RESUMEN
We investigated the influence of the so-called bystander effect on metabolic and histopathological changes in the rat brain after fractionated spinal cord irradiation. The study was initiated with adult Wistar male rats (n = 20) at the age of 9 months. The group designated to irradiation (n = 10) and the age-matched control animals (n = 10) were subjected to an initial measurement using in vivo proton magnetic resonance spectroscopy (1H MRS) and magnetic resonance imaging (MRI). After allowing the animals to survive until 12 months, they received fractionated spinal cord irradiation with a total dose of 24 Gy administered in 3 fractions (8 Gy per fraction) once a week on the same day for 3 consecutive weeks. 1H MRS and MRI of brain metabolites were performed in the hippocampus, corpus striatum, and olfactory bulb (OB) before irradiation (9-month-old rats) and subsequently 48 h (12-month-old) and 2 months (14-month-old) after the completion of irradiation. After the animals were sacrificed at the age of 14 months, brain tissue changes were investigated in two neurogenic regions: the hippocampal dentate gyrus (DG) and the rostral migratory stream (RMS). By comparing the group of 9-month-old rats and individuals measured 48 h (at the age of 12 months) after irradiation, we found a significant decrease in the ratio of total N-acetyl aspartate to total creatine (tNAA/tCr) and gamma-aminobutyric acid to tCr (GABA/tCr) in OB and hippocampus. A significant increase in myoinositol to tCr (mIns/tCr) in the OB persisted up to 14 months of age. Proton nuclear magnetic resonance (1H NMR)-based plasma metabolomics showed a significant increase in keto acids and decreased tyrosine and tricarboxylic cycle enzymes. Morphometric analysis of neurogenic regions of 14-month-old rats showed well-preserved stem cells, neuroblasts, and increased neurodegeneration. The radiation-induced bystander effect more significantly affected metabolite concentration than the distribution of selected cell types.
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Envejecimiento , Encéfalo , Efecto Espectador , Ratas Wistar , Médula Espinal , Animales , Masculino , Ratas , Envejecimiento/efectos de la radiación , Envejecimiento/metabolismo , Envejecimiento/patología , Encéfalo/efectos de la radiación , Encéfalo/metabolismo , Efecto Espectador/efectos de la radiación , Médula Espinal/efectos de la radiación , Médula Espinal/metabolismo , Médula Espinal/patología , Imagen por Resonancia Magnética , Fraccionamiento de la Dosis de RadiaciónRESUMEN
Ionizing radiation is used to create models of accelerated aging because the processes of aging and radiation injury share common elements. In this chapter we review the biological processes of aging and the similarities and impact of ionizing radiation on those processes. The information draws on data from laboratory studies and from epidemiology studies of radiation exposure victims. The chapter reviews the effects of radiation on DNA, cells, and organs systems on aged adults. The science of aging and the effect of radiation on the aging process are areas of active research and our understanding is evolving.
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Fenómenos Biológicos , Exposición a la Radiación , Traumatismos por Radiación , Adulto , Envejecimiento/genética , Envejecimiento/efectos de la radiación , Humanos , Persona de Mediana Edad , Traumatismos por Radiación/prevención & control , Radiación IonizanteRESUMEN
The biological aging of titanium implants affects the service lifetime negatively in clinical applications, and Ultraviolet (UV) irradiation is an applicable method to overcome the biological aging. This study investigated the changes in surface characteristics and biological properties of bioactive titanium surfaces with different structure and topography after Ultraviolet C (UVC) irradiation. The bioactive titanium surfaces were prepared by anodizing (AO), sandblasting and acid-etching (SLA), acid-alkali etching (AA), alkali-heat etching (AH) methods. Samples were stored at dark for 7 weeks to simulate biological aging process and then irradiated by UVC for 2 h. The results showed that the hydroxyl groups (Ti-OH) on surfaces, which are crucial to enhance the biological properties, were easier to be generated on AO surfaces by UVC-irradiation, owing to a mixture of anatase and rutile on surfaces. UVC-irradiation had the strongest effect on AO surfaces to enhance the bioactivity in bone-like apatite deposition and better biocompatibility in mesenchymal stem cells (MSCs) attachment and proliferation. Therefore, titanium surfaces with a mixture phase of anatase and rutile have the potential to effectively utilize the benefits of UVC-irradiation to overcome the negative effects of the biological aging and have a promising clinical application prospect.
