power, and peak knee joint torque during the initial response phase. INTERPRETATIONS: The abnormalities potentially identified in our study, particularly in dynamic stability regulation, limb support force generation, and shock absorption may affect the ability to arrest the body's forward and downward motion. These deficits may contribute to an increased risk of forward falls in aging.


Assuntos
Articulação do Joelho , Joelho , Humanos , Adulto Jovem , Idoso , Fenômenos Biomecânicos , Articulação do Joelho/fisiologia , Extremidade Inferior/fisiologia , Envelhecimento/fisiologia , Equilíbrio Postural/fisiologia
10.
Ageing Res Rev ; 94: 102181, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38182079

RESUMO

This paper addresses how long lifespan can be extended via multiple interventions, such as dietary supplements [e.g., curcumin, resveratrol, sulforaphane, complex phytochemical mixtures (e.g., Moringa, Rhodiola)], pharmaceutical agents (e.g., metformin), caloric restriction, intermittent fasting, exercise and other activities. This evaluation was framed within the context of hormesis, a biphasic dose response with specific quantitative features describing the limits of biological/phenotypic plasticity for integrative biological endpoints (e.g., cell proliferation, memory, fecundity, growth, tissue repair, stem cell population expansion/differentiation, longevity). Evaluation of several hundred lifespan extending agents using yeast, nematode (Caenorhabditis elegans), multiple insect and other invertebrate and vertebrate models (e.g., fish, rodents), revealed they responded in a manner [average (mean/median) and maximum lifespans] consistent with the quantitative features [i.e., 30-60% greater at maximum (Hormesis Rule)] of the hormetic dose response. These lifespan extension features were independent of biological model, inducing agent, endpoints measured and mechanism. These findings indicate that hormesis describes the capacity to extend life via numerous agents and activities and that the magnitude of lifespan extension is modest, in the percentage, not fold, range. These findings have important implications for human aging, genetic diseases/environmental stresses and lifespan extension, as well as public health practices and long-term societal resource planning.


Assuntos
Hormese , Longevidade , Animais , Humanos , Longevidade/fisiologia , Hormese/fisiologia , Envelhecimento/fisiologia , Caenorhabditis elegans/fisiologia , Estresse Fisiológico
11.
Int J Cardiol ; 399: 131770, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38211679

RESUMO

BACKGROUND: Physical activity (PA) is associated with mortality and cardiovascular disease (CVD). However, the effect of circadian PA trajectories remains ambiguous. This study aimed to explore ideal circadian PA patterns to reduce mortality and CVD, and potential mediators. METHODS: 502,400 participants from UK Biobank were recruited between 2006 and 2010. Among them, 102,323 participants got valid continuously capturing acceleration data over 7 days by wrist-worn accelerometer. K-means cluster analysis was used to identify PA trajectories. The associations of PA with all-cause, cause-specific mortality and CVD were assessed by cox regression. A sensitivity test was also conducted, starting from the time of acceleration collection and excluding participants with corresponding disease prior to it. Furthermore, the mediation of aging and inflammation were explored. RESULTS: During a median follow-up of 12.9 years, 3482 deaths were recorded (704 were due to CVD). Five distinct PA trajectories were identified: Persistently Low, Moderate and Stable, Single Increase, Double Increase, and Vigorous patterns. Ideal PA trajectory patterns offered progressively protective benefits against all-cause, CVD caused mortality and CVD, especially in Double Increase and Vigorous patterns. Other cause-specific mortality and renal failure incidence showed similar trend. The sensitivity result was consistent. The mediating effects of phenotypic age and inflammation markers were statistically significant. CONCLUSION: Ideal PA trajectories offered protective benefits against all-cause, cause-specific mortality and CVD. The protection was associated with both intensity and circadian distribution. Double Increase and Vigorous activity patterns decreased these risks more significantly. Crucially, this protection was mediated by aging deceleration and inflammation regulation.


