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1.
Aging (Albany NY) ; 16(7): 5829-5855, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38613792

RESUMEN

Aging is characterized by declining health that results in decreased cellular resilience and neuromuscular function. The relationship between lifespan and health, and the influence of genetic background on that relationship, has important implications in the development of pharmacological anti-aging interventions. Here we assessed swimming performance as well as survival under thermal and oxidative stress across a nematode genetic diversity test panel to evaluate health effects for three compounds previously studied in the Caenorhabditis Intervention Testing Program and thought to promote longevity in different ways - NP1 (nitrophenyl piperazine-containing compound 1), propyl gallate, and resveratrol. Overall, we find the relationships among median lifespan, oxidative stress resistance, thermotolerance, and mobility vigor to be complex. We show that oxidative stress resistance and thermotolerance vary with compound intervention, genetic background, and age. The effects of tested compounds on swimming locomotion, in contrast, are largely species-specific. In this study, thermotolerance, but not oxidative stress or swimming ability, correlates with lifespan. Notably, some compounds exert strong impact on some health measures without an equally strong impact on lifespan. Our results demonstrate the importance of assessing health and lifespan across genetic backgrounds in the effort to identify reproducible anti-aging interventions, with data underscoring how personalized treatments might be required to optimize health benefits.


Asunto(s)
Caenorhabditis elegans , Longevidad , Estrés Oxidativo , Animales , Longevidad/efectos de los fármacos , Longevidad/genética , Estrés Oxidativo/efectos de los fármacos , Caenorhabditis elegans/efectos de los fármacos , Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiología , Resveratrol/farmacología , Envejecimiento/efectos de los fármacos , Envejecimiento/genética , Antecedentes Genéticos , Natación , Piperazinas/farmacología , Estilbenos/farmacología
2.
Proc Natl Acad Sci U S A ; 121(18): e2311028121, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38657052

RESUMEN

Increased cellular senescence burden contributes in part to age-related organ dysfunction and pathologies. In our study, using mouse models of natural aging, we observed structural and functional decline in the aged retina, which was accompanied by the accumulation of senescent cells and senescence-associated secretory phenotype factors. We further validated the senolytic and senomorphic properties of procyanidin C1 (PCC1) both in vitro and in vivo, the long-term treatment of which ameliorated age-related retinal impairment. Through high-throughput single-cell RNA sequencing (scRNA-seq), we comprehensively characterized the retinal landscape after PCC1 administration and deciphered the molecular basis underlying the senescence burden increment and elimination. By exploring the scRNA-seq database of age-related retinal disorders, we revealed the role of cellular senescence and the therapeutic potential of PCC1 in these pathologies. Overall, these results indicate the therapeutic effects of PCC1 on the aged retina and its potential use for treating age-related retinal disorders.


Asunto(s)
Envejecimiento , Catequina , Senescencia Celular , Proantocianidinas , Retina , Animales , Retina/metabolismo , Retina/efectos de los fármacos , Ratones , Proantocianidinas/farmacología , Proantocianidinas/metabolismo , Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismo , Senescencia Celular/efectos de los fármacos , Catequina/farmacología , Catequina/metabolismo , Catequina/química , Biflavonoides/farmacología , Senoterapéuticos/farmacología , Ratones Endogámicos C57BL , Humanos , Enfermedades de la Retina/tratamiento farmacológico , Enfermedades de la Retina/metabolismo , Enfermedades de la Retina/patología
4.
Artículo en Inglés | MEDLINE | ID: mdl-37855709

RESUMEN

This study investigates the effects of peroxisome proliferator-activated receptor gamma (PPARγ) inhibition on bone and immune cell profiles in aged female mice, as well as in vitro stromal stem cell osteogenic differentiation and inflammation gene expression. The hypothesis was that inhibition of PPARγ would increase bone mass and alter immune and other cellular functions. Our results showed that treatment with PPARγ antagonist GW9662 for 6 weeks reduced bone volume and trabecular number and increased trabecular spacing. However, inhibition of PPARγ had no significant effect on marrow and spleen immune cell composition in aged female mice. In vitro experiments indicated that GW9662 treatment increased the expression of osteogenic genes but did not affect adipogenic genes. Additionally, GW9662 treatment decreased the expression of several inflammation-related genes. Overall, these findings suggest that PPARγ inhibition may have adverse effects on bone in aged female mice.