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Envejecimiento , Titanio , Rayos Ultravioleta , Envejecimiento/efectos de los fármacos , Envejecimiento/efectos de la radiación , Animales , Células Cultivadas , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Osteogénesis/efectos de la radiación , Conejos , Propiedades de SuperficieRESUMEN
BACKGROUND: Depopulation processes in Ukraine have been affected by the Chornobyl catastrophe (ChC), but therate of demographic aging of survivors remains uncertain. Although the mental health disorders of the survivors arerecognized internationally, problems of their research remain unresolved. Thus, these areas of research are relevant.Objective is to determine the rate of demographic aging of survivors of the Chornobyl NPP (ChNPP) accident and toanalyze the state of their mental health survey, outlining solutions. MATERIALS AND METHODS: Information and statistical sources for 1986-2019 of the Ministry of Health of Ukraine andthe State Statistics Service of Ukraine on the age of the ChC survivors are used. The results of previous own researchand other scientists using the data of the Clinical and Epidemiological Register (CER) of the State Institution«National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine¼(NRCRM), the State Register of ChC survivors (SRU), and the Department of Radiation Psychoneurology, Institute ofClinical Radiology, NRCRM are integrated. Theoretical, general scientific, demographic and mathematical-statisticalresearch methods and documentary analysis are used. RESULTS: It is shown that in 2018, compared to 1995, the number of the ChC survivors, who are under the supervi-sion of the Ministry of Health of Ukraine, decreased by almost 987 thousand. The part of people born from personsof the 1st-3rd accounting groups increased in the structure of survivors (from 13.1 % in 1995 to 13.6 %), and thisdecreased in persons living or lived in the territories subject to supervision (75.1 % and 63.1 %, respectively), butin evacuees and Chornobyl clean-up workers (liquidators) this did not change significantly. A high level of aging ofthe ChC survivors (except for the 4th group) is revealed: liquidators - 59.0 %; evacuees - 25.0 %, and residents ofradioactively contaminated territories (RCT) - 30.7 %. It has been proved that the countries of RCT differ signifi-cantly in the number of the ChC survivors and their structure. The increase in the post-accident period indicators ofthe level of aging and the average age of the RCT population indicates negative changes in age parameters and theneed to continue research to identify factors «responsible¼ for such changes. Long-term mental health disordersand neuropsychiatric effects in the ChC survivors have been identified - an excess of cerebrovascular pathology andneurocognitive deficits, especially in liquidators, which may indicate an accelerated aging. Radiation risks havebeen revealed for acute and chronic cerebrovascular pathology and organic mental disorders of non-psychotic andpsychotic levels. Neurophysiological and molecular-biological atypia of aging processes under an exposure to lowdoses of and low dose rate of ionizing radiation have been found. The psyche under the age of 40 years old at thetime of exposure is more vulnerable. Existing statistical and registry data underestimate the level of mental disor-ders in the population of Ukraine, including the ChC survivors by an order of magnitude. CONCLUSIONS: The ChC survivors are aging in the country. The negative tendencies in age parameters of survival indi-cate the need to continue research to identify the factors «responsible¼ for such changes. Mental health disordersand neuropsychiatric effects in the ChC survivors are underestimated. It is necessary to create a national psychiatricregistry of Ukraine and long-term (lifelong) monitoring of survivors with well-planned clinical and epidemiologicalstudies of general and mental health with reliable dosimetric support based on national registries using the latest information technologies.
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Envejecimiento/efectos de la radiación , Accidente Nuclear de Chernóbil , Encuestas Epidemiológicas/estadística & datos numéricos , Salud Mental/estadística & datos numéricos , Dosis de Radiación , Exposición a la Radiación/efectos adversos , Sobrevivientes/estadística & datos numéricos , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Factores Socioeconómicos , Encuestas y Cuestionarios , Factores de Tiempo , Ucrania/epidemiología , Adulto JovenRESUMEN
Alterations to the epigenome are a hallmark of biological aging and age-dependent patterning of the DNA methylome ("epigenetic aging") can be modeled to produce epigenetic age predictors. Rates of epigenetic aging vary amongst individuals and correlate to the onset of age-related disease and all-cause mortality. Yet, the origins of epigenetic-to-chronological age discordance are not empirically resolved. Here, we investigate the relationship between aging, DNA methylation, and environmental exposures in Japanese medaka (Oryzias latipes). We find age-associated DNA methylation patterning enriched in genomic regions of low CpG density and that, similar to mammals, most age-related changes occur during early life. We construct an epigenetic clock capable of predicting chronological age with a mean error of 61.1 days (~8.4% of average lifespan). To test the role of environmental factors in driving epigenetic age variation, we exposed medaka to chronic, environmentally relevant doses of ionizing radiation. Because most organisms share an evolutionary history with ionizing radiation, we hypothesized that exposure would reveal fundamental insights into environment-by-epigenetic aging interactions. Radiation exposure disrupted epigenetic aging by accelerating and decelerating normal age-associated patterning and was most pronounced in cytosines that were moderately associated with age. These findings empirically demonstrate the role of DNA methylation in integrating environmental factors into aging trajectories.