Assuntos
Bancos de Espécimes Biológicos , Doenças Cardiovasculares , Humanos , Causas de Morte , Desaceleração , Exercício Físico/fisiologia , Doenças Cardiovasculares/epidemiologia , Envelhecimento/fisiologia , Inflamação
12.
Neurosci Lett ; 823: 137646, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38278317

RESUMO

Recent research has underscored the influence of aging and exercise on brain function. In this study, we aimed to explore alterations in the expression of novel molecular factors and gain insight into underlying molecular mechanisms in the hippocampus of rats engaged in voluntary wheel running. We assessed the expression of aging-related genes in the hippocampus using a high-throughput whole genome DNA microarray approach in rats engaged in voluntary running for four weeks. The results indicated that compared to the control group, wheel running significantly altered the expressions of aging-related genes in the hippocampus. Functional categorization, utilizing pathway-focused gene classifications and disease state-focused gene classifications, along with Ingenuity Pathway Analysis (IPA), revealed changes in expression pattern in major categories of cell death and survival, renal necrosis/cell death, and cardiovascular disease genes. These findings suggest that exercise may mitigate the risk of age-related cognitive decline by regulating of aging-related genes in the hippocampus. Further research is warranted to elucidate the mechanisms driving changes in gene expression and to determine the long-term effects of exercise on brain function.


Assuntos
Atividade Motora , Condicionamento Físico Animal , Ratos , Animais , Hipocampo/metabolismo , Envelhecimento/fisiologia , Análise de Sequência com Séries de Oligonucleotídeos , Condicionamento Físico Animal/fisiologia
13.
J Infus Nurs ; 47(1): 49-53, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38211615

RESUMO

There is a growing body of evidence about physiological changes with age that impact fluid and electrolyte balance. It is important that infusion nurses have knowledge in managing care for geriatric patients so they can identify these changes when they are exhibited. Knowing how to minimize the effect of these changes on the health of older adults is critical. The infusion nurse with knowledge of geriatric-focused care can avoid complications and critical illness in older adults. In addition, it is important to provide specific patient education that is grounded in geriatric best practices. This information will assist older adults to better protect themselves from dehydration, kidney injury, and other complications associated with fluid balance, such as delirium. This article reviews the literature on specific changes with aging that predispose older adults to adverse complications with fluid imbalance. New technology in geriatrics that can improve management of fluid status, such as dehydration and electrolyte monitors, are also discussed. This review included searches of the Medline®/PubMed® Database using MeSH terms (National Library of Medicine). Search terms included the following: aging-biological; aging kidney; water-electrolyte imbalance; dehydration; hypo-hypernatremia; hypo-hyperkalemia; delirium; wearable technology; and hydration monitors.


Assuntos
Desidratação , Delírio , Humanos , Idoso , Desidratação/prevenção & controle , Equilíbrio Hidroeletrolítico/fisiologia , Envelhecimento/fisiologia , Delírio/prevenção & controle , Delírio/complicações
15.
Physiol Rep ; 12(1): e15917, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38225199

RESUMO

Sarcopenia is a systemic skeletal muscle disease characterized by a decline in skeletal muscle mass and function. Originally defined as an age-associated condition, sarcopenia presently also encompasses muscular atrophy due to various pathological factors, such as intensive care unit-acquired weakness, inactivity, and malnutrition. The exact pathogenesis of sarcopenia is still unknown; herein, we review the pathological roles of the neuromuscular junction and mitochondria in this condition. Sarcopenia is caused by complex and interdependent pathophysiological mechanisms, including aging, neuromuscular junction impairment, mitochondrial dysfunction, insulin resistance, lipotoxicity, endocrine factors, oxidative stress, and inflammation. Among these, neuromuscular junction instability and mitochondrial dysfunction are particularly significant. Dysfunction in neuromuscular junction can lead to muscle weakness or paralysis. Mitochondria, which are plentiful in neurons and muscle fibers, play an important role in neuromuscular junction transmission. Therefore, impairments in both mitochondria and neuromuscular junction may be one of the key pathophysiological mechanisms leading to sarcopenia. Moreover, this article explores the structural and functional alterations in the neuromuscular junction and mitochondria in sarcopenia, suggesting that a deeper understanding of these changes could provide valuable insights for the prevention or treatment of sarcopenia.