Asunto(s)
Anilidas , Osteogénesis , PPAR gamma , Animales , Femenino , Ratones , Adipogénesis , Anilidas/administración & dosificación , Inflamación , Osteogénesis/efectos de los fármacos , PPAR gamma/antagonistas & inhibidores , Huesos/efectos de los fármacos , Envejecimiento/efectos de los fármacos , Envejecimiento/patología
5.
Nature ; 620(7976): 1071-1079, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37587343

RESUMEN

Identifying therapeutics to delay, and potentially reverse, age-related cognitive decline is critical in light of the increased incidence of dementia-related disorders forecasted in the growing older population1. Here we show that platelet factors transfer the benefits of young blood to the ageing brain. Systemic exposure of aged male mice to a fraction of blood plasma from young mice containing platelets decreased neuroinflammation in the hippocampus at the transcriptional and cellular level and ameliorated hippocampal-dependent cognitive impairments. Circulating levels of the platelet-derived chemokine platelet factor 4 (PF4) (also known as CXCL4) were elevated in blood plasma preparations of young mice and humans relative to older individuals. Systemic administration of exogenous PF4 attenuated age-related hippocampal neuroinflammation, elicited synaptic-plasticity-related molecular changes and improved cognition in aged mice. We implicate decreased levels of circulating pro-ageing immune factors and restoration of the ageing peripheral immune system in the beneficial effects of systemic PF4 on the aged brain. Mechanistically, we identified CXCR3 as a chemokine receptor that, in part, mediates the cellular, molecular and cognitive benefits of systemic PF4 on the aged brain. Together, our data identify platelet-derived factors as potential therapeutic targets to abate inflammation and rescue cognition in old age.


Asunto(s)
Envejecimiento , Cognición , Disfunción Cognitiva , Enfermedades Neuroinflamatorias , Nootrópicos , Factor Plaquetario 4 , Animales , Masculino , Ratones , Envejecimiento/sangre , Envejecimiento/efectos de los fármacos , Envejecimiento/fisiología , Cognición/efectos de los fármacos , Cognición/fisiología , Enfermedades Neuroinflamatorias/sangre , Enfermedades Neuroinflamatorias/complicaciones , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/prevención & control , Factor Plaquetario 4/sangre , Factor Plaquetario 4/metabolismo , Factor Plaquetario 4/farmacología , Factor Plaquetario 4/uso terapéutico , Nootrópicos/sangre , Nootrópicos/metabolismo , Nootrópicos/farmacología , Nootrópicos/uso terapéutico , Plasma/química , Hipocampo/efectos de los fármacos , Hipocampo/fisiología , Disfunción Cognitiva/sangre , Disfunción Cognitiva/complicaciones , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/prevención & control , Transcripción Genética/efectos de los fármacos , Plasticidad Neuronal/efectos de los fármacos
7.
Science ; 380(6649): eabn9257, 2023 06 09.
Artículo en Inglés | MEDLINE | ID: mdl-37289866

RESUMEN

Aging is associated with changes in circulating levels of various molecules, some of which remain undefined. We find that concentrations of circulating taurine decline with aging in mice, monkeys, and humans. A reversal of this decline through taurine supplementation increased the health span (the period of healthy living) and life span in mice and health span in monkeys. Mechanistically, taurine reduced cellular senescence, protected against telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA damage, and attenuated inflammaging. In humans, lower taurine concentrations correlated with several age-related diseases and taurine concentrations increased after acute endurance exercise. Thus, taurine deficiency may be a driver of aging because its reversal increases health span in worms, rodents, and primates and life span in worms and rodents. Clinical trials in humans seem warranted to test whether taurine deficiency might drive aging in humans.