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Envejecimiento/efectos de la radiación , Epigénesis Genética/efectos de la radiación , Radiación Ionizante , Envejecimiento/genética , Envejecimiento/metabolismo , Animales , Relación Dosis-Respuesta en la Radiación , Epigenoma , OryziasRESUMEN
Time-restricted feeding (TRF) has recently gained interest as a potential anti-ageing treatment for organisms from Drosophila to humans1-5. TRF restricts food intake to specific hours of the day. Because TRF controls the timing of feeding, rather than nutrient or caloric content, TRF has been hypothesized to depend on circadian-regulated functions; the underlying molecular mechanisms of its effects remain unclear. Here, to exploit the genetic tools and well-characterized ageing markers of Drosophila, we developed an intermittent TRF (iTRF) dietary regimen that robustly extended fly lifespan and delayed the onset of ageing markers in the muscles and gut. We found that iTRF enhanced circadian-regulated transcription and that iTRF-mediated lifespan extension required both circadian regulation and autophagy, a conserved longevity pathway. Night-specific induction of autophagy was both necessary and sufficient to extend lifespan on an ad libitum diet and also prevented further iTRF-mediated lifespan extension. By contrast, day-specific induction of autophagy did not extend lifespan. Thus, these results identify circadian-regulated autophagy as a critical contributor to iTRF-mediated health benefits in Drosophila. Because both circadian regulation and autophagy are highly conserved processes in human ageing, this work highlights the possibility that behavioural or pharmaceutical interventions that stimulate circadian-regulated autophagy might provide people with similar health benefits, such as delayed ageing and lifespan extension.
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Autofagia/fisiología , Ritmo Circadiano/fisiología , Drosophila melanogaster/fisiología , Conducta Alimentaria/fisiología , Longevidad/fisiología , Envejecimiento/genética , Envejecimiento/efectos de la radiación , Animales , Autofagia/genética , Biomarcadores , Relojes Circadianos/efectos de la radiación , Ritmo Circadiano/genética , Ritmo Circadiano/efectos de la radiación , Oscuridad , Drosophila melanogaster/genética , Drosophila melanogaster/efectos de la radiación , Conducta Alimentaria/efectos de la radiación , Femenino , Longevidad/genética , Longevidad/efectos de la radiación , Masculino , Factores de TiempoRESUMEN
Methylene blue (MB) is a century-old medicine, a laboratory dye, and recently shown as a premier antioxidant that combats ROS-induced cellular aging in human skins. Given MB's molecular structure and light absorption properties, we hypothesize that MB has the potential to be considered as a sunscreen active for UV radiation protection. In this study, we tested the effects of MB on UVB ray-induced DNA double-strand breaks in primary human keratinocytes. We found that MB treatment reduced DNA damages caused by UVB irradiation and subsequent cell death. Next, we compared MB with Oxybenzone, which is the most commonly used chemical active ingredient in sunscreens but recently proven to be hazardous to aquatic ecosystems, in particular to coral reefs. At the same concentrations, MB showed more effective UVB absorption ability than Oxybenzone and significantly outperformed Oxybenzone in the prevention of UVB-induced DNA damage and the clearance of UVA-induced cellular ROS. Furthermore, unlike Oxybenzone, MB-containing seawater did not affect the growth of the coral species Xenia umbellata. Altogether, our study suggests that MB has the potential to be a coral reef-friendly sunscreen active ingredient that can provide broad-spectrum protection against UVA and UVB.
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Envejecimiento/efectos de los fármacos , Antozoos/efectos de los fármacos , Azul de Metileno/farmacología , Piel/efectos de los fármacos , Envejecimiento/patología , Envejecimiento/efectos de la radiación , Animales , Antioxidantes/farmacología , Benzofenonas/efectos adversos , Arrecifes de Coral , Roturas del ADN de Doble Cadena/efectos de los fármacos , Roturas del ADN de Doble Cadena/efectos de la radiación , Daño del ADN/efectos de los fármacos , Daño del ADN/efectos de la radiación , Ecosistema , Humanos , Queratinocitos/efectos de los fármacos , Queratinocitos/efectos de la radiación , Luz/efectos adversos , Azul de Metileno/química , Protección Radiológica , Piel/efectos de la radiación , Protectores Solares/efectos adversos , Rayos Ultravioleta/efectos adversosRESUMEN
As a radiation biodosimetry tool, gene expression profiling is being developed using mouse and human peripheral blood models. The impact of dose, dose-rate, and radiation quality has been studied with the goal of predicting radiological tissue injury. In this study, we determined the impact of aging on the gene expression profile of blood from mice exposed to radiation. Young (2 mo) and old (21 mo) male mice were irradiated with 4 Gy x-rays, total RNA was isolated from whole blood 24 h later, and subjected to whole genome microarray analysis. Pathway analysis of differentially expressed genes revealed young mice responded to x-ray exposure by significantly upregulating pathways involved in apoptosis and phagocytosis, a process that eliminates apoptotic cells and preserves tissue homeostasis. In contrast, the functional annotation of senescence was overrepresented among differentially expressed genes from irradiated old mice without enrichment of phagocytosis pathways. Pathways associated with hematologic malignancies were enriched in irradiated old mice compared with irradiated young mice. The fibroblast growth factor signaling pathway was underrepresented in older mice under basal conditions. Similarly, brain-related functions were underrepresented in unirradiated old mice. Thus, age-dependent gene expression differences should be considered when developing gene signatures for use in radiation biodosimetry.