Assuntos
Doenças Mitocondriais , Sarcopenia , Humanos , Sarcopenia/patologia , Envelhecimento/fisiologia , Junção Neuromuscular/metabolismo , Estresse Oxidativo/fisiologia , Doenças Mitocondriais/metabolismo , Doenças Mitocondriais/patologia , Músculo Esquelético/metabolismo
16.
Cell Metab ; 36(1): 7-9, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38171339

RESUMO

Spinal cord-associated disorders are common in the elderly population; however, the mechanisms underlying spinal aging remain elusive. In a recent Nature paper, Sun et al. systemically analyzed aged spines in nonhuman primates and identified a new cluster of CHIT1-positive microglia that drives motor neuron senescence and subsequent spine aging.


Assuntos
Neurônios Motores , Medula Espinal , Animais , Humanos , Idoso , Envelhecimento/fisiologia , Microglia
17.
Proc Natl Acad Sci U S A ; 121(4): e2311313121, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38241436

RESUMO

Pharmacological therapies are promising interventions to slow down aging and reduce multimorbidity in the elderly. Studies in animal models are the first step toward translation of candidate molecules into human therapies, as they aim to elucidate the molecular pathways, cellular mechanisms, and tissue pathologies involved in the anti-aging effects. Trametinib, an allosteric inhibitor of MEK within the Ras/MAPK (Ras/Mitogen-Activated Protein Kinase) pathway and currently used as an anti-cancer treatment, emerged as a geroprotector candidate because it extended lifespan in the fruit fly Drosophila melanogaster. Here, we confirm that trametinib consistently and robustly extends female lifespan, and reduces intestinal stem cell (ISC) proliferation, tumor formation, tissue dysplasia, and barrier disruption in guts in aged flies. In contrast, pro-longevity effects of trametinib are weak and inconsistent in males, and it does not influence gut homeostasis. Inhibition of the Ras/MAPK pathway specifically in ISCs is sufficient to partially recapitulate the effects of trametinib. Moreover, in ISCs, trametinib decreases the activity of the RNA polymerase III (Pol III), a conserved enzyme synthesizing transfer RNAs and other short, non-coding RNAs, and whose inhibition also extends lifespan and reduces gut pathology. Finally, we show that the pro-longevity effect of trametinib in ISCs is partially mediated by Maf1, a repressor of Pol III, suggesting a life-limiting Ras/MAPK-Maf1-Pol III axis in these cells. The mechanism of action described in this work paves the way for further studies on the anti-aging effects of trametinib in mammals and shows its potential for clinical application in humans.


Assuntos
Drosophila melanogaster , Drosophila , Piridonas , Pirimidinonas , Animais , Masculino , Humanos , Feminino , Idoso , Drosophila melanogaster/genética , Envelhecimento/fisiologia , Células-Tronco/metabolismo , Mamíferos
18.
Aging Clin Exp Res ; 36(1): 6, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38280022