Asunto(s)
Envejecimiento , Taurina , Animales , Humanos , Ratones , Envejecimiento/sangre , Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismo , Senescencia Celular , Haplorrinos , Longevidad/efectos de los fármacos , Longevidad/fisiología , Taurina/sangre , Taurina/deficiencia , Taurina/farmacología , Suplementos Dietéticos , Daño del ADN/efectos de los fármacos , Telomerasa/metabolismo
8.
Phytochemistry ; 213: 113751, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37307887

RESUMEN

Boswellia dalzielii is a resin-producing tree endemic to West and Central Africa, used by local populations for various medicinal purposes. In this study, B. dalzielii gum resin was analyzed by GC-MS and UHPLC-MS to identify and quantify volatile and non-volatile compounds. Its main volatile constituents were α-pinene (54.9%), followed by α-thujene (4.4%) and α-phellandren-8-ol (4.0%). Pentacyclic triterpenoids such as ß-boswellic acids and their derivatives were quantified by UHPLC-MS and their content was shown to reach around 22% of the gum resin. Since some of the volatile and non-volatile compounds identified in this work are known to possess biological effects, the bioactivities of B. dalzielii ethanolic extract, essential oil, as well as fractions of the oil and extract were evaluated. Some of these samples exhibited interesting anti-inflammatory properties, and their antioxidant, anti-ageing and skin-bleaching activities were also tested.


Asunto(s)
Boswellia , Fitoquímicos , Resinas de Plantas , Envejecimiento/efectos de los fármacos , Antiinflamatorios/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Boswellia/química , Aceites Volátiles/farmacología , Aceites Volátiles/química , Fitoquímicos/química , Fitoquímicos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Resinas de Plantas/química , Preparaciones para Aclaramiento de la Piel/química , Preparaciones para Aclaramiento de la Piel/farmacología , Triterpenos/química , Triterpenos/farmacología
9.
Rejuvenation Res ; 26(4): 139-146, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37166369

RESUMEN

Acarbose (ACA), a well-studied and effective inhibitor of α-amylase and α-glucosidase, is a postprandial-acting antidiabetic medicine. The membrane of the erythrocyte is an excellent tool for analyzing different physiological and biochemical activities since it experiences a range of metabolic alterations throughout aging. It is uncertain if ACA modulates erythrocyte membrane activities in an age-dependent manner. As a result, the current study was conducted to explore the influence of ACA on age-dependent deteriorated functions of transporters/exchangers, disrupted levels of various biomarkers such as lipid hydroperoxides (LHs), protein carbonyl (PCO), sialic acid (SA), total thiol (-SH), and erythrocyte membrane osmotic fragility. In addition to a concurrent increase in Na+/H+ exchanger activity and concentration of LH, PCO, and osmotic fragility, we also detected a considerable decrease in membrane-linked activities of Ca2+-ATPase (PMCA) and Na+/K+-ATPase (NKA), as well as concentrations of SA and -SH in old-aged rats. The aging-induced impairment of the activities of membrane-bound ATPases and the changed levels of redox biomarkers were shown to be effectively restored by ACA treatment.


Asunto(s)
Acarbosa , Envejecimiento , Membrana Eritrocítica , Inhibidores de Glicósido Hidrolasas , ATPasas Transportadoras de Calcio de la Membrana Plasmática , ATPasa Intercambiadora de Sodio-Potasio , Acarbosa/farmacología , Inhibidores de Glicósido Hidrolasas/farmacología , Membrana Eritrocítica/química , Membrana Eritrocítica/efectos de los fármacos , Membrana Eritrocítica/enzimología , Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismo , Peróxidos Lipídicos/análisis , Ácidos Siálicos/análisis , Carbonilación Proteica/efectos de los fármacos , Compuestos de Sulfhidrilo/análisis , Fragilidad Osmótica/efectos de los fármacos , Animales , Ratas , Masculino , Ratas Wistar , ATPasas Transportadoras de Calcio de la Membrana Plasmática/análisis , ATPasas Transportadoras de Calcio de la Membrana Plasmática/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/análisis , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Oxidación-Reducción/efectos de los fármacos , Biomarcadores/análisis , Biomarcadores/metabolismo
10.
Nat Commun ; 14(1): 2779, 2023 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-37188705