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Regulación de la Expresión Génica/genética , Exposición a la Radiación , Transcriptoma/efectos de la radiación , Factores de Edad , Envejecimiento/genética , Envejecimiento/efectos de la radiación , Algoritmos , Animales , Apoptosis/genética , Apoptosis/efectos de la radiación , Recuento de Células Sanguíneas , Biología Computacional , Regulación hacia Abajo/efectos de la radiación , Masculino , Ratones Endogámicos C57BL , Análisis de Secuencia por Matrices de Oligonucleótidos , Fagocitosis/genética , Fagocitosis/efectos de la radiación , Transducción de Señal/efectos de la radiación , Regulación hacia Arriba/efectos de la radiación , Rayos XRESUMEN
The production of melanin pigments by melanocytes and their quantity, quality, and distribution play a decisive role in determining human skin, eye, and hair color, and protect the skin from adverse effects of ultraviolet radiation (UVR) and oxidative stress from various environmental pollutants. Melanocytes reside in the basal layer of the interfollicular epidermis and are compensated by melanocyte stem cells in the follicular bulge area. Various stimuli such as eczema, microbial infection, ultraviolet light exposure, mechanical injury, and aging provoke skin inflammation. These acute or chronic inflammatory responses cause inflammatory cytokine production from epidermal keratinocytes as well as dermal fibroblasts and other cells, which in turn stimulate melanocytes, often resulting in skin pigmentation. It is confirmed by some recent studies that several interleukins (ILs) and other inflammatory mediators modulate the proliferation and differentiation of human epidermal melanocytes and also promote or inhibit expression of melanogenesis-related gene expression directly or indirectly, thereby participating in regulation of skin pigmentation. Understanding of mechanisms of skin pigmentation due to inflammation helps to elucidate the relationship between inflammation and skin pigmentation regulation and can guide development of new therapeutic pathways for treating pigmented dermatosis. This review covers the mechanistic aspects of skin pigmentation caused by inflammation.
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Envejecimiento/genética , Inflamación/genética , Melaninas/genética , Pigmentación de la Piel/genética , Envejecimiento/efectos de la radiación , Diferenciación Celular/efectos de la radiación , Humanos , Inflamación/patología , Queratinocitos/efectos de la radiación , Melanocitos/metabolismo , Melanocitos/efectos de la radiación , Piel/patología , Piel/efectos de la radiación , Pigmentación de la Piel/efectos de la radiación , Rayos Ultravioleta/efectos adversosRESUMEN
Nonmelanoma skin cancers occur primarily in individuals over the age of 60 and are characterized by an abundance of ultraviolet (UV) signature mutations in keratinocyte DNA. Though geriatric skin removes UV photoproducts from DNA less efficiently than young adult skin, it is not known whether the utilization of other prosurvival but potentially mutagenic DNA damage tolerance systems such as translesion synthesis (TLS) is altered in older individuals. Using monoubiquitination of the replicative DNA polymerase clamp protein PCNA (proliferating cell nuclear antigen) as a biochemical marker of TLS pathway activation, we find that UVB exposure of the skin of individuals over the age of 65 results in a higher level of PCNA monoubiquitination than in the skin of young adults. Furthermore, based on previous reports showing a role for deficient insulin-like growth factor-1 (IGF-1) signaling in altered UVB DNA damage responses in geriatric human skin, we find that both pharmacological inhibition of the IGF-1 receptor (IGF-1R) and deprivation of IGF-1 potentiate UVB-induced PCNA monoubiquitination in both human skin ex vivo and keratinocytes in vitro. Interestingly, though the TLS DNA polymerase Pol eta can accurately replicate the major photoproducts induced in DNA by UV radiation, we find that it fails to accumulate on chromatin in the absence of IGF-1R signaling and that this phenotype is correlated with increased mutagenesis in keratinocytes in vitro. Thus, altered IGF-1/IGF-1R signaling in geriatric skin may predispose epidermal keratinocytes to carry out a more mutagenic form of DNA synthesis following UVB exposure.