RESUMO

BACKGROUND: Aging is associated with a health impairment and an increase of the vulnerability of the older people. Strength training under intermittent hypoxic conditions has been shown to have therapeutic effects on individual's health. AIMS: The aim of this study was to investigate the effects of a combined intermittent hypoxia (IH) and whole-body vibration (WBV) training program on health-related outcomes in older people. METHODS: A total of 60 adults (over the age of 65) voluntarily participated in an intervention that lasted 20 weeks (three 30-min sessions per week). The participants were divided into four experimental groups subjected to different environmental conditions (IH vs normoxia) and exercise (non-exercise vs WBV). Functional fitness, body composition, metabolic parameters, inflammatory biomarkers, and bone turnover were evaluated before and after the intervention. A multifactorial ANOVA with repeated measures was performed to explore differences within and between groups. RESULTS: The results showed that IH and WBV had a positive synergistic effect on inflammatory parameters (CRP and IL-10), bone formation biomarker (PINP), and body composition (muscle and bone mass). CONCLUSION: In conclusion, a combined IH and WVB training could be a useful tool to prevent the deterioration of health-related outcomes associated with aging. Clinical trial registration NCT04281264. https://clinicaltrials.gov/ .


Assuntos
Treinamento de Força , Vibração , Humanos , Idoso , Vibração/uso terapêutico , Envelhecimento/fisiologia , Terapia por Exercício/métodos , Exercício Físico , Força Muscular/fisiologia
19.
Nat Commun ; 15(1): 775, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38278798

RESUMO

Accumulation of senescent cells with age leads to tissue dysfunction and related diseases. Their detection in vivo still constitutes a challenge in aging research. We describe the generation of a fluorogenic probe (sulfonic-Cy7Gal) based on a galactose derivative, to serve as substrate for ß-galactosidase, conjugated to a Cy7 fluorophore modified with sulfonic groups to enhance its ability to diffuse. When administered to male or female mice, ß-galactosidase cleaves the O-glycosidic bond, releasing the fluorophore that is ultimately excreted by the kidneys and can be measured in urine. The intensity of the recovered fluorophore reliably reflects an experimentally controlled load of cellular senescence and correlates with age-associated anxiety during aging and senolytic treatment. Interestingly, our findings with the probe indicate that the effects of senolysis are temporary if the treatment is discontinued. Our strategy may serve as a basis for developing fluorogenic platforms designed for easy longitudinal monitoring of enzymatic activities in biofluids.


Assuntos
Envelhecimento , Senescência Celular , Masculino , Feminino , Camundongos , Animais , Envelhecimento/fisiologia , Senescência Celular/fisiologia , beta-Galactosidase , Rim , Corantes Fluorescentes
20.
Clin Neurophysiol ; 158: 137-148, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38219403

RESUMO

OBJECTIVE: Both cognitive and primary motor networks alter with advancing age in humans. The networks activated in response to external environmental stimuli supported by theta oscillations remain less well explored. The present study aimed to characterize the effects of aging on the functional connectivity of response-related theta networks during sensorimotor tasks. METHODS: Electroencephalographic signals were recorded in young and middle-to-older age adults during three tasks performed in two modalities, auditory and visual: a simple reaction task, a Go-NoGo task, and a choice-reaction task. Response-related theta oscillations were computed. The phase-locking value (PLV) was used to analyze the spatial synchronization of primary motor and motor control theta networks. RESULTS: Performance was overall preserved in older adults. Independently of the task, aging was associated with reorganized connectivity of the contra-lateral primary motor cortex. In younger adults, it was synchronized with motor control regions (intra-hemispheric premotor/frontal and medial frontal). In older adults, it was only synchronized with intra-hemispheric sensorimotor regions. CONCLUSIONS: Motor theta networks of older adults manifest a functional decoupling between the response-generating motor cortex and motor control regions, which was not modulated by task variables. The overall preserved performance in older adults suggests that the increased connectivity within the sensorimotor network is associated with an excessive reliance on sensorimotor feedback during movement execution compensating for a deficient cognitive regulation of motor regions during sensorimotor reactions. SIGNIFICANCE: New evidence is provided for the reorganization of motor networks during sensorimotor reactions already at the transition from middle to old age.


Assuntos
Envelhecimento , Córtex Motor , Humanos , Idoso , Envelhecimento/fisiologia , Eletroencefalografia , Córtex Motor/fisiologia , Movimento/fisiologia , Imageamento por Ressonância Magnética
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