RESUMEN

Reversible and sub-lethal stresses to the mitochondria elicit a program of compensatory responses that ultimately improve mitochondrial function, a conserved anti-aging mechanism termed mitohormesis. Here, we show that harmol, a member of the beta-carbolines family with anti-depressant properties, improves mitochondrial function and metabolic parameters, and extends healthspan. Treatment with harmol induces a transient mitochondrial depolarization, a strong mitophagy response, and the AMPK compensatory pathway both in cultured C2C12 myotubes and in male mouse liver, brown adipose tissue and muscle, even though harmol crosses poorly the blood-brain barrier. Mechanistically, simultaneous modulation of the targets of harmol monoamine-oxidase B and GABA-A receptor reproduces harmol-induced mitochondrial improvements. Diet-induced pre-diabetic male mice improve their glucose tolerance, liver steatosis and insulin sensitivity after treatment with harmol. Harmol or a combination of monoamine oxidase B and GABA-A receptor modulators extend the lifespan of hermaphrodite Caenorhabditis elegans or female Drosophila melanogaster. Finally, two-year-old male and female mice treated with harmol exhibit delayed frailty onset with improved glycemia, exercise performance and strength. Our results reveal that peripheral targeting of monoamine oxidase B and GABA-A receptor, common antidepressant targets, extends healthspan through mitohormesis.


Asunto(s)
Envejecimiento , Antidepresivos , Harmina , Mitocondrias , Mitofagia , Monoaminooxidasa , Receptores de GABA-A , Harmina/análogos & derivados , Harmina/farmacología , Antidepresivos/farmacología , Mitocondrias/efectos de los fármacos , Mitofagia/efectos de los fármacos , Fibras Musculares Esqueléticas/efectos de los fármacos , Quinasas de la Proteína-Quinasa Activada por el AMP/metabolismo , Músculo Esquelético/efectos de los fármacos , Hígado/efectos de los fármacos , Envejecimiento/efectos de los fármacos , Resistencia a la Insulina , Intolerancia a la Glucosa/metabolismo , Estado Prediabético/metabolismo , Monoaminooxidasa/metabolismo , Receptores de GABA-A/metabolismo , Longevidad/efectos de los fármacos , Caenorhabditis elegans , Drosophila melanogaster , Fragilidad/prevención & control , Condicionamiento Físico Animal , Modelos Animales , Masculino , Femenino , Animales , Ratones , Hígado Graso/metabolismo , Tejido Adiposo Pardo/efectos de los fármacos
11.
Zebrafish ; 20(2): 55-66, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37071853

RESUMEN

Population aging is a global problem worldwide, and the discovery of antiaging drugs and knowledge of their potential molecular mechanisms are research hotspots in biomedical field. Tetrahydroxystilbene glucoside (TSG) is a natural component isolated from Heshouwu (Polygonum multiflorum Thunb.). It has been widely used to treat various chronic diseases for its remarkable biological activities. In this study, we successfully established aging larval zebrafish by exposing larvae to 2 mM hydrogen peroxide (H2O2). Using this aging model, we assessed the antiaging effect of TSG with different concentrations (25-100 µg/mL). After being treated with H2O2, zebrafish showed the obvious aging-associated phenotypes characterized by higher senescence-associated ß-galactosidase activity, significantly downregulated expression of sirtuin 1 (sirt1) and telomerase reverse transcriptase (tert), and upregulated serpine1 mRNA level compared to the control group. TSG pretreatment delayed the aging process of oxidative stress-induced zebrafish, indicative of the reduced positive rate of senescence-associated ß-galactosidase, improved swimming velocity, and stimulus-response capacity. Further studies proved that TSG could suppress reactive oxygen species production and enhance the activity of antioxidant enzymes superoxide dismutase and catalase. TSG also inhibited the H2O2-induced expressions of inflammation-related genes il-1ß, il-6, cxcl-c1c, and il-8 in aging zebrafish, but it did not affect apoptosis-related genes (bcl-2, bax, and caspase-3) of aging zebrafish. In conclusion, TSG can protect against aging by regulating the antioxidative genes and enzyme activity, as well as inflammation in larval zebrafish, providing insight into the application of TSG for clinical treatment of aging or aging-related diseases.