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Envejecimiento/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Antígeno Nuclear de Célula en Proliferación/metabolismo , Piel/metabolismo , Piel/efectos de la radiación , Ubiquitinación/efectos de la radiación , Rayos Ultravioleta/efectos adversos , Anciano , Envejecimiento/efectos de la radiación , Daño del ADN , Reparación del ADN/efectos de la radiación , Femenino , Humanos , Masculino , Transducción de Señal/efectos de la radiación , Piel/citologíaRESUMEN
BACKGROUND: The long-term consequences of chemotherapy and radiotherapy result in a high prevalence and early onset of age-related chronic diseases in survivors. We aimed to examine whether childhood and adolescent cancer survivors (CS) demonstrate biomarkers of accelerated aging. METHODS: We evaluated 50 young adult CS at 11 [8-15] years after cancer diagnosis, and 30 healthy, age and sex-matched controls, who were unexposed to cancer therapy. Using a machine-learning approach, we assessed factors discriminating CS from controls and compared selected biomarkers and lymphocyte subpopulations with data from the Framingham Heart Study (FHS) cohort and the Genotype Tissue Expression (GTEx) project. RESULTS: Survivors compared with controls had higher levels of C-reactive protein and fibrinogen. The surface expression of CD38 on T cells was increased, and there was an increase in the percentage of memory T cells in survivors, compared with the unexposed group. The relationships between above cell subpopulations and age were consistent in CS, FHS, and GTEx cohorts, but not in controls. CONCLUSIONS: Young pediatric cancer survivors differ from age-related controls in terms of activation of the adaptive immune system and chronic, low-grade inflammation. These changes resemble aging phenotype observed in older population. Further research in biomarkers of aging in young, adult childhood cancer survivors is warranted, as it may facilitate screening and prevention of comorbidities in this population.
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Inmunidad Adaptativa , Envejecimiento , Supervivientes de Cáncer , Inflamación/inmunología , ADP-Ribosil Ciclasa 1/análisis , Adolescente , Factores de Edad , Envejecimiento/efectos de los fármacos , Envejecimiento/genética , Envejecimiento/efectos de la radiación , Biomarcadores , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Senescencia Celular , Niño , Enfermedad Crónica , Femenino , Fibrinógeno/análisis , Humanos , Inflamación/sangre , Aprendizaje Automático , Masculino , Glicoproteínas de Membrana/análisis , Linfocitos T/inmunología , Adulto JovenRESUMEN
BACKGROUND: The landmark National Aeronautics and Space Administration Twins Study represented an integrated effort to launch human space life science research into the modern age of molecular- and "omics"-based studies. As part of the first One-Year Mission aboard the International Space Station, identical twin astronauts Scott and Mark Kelly were the subjects of this "out of this world" research opportunity. Telomeres, the natural ends of chromosomes that shorten with cell division and a host of lifestyle factors and stresses, are key molecular determinants of aging and aging trajectories. METHODS: We proposed that telomere length dynamics (changes over time) represent a particularly relevant and integrative biomarker for astronauts, as they reflect the combined experiences and environmental exposures encountered during spaceflight. Telomere length (quantitative polymerase chain reaction and telomere fluorescence in situ hybridization) and telomerase activity (quantitative polymerase chain reaction -telomere repeat amplification protocol) were longitudinally assessed in the space- and earth-bound twins. Chromosome aberrations (directional genomic hybridization), signatures of radiation exposure, were also evaluated. RESULTS: The twins had relatively similar telomere lengths before spaceflight, and the earth-bound twins' telomeres remained relatively stable over the course of the study. Surprisingly, the space twins' telomeres were longer during spaceflight, and upon return to Earth shortened rapidly, resulting in many more short telomeres after spaceflight than before. Chromosomal signatures of space radiation exposure were also elevated during spaceflight, and increased inversion frequencies persisted after spaceflight, suggestive of ongoing genome instability. CONCLUSION: Although the definitive mechanisms underlying such dramatic spaceflight-associated shifts in telomere length remain unclear, improved maintenance of telomere length has important implications for aging science and improving healthspan for those on Earth, as well.
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Envejecimiento/genética , Vuelo Espacial , Acortamiento del Telómero/fisiología , Telómero/metabolismo , Gemelos Monocigóticos/genética , Envejecimiento/efectos de la radiación , Radiación Cósmica/efectos adversos , Inestabilidad Genómica/efectos de la radiación , Humanos , Estudios Longitudinales , Masculino , Telomerasa/metabolismo , Acortamiento del Telómero/efectos de la radiación , Factores de TiempoRESUMEN
Astronauts undertaking long-duration space missions may be vulnerable to unique stressors that can impact human aging. Nevertheless, few studies have examined the relationship of mission duration with DNA-methylation-based biomarkers of aging in astronauts. Using data from the six participants of the Mars-500 mission, a high-fidelity 520-day ground simulation experiment, we tested relationships of mission duration with five longitudinally measured blood DNA-methylation-based metrics: DNAmGrimAge, DNAmPhenoAge, DNA-methylation-based estimator of telomere length (DNAmTL), mitotic divisions (epigenetic mitotic clock [epiTOC2]), and pace of aging (PoA). We provide evidence that, relative to baseline, mission duration was associated with significant decreases in epigenetic aging. However, only decreases in DNAmPhenoAge remained significant 7 days post-mission. We also observed significant changes in estimated proportions of plasmablasts, CD4T, CD8 naive, and natural killer (NK) cells. Only decreases in NK cells remained significant post-mission. If confirmed more broadly, these findings contribute insights to improve the understanding of the biological aging implications for individuals experiencing long-duration space travel.
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Envejecimiento/genética , Vuelo Espacial , Ingravidez , Adulto , Envejecimiento/efectos de la radiación , Astronautas , Metilación de ADN , Epigénesis Genética/efectos de la radiación , Epigenómica/métodos , Humanos , Recuento de Leucocitos/métodos , Leucocitos/metabolismo , Estudios Longitudinales , Masculino , Factores de TiempoRESUMEN
The study of long-lived and regenerative animal models has revealed diverse protective responses to stressors such as aging and tissue injury. Spiny mice (Acomys) are a unique mammalian model of skin wound regeneration, but their response to other types of physiological skin damage has not been investigated. In this study, we examine how spiny mouse skin responds to acute UVB damage or chronological aging compared to non-regenerative C57Bl/6 mice (M. musculus). We find that, compared to M. musculus, the skin epidermis in A. cahirinus experiences a similar UVB-induced increase in basal cell proliferation but exhibits increased epidermal turnover. Notably, A. cahirinus uniquely form a suprabasal layer co-expressing Keratin 14 and Keratin 10 after UVB exposure concomitant with reduced epidermal inflammatory signaling and reduced markers of DNA damage. In the context of aging, old M. musculus animals exhibit typical hallmarks including epidermal thinning, increased inflammatory signaling and senescence. However, these age-related changes are absent in old A. cahirinus skin. Overall, we find that A. cahirinus have evolved novel responses to skin damage that reveals new aspects of its regenerative phenotype.
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Envejecimiento/efectos de la radiación , Ratones/fisiología , Piel/efectos de la radiación , Rayos Ultravioleta/efectos adversos , Animales , Proliferación Celular/efectos de la radiación , Senescencia Celular/efectos de la radiación , Células Epidérmicas/citología , Células Epidérmicas/efectos de la radiación , Epidermis/fisiología , Epidermis/efectos de la radiación , Femenino , Masculino , Ratones Endogámicos C57BL , Piel/citologíaRESUMEN
Ageing involves significant neurophysiological changes that are both systematic while at the same time exhibiting divergent trajectories across individuals. These changes underlie cognitive impairments in elderly while also affecting the response of aged brains to interventions like transcranial direct current stimulation (tDCS). While the cognitive benefits of tDCS are more variable in elderly, older adults also respond differently to stimulation protocols compared to young adults. The age-related neurophysiological changes influencing the responsiveness to tDCS remain to be addressed in-depth. We review and discuss the premise that, in comparison to the better calibrated brain networks present in young adults, aged systems perform further away from a homoeostatic set-point. We argue that this age-related neurophysiological deviation from the homoeostatic optimum extends the leeway for tDCS to modulate the aged brain. This promotes the potency of immediate tDCS effects to induce directional plastic changes towards the homoeostatic equilibrium despite the impaired plasticity induction in elderly. We also consider how age-related neurophysiological changes pose specific challenges for tDCS that necessitate proper adaptations of stimulation protocols. Appreciating the distinctive properties of aged brains and the accompanying adjustment of stimulation parameters can increase the potency and reliability of tDCS as a treatment avenue in older adults.
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Envejecimiento/fisiología , Envejecimiento/efectos de la radiación , Encéfalo/fisiología , Encéfalo/efectos de la radiación , Anciano , Disfunción Cognitiva/terapia , Humanos , Reproducibilidad de los Resultados , Estimulación Transcraneal de Corriente Directa , Adulto JovenRESUMEN
Leaf senescence is a developmental process by which a plant actively remobilizes nutrients from aged and photosynthetically inefficient leaves to young growing ones by disassembling organelles and degrading macromolecules. Senescence is accelerated by age and environmental stresses such as prolonged darkness. Phytochrome B (phyB) inhibits leaf senescence by inhibiting phytochrome-interacting factor 4 (PIF4) and PIF5 in prolonged darkness. However, it remains unknown whether phyB mediates the temperature signal that regulates leaf senescence. We found the light-activated form of phyB (Pfr) remains active at least four days after a transfer to darkness at 20°C but is inactivated more rapidly at 28°C. This faster inactivation of Pfr further increases PIF4 protein levels at the higher ambient temperature. In addition, PIF4 mRNA levels rise faster after the transfer to darkness at high ambient temperature via a mechanism that depends on ELF3 but not phyB. Increased PIF4 protein then binds to the ORE1 promoter and activates its expression together with ABA and ethylene signaling, accelerating leaf senescence at high ambient temperature. Our results support a role for the phy-PIF signaling module in integrating not only light signaling but also temperature signaling in the regulation of leaf senescence.