Asunto(s)
Envejecimiento , Estilbenos , Pez Cebra , Animales , Envejecimiento/efectos de los fármacos , Antioxidantes/farmacología , Peróxido de Hidrógeno/toxicidad , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Estilbenos/farmacología , Pez Cebra/crecimiento & desarrollo , Larva/efectos de los fármacos , Larva/crecimiento & desarrollo , Inflamación
12.
J Cell Mol Med ; 27(10): 1398-1409, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37032511

RESUMEN

Senescence of vascular endothelial cells is the major risk of vascular dysfunction and disease among elderly people. Parishin, which is a phenolic glucoside derived from Gastrodia elata, significantly prolonged yeast lifespan. However, the action of parishin in vascular ageing remains poorly understood. Here, we treated human coronary artery endothelial cells (HCAEC) and naturally aged mice by parishin. Parishin alleviated HCAEC senescence and general age-related features in vascular tissue in naturally aged mice. Network pharmacology approach was applied to determine the compound-target networks of parishin. Our analysis indicated that parishin had a strong binding affinity for Klotho. Expression of Klotho, a protein of age-related declines, was upregulated by parishin in serum and vascular tissue in naturally aged mice. Furthermore, FoxO1, on Klotho/FoxO1 signalling pathway, was increased in the parishin-intervened group, accompanied by the downregulated phosphorylated FoxO1. Taken together, parishin can increase Klotho expression to alleviate vascular endothelial cell senescence and vascular ageing.


Asunto(s)
Envejecimiento , Glucósidos , Proteínas Klotho , Animales , Ratones , Envejecimiento/sangre , Envejecimiento/efectos de los fármacos , Envejecimiento/genética , Células Endoteliales , Proteínas Klotho/sangre , Proteínas Klotho/metabolismo , Activación Transcripcional/efectos de los fármacos , Regulación hacia Arriba , Humanos , Glucósidos/farmacología
13.
J Gerontol A Biol Sci Med Sci ; 78(4): 596-602, 2023 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-36630695

RESUMEN

Aging is a complex process in which the structure and function of various tissues and organs gradually decline with age, and ovarian aging affects the reproductive capacity of females and induces age-related diseases. Resveratrol, a natural polyphenol compound, extends the life span and has a protective effect on the ovaries of vertebrates. However, the effects and underlying mechanisms of resveratrol delaying ovarian aging are unclear. In this study, using an annual fish Nothobranchius guentheri, we demonstrated that senescence-associated-beta-galactosidase (SA-ß-gal) activity and lipofuscin accumulation increased with age in the ovaries, and resveratrol reversed this phenomenon. Resveratrol increased proliferating cell nuclear antigen (PCNA) expression and the oocyte proportions of the primary growth stage, cortical alveolus stage and vitellogenesis stage, and decreased the number of atretic follicles in the ovaries of 6-, 9-, and 12-month-old fish. Moreover, the expression of SIRT1 and NRF2 decreased and the levels of NF-κB, pro-inflammatory cytokines IL-1ß, TNF-α, and IL-8 and endoplasmic reticulum (ER) stress markers GRP78 and CHOP increased with aging, while resveratrol up-regulated SIRT1 and NRF2 expression and down-regulated NF-κB, IL-1ß, TNF-α, IL-8, GRP78, and CHOP levels in the ovaries of 6- and 9-month-old fish. In HEK293T cells, knockdown SIRT1 decreased NRF2 and increased NF-κB p65, pro-inflammatory cytokines (IL-1ß and TNF-α), and ER stress marker GRP78 expression markedly. Silencing SIRT1 and then treating the cells with resveratrol significantly reversed the phenomenon. Collectively, resveratrol might activate SIRT1/NRF2 to reduce inflammation and ER stress, and finally delay ovarian aging in a short-lived fish. This study highlights the protective effect and mechanism of resveratrol on ovarian aging.