Asunto(s)
Envejecimiento/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Fitocromo B/metabolismo , Hojas de la Planta/metabolismo , Ácido Abscísico/metabolismo , Envejecimiento/genética , Envejecimiento/efectos de la radiación , Arabidopsis/genética , Arabidopsis/efectos de la radiación , Proteínas de Arabidopsis/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Inmunoprecipitación de Cromatina , Oscuridad , Etilenos/metabolismo , Regulación de la Expresión Génica de las Plantas/genética , Regulación de la Expresión Génica de las Plantas/fisiología , Regulación de la Expresión Génica de las Plantas/efectos de la radiación , Luz , Reguladores del Crecimiento de las Plantas/farmacología , Hojas de la Planta/genética , Hojas de la Planta/fisiología , Hojas de la Planta/efectos de la radiación , Plantas Modificadas Genéticamente/genética , Transducción de Señal/genética , Transducción de Señal/fisiología , Transducción de Señal/efectos de la radiación , Temperatura , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
The age spectrum of human populations is shifting toward the older with larger proportions suffering physical decline. Mitochondria influence the pace of aging as the energy they provide for cellular function in the form of adenosine triphosphate (ATP) declines with age. Mitochondrial density is greatest in photoreceptors, particularly cones that have high energy demands and mediate color vision. Hence, the retina ages faster than other organs, with a 70% ATP reduction over life and a significant decline in photoreceptor function. Mitochondria have specific light absorbance characteristics influencing their performance. Longer wavelengths spanning 650->1,000 nm improve mitochondrial complex activity, membrane potential, and ATP production. Here, we use 670-nm light to improve photoreceptor performance and measure this psychophysically in those aged 28-72 years. Rod and cone performance declined significantly after approximately 40 years of age. 670-nm light had no impact in younger individuals, but in those around 40 years and older, significant improvements were obtained in color contrast sensitivity for the blue visual axis (tritan) known to display mitochondrial vulnerability. The red visual axis (protan) improved but not significantly. Rod thresholds also improved significantly in those >40 years. Using specific wavelengths to enhance mitochondrial performance will be significant in moderating the aging process in this metabolically demanding tissue.
Asunto(s)
Envejecimiento/fisiología , Mitocondrias/fisiología , Trastornos de la Visión/etiología , Adulto , Anciano , Envejecimiento/efectos de la radiación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mitocondrias/efectos de la radiación , Células Fotorreceptoras de Vertebrados/fisiología , Células Fotorreceptoras de Vertebrados/efectos de la radiaciónRESUMEN
Purpose: The bioluminescence reporter PER2::Luciferase (PER2::Luc) provides a powerful tool to study the regulation of biological clocks in explant tissues, including the retinal clock. However, the establishment of a standardized procedure to replicate experimental conditions and to enable meaningful comparisons between findings from different studies is still lacking. In addition, different parameters may affect the retinal circadian bioluminescence signal and its dynamic in in vitro assays. In the present study, we first evaluated the effect of sex and age on the main parameters of the mouse retinal clock. We then examined the impact of medium change on PER2::Luc rhythm and compared two light stimulation protocols of the retinal clock. Methods: In a first set of experiments, retinal explants from both male and female Per2Luc mice of different ages (1 to 8 months) are cultured and the period, phase, amplitude, and rhythmic power of PER2::Luc oscillations are analyzed. In a second set of experiments, we quantified the effect of a medium change done after 4, 6, 8, 9, or 10 days of culture on the phase and period of retinal explants. Finally, we compared the phase shift and the period change resulting from two methods of light stimulations of retinal explants: the first involved the transfer of the cultured tissues from the Lumicycle into a light stimulation chamber, while the second used a light delivery apparatus embedded in the Lumicycle. Results: We do not observe any sex-dependent effects on the amplitude, period, phase, and rhythmic power of the in vitro retinal PER2::Luc oscillations in animals aged of 2 to 3 months. The most remarkable effect of age is on the amplitude of PER2::Luc oscillations that significantly decrease from 1 to 4-5 months, whereas the endogenous period and rhythmic power increase slightly until 2 to 3 months and then do not change until 8 months. The phase is not affected by age. We then show that a medium change occurring after 4 days of culture does not alter the phase of PER2::Luc rhythm by comparison with day 0, whereas a medium change done after 6, 8, 9, or 10 days in culture advances the phase and lengthens the period. Finally, we observe that the physical displacement of the culture dishes containing retinal explants, even in complete darkness, induces a strong phase shift of PER2::Luc oscillations. Conclusions: Our work shows that the retina cultures are particularly sensitive to some aspects of the culture procedure, and it provides an accurate standard protocol to avoid biases due to artifactually induced phase shifts resulting from the medium change or physical displacement.
Asunto(s)
Técnicas de Cultivo de Célula/métodos , Relojes Circadianos , Genes Reporteros/genética , Mediciones Luminiscentes/métodos , Proteínas Circadianas Period/metabolismo , Retina/metabolismo , Envejecimiento/fisiología , Envejecimiento/efectos de la radiación , Animales , Relojes Biológicos/fisiología , Relojes Biológicos/efectos de la radiación , Células Cultivadas , Relojes Circadianos/efectos de la radiación , Ritmo Circadiano/fisiología , Ritmo Circadiano/efectos de la radiación , Femenino , Luz , Luciferasas/metabolismo , Mediciones Luminiscentes/instrumentación , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteínas Circadianas Period/genética , Retina/efectos de la radiaciónRESUMEN
The global population of individuals over the age of 65 is growing at an unprecedented rate and is expected to reach 1.6 billion by 2050. Most older individuals are affected by multiple chronic diseases, leading to complex drug treatments and increased risk of physical and cognitive disability. Improving or preserving the health and quality of life of these individuals is challenging due to a lack of well-established clinical guidelines. Physicians are often forced to engage in cycles of "trial and error" that are centered on palliative treatment of symptoms rather than the root cause, often resulting in dubious outcomes. Recently, geroscience challenged this view, proposing that the underlying biological mechanisms of aging are central to the global increase in susceptibility to disease and disability that occurs with aging. In fact, strong correlations have recently been revealed between health dimensions and phenotypes that are typical of aging, especially with autophagy, mitochondrial function, cellular senescence, and DNA methylation. Current research focuses on measuring the pace of aging to identify individuals who are "aging faster" to test and develop interventions that could prevent or delay the progression of multimorbidity and disability with aging. Understanding how the underlying biological mechanisms of aging connect to and impact longitudinal changes in health trajectories offers a unique opportunity to identify resilience mechanisms, their dynamic changes, and their impact on stress responses. Harnessing how to evoke and control resilience mechanisms in individuals with successful aging could lead to writing a new chapter in human medicine.
Asunto(s)
Envejecimiento/fisiología , Inestabilidad Genómica/genética , Inflamación/metabolismo , Mitocondrias/metabolismo , Células Madre/metabolismo , Homeostasis del Telómero/genética , Envejecimiento/genética , Envejecimiento/metabolismo , Envejecimiento/efectos de la radiación , Animales , Senescencia Celular/genética , Senescencia Celular/fisiología , Epigénesis Genética/efectos de los fármacos , Epigénesis Genética/genética , Inestabilidad Genómica/efectos de los fármacos , Inestabilidad Genómica/efectos de la radiación , Geriatría/métodos , Humanos , Morbilidad , Proteostasis/genética , Proteostasis/fisiología , Especies Reactivas de Oxígeno/metabolismo , Células Madre/fisiología , Homeostasis del Telómero/fisiologíaRESUMEN
Chlorophyll degradation is one of the most visible signs of leaf senescence. During senescence, chlorophyll is degraded in the multistep pheophorbide a oxygenase (PAO)/phyllobilin pathway. This pathway is tightly regulated at the transcriptional level, allowing coordinated and efficient remobilization of nitrogen toward sink organs. Using a combination of transcriptome and metabolite analyses during dark-induced senescence of Arabidopsis (Arabidopsis thaliana) mutants deficient in key steps of the PAO/phyllobilin pathway, we show an unanticipated role for one of the pathway intermediates, i.e. pheophorbide a Both jasmonic acid-related gene expression and jasmonic acid precursors specifically accumulated in pao1, a mutant deficient in PAO. We propose that pheophorbide a, the last intact porphyrin intermediate of chlorophyll degradation and a unique pathway "bottleneck," has been recruited as a signaling molecule of chloroplast metabolic status. Our work challenges the assumption that chlorophyll breakdown is merely a result of senescence, and proposes that the flux of pheophorbide a through the pathway acts in a feed-forward loop that remodels the nuclear transcriptome and controls the pace of chlorophyll degradation in senescing leaves.