Asunto(s)
Envejecimiento , Estrés del Retículo Endoplásmico , Inflamación , Ovario , Resveratrol , Animales , Femenino , Humanos , Envejecimiento/efectos de los fármacos , Citocinas/metabolismo , Chaperón BiP del Retículo Endoplásmico , Células HEK293 , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Interleucina-8 , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Ovario/metabolismo , Resveratrol/farmacología , Sirtuina 1/metabolismo , Factor de Necrosis Tumoral alfa , Estrés del Retículo Endoplásmico/efectos de los fármacos
14.
São Paulo; s.n; 2023. 33 p.
Tesis en Portugués | Coleciona SUS, Sec. Munic. Saúde SP, HSPM-Producao, Sec. Munic. Saúde SP | ID: biblio-1532794

RESUMEN

A dermatoporose é a síndrome de fragilidade cutânea. Acomete principalmente indivíduos acima de 60 anos, com maior prevalência no sexo feminino. Os principais fatores de risco são: envelhecimento, exposição solar intensa e uso de corticoterapia tópica e sistêmica. Se manifesta clinicamente por atrofia cutânea, púrpuras senis, pseudo cicatrizes estrelares e lacerações, podendo evoluir com hematomas dissecantes e infecções graves. Trata-se de uma doença com grande impacto na qualidade de vida dos pacientes e, até o presente momento, não há terapias com resultados satisfatórios. Hidratação, vitamina C tópica e oral, luz intensa pulsada foram algumas das terapêuticas estudadas. A hidroxiapatita de cálcio é um bioestimulador de colágeno composto por microesferas em um veículo de carboximetilcelulose (Radiesse®). Tem sido usada para estimular a produção endógena de colágeno e consequentemente melhorar a qualidade e espessura da pele. Este efeito do produto poderia melhorar o quadro clínico da dermatoporose. O estudo teve como objetivo avaliar a melhora das lesões purpúricas e da atrofia da pele após aplicação de Radiesse® no antebraço de 5 pacientes portadores de dermatoporose no setor de Dermatologia do Hospital do Servidor Público Municipal de São Paulo. Os 5 pacientes foram submetidos a aplicação de Radiesse® nos antebraços e foram avaliadas 45 e 90 dias após o procedimento, o número de lesões purpúricas, grau de atrofia da pele através do teste de pinçamento e realizado comparação fotográfica. Após o tratamento, observou-se melhora do número das lesões purpúricas, melhora da atrofia da pele e melhora da qualidade de pele quando comparada fotograficamente. Dessa forma, o tratamento com Radiesse® mostrou-se promissor, com resultados satisfatórios e com um bom perfil de segurança. Palavras-chave: Dermatoporose. Púrpura senil. Radiesse. Bioestimulador. Tratamento.


Asunto(s)
Púrpura/tratamiento farmacológico , Atrofia/diagnóstico , Piel/efectos de los fármacos , Enfermedades de la Piel/diagnóstico , Envejecimiento/efectos de los fármacos , Carboximetilcelulosa de Sodio/administración & dosificación , Envejecimiento de la Piel/efectos de los fármacos , Corticoesteroides/efectos adversos , Deshidroepiandrosterona/fisiología , Durapatita/administración & dosificación , Durapatita/uso terapéutico , Terapia por Luz de Baja Intensidad
15.
Arq. ciências saúde UNIPAR ; 26(3): 1229-1247, set-dez. 2022.
Artículo en Portugués | LILACS | ID: biblio-1414495

RESUMEN

Mesmo em tempos modernos, os grandes avanços tecnológicos não permitem de forma comprovada retardar o envelhecimento nos seres humanos. Neste sentido, uma das estratégias é o uso moléculas químicas naturais que possuem a ação de ativadores de telomerase, uma vez de que a telomerase é uma ribonucleoproteína transcriptase reversa que possui a função de alongar os telômeros e neutralizar a erosão normal dos telômeros. Neste contexto, este estudo de revisão dedicou-se a aprofundar o conhecimento sobre o uso de moléculas químicas naturais derivadas de plantas que possuem função de ativadores de telomerase para atividade anti-aging. Inúmeras moléculas têm sido propostas e, estudas os seus mecanismos com o intuito de desenvolver novas ferramentas para prevenir/retardar e tratar doenças relacionadas a idade e o envelhecimento. Adicionalmente, o uso de moléculas como ativadores da telomerase têm sido um meio de prolongar o encurtamento dos temoleros, como no caso, de moléculas isolada da erva Astragalus membranaceus (TA-65), curcumina, silbinina e alicina; ademais, outras moléculas de origem natural possuem atividade anti-aging comprovadas, conforme reportadas nesta revisão. Sendo assim, a procura por biomarcadores à base de compostos químicos naturais que estimulem a telomerase, a fim de prolongar a vida dos telômero e assim, retardar o processo de envelhecimento do organismo têm despertado o interesse de diversos pesquisadores ao redor do mundo.


Even in modern times, the great technological advances do not allow in a proven way to delay aging in humans. In this sense, one of the strategies is the use of natural chemical molecules that have telomerase activators, since telomerase is a ribonucleoprotein reverse transcriptase that has the function of lengthening telomeres and neutralizing the normal erosion of telomeres. In this context, this review study was dedicated to deepening the knowledge about the use of natural chemical molecules derived from plants that have telomerase activator function for anti-aging activity. Numerous molecules have been proposed and their mechanisms studied in order to develop new tools to prevent/delay and treat aging-related diseases. Additionally, the use of molecules as telomerase activators has been a means of prolonging the shortening of temolers, as in the case of molecules isolated from the herb Astragalus membranaceus (TA-65), curcumin, silbinin and allicin; in addition, other molecules of natural origin have proven anti-aging activity, as reported in this review. Therefore, the search for biomarkers based on natural chemical compounds that stimulate telomerase in order to prolong the life of telomeres and, thus delay the aging process of the organism has aroused the interest of several researchers around the world.


Aún en los tiempos modernos, los grandes avances tecnológicos no permiten de manera comprobada retrasar el envejecimiento en los humanos. En este sentido, una de las estrategias es el uso de moléculas químicas naturales que tengan activadores de la telomerasa, ya que la telomerasa es una ribonucleoproteína transcriptasa inversa que tiene la función de alargar los telómeros y neutralizar la erosión normal de los telómeros. En este contexto, este estudio de revisión se dedicó a profundizar en el conocimiento sobre el uso de moléculas químicas naturales derivadas de plantas que tienen función activadora de la telomerasa para la actividad antienvejecimiento. Se han propuesto numerosas moléculas y se han estudiado sus mecanismos para desarrollar nuevas herramientas para prevenir/retrasar y tratar enfermedades relacionadas con el envejecimiento. Adicionalmente, el uso de moléculas como activadores de la telomerasa ha sido un medio para prolongar el acortamiento de temolers, como es el caso de moléculas aisladas de la hierba Astragalus membranaceus (TA-65), curcumina, silbinina y alicina; además, otras moléculas de origen natural han demostrado actividad antienvejecimiento, como se reporta en esta revisión. Por ello, la búsqueda de biomarcadores basados en compuestos químicos naturales que estimulen la telomerasa para prolongar la vida de los telómeros y así retrasar el proceso de envejecimiento del organismo ha despertado el interés de varios investigadores a nivel mundial.


Asunto(s)
Productos Biológicos , Envejecimiento/efectos de los fármacos , Telomerasa , ADN , Telómero , Astragalus propinquus , Curcuma/efectos de los fármacos
16.
Int J Mol Sci ; 23(14)2022 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-35886936

RESUMEN

Cholesterol metabolism seems dysregulated and linked to amyloid-ß (Aß) formation in neurodegeneration, but the underlying mechanisms are poorly known. Resveratrol (RSV) is a polyphenol with antioxidant activity and neuroprotective properties. Here, we analyzed the effect of age and RSV supplementation on cholesterol metabolism in the brain and blood serum, and its potential link to Aß processing, in SAMP8 mice-an animal model of aging and Alzheimer's disease. In the brain, our results revealed an age-related increase in ApoE and unesterified cholesterol in the plasma membrane whereas LDL receptor, HMG-CoA reductase, HMG-CoA-C1 synthase, and ABCA1 transporter remained unaltered. Furthermore, BACE-1 and APP gene expression was decreased. This dysregulation could be involved in the amyloidogenic processing pathway of APP towards Aß formation. In turn, RSV exhibited an age-dependent effect. While levels of unesterified cholesterol in the plasma membrane were not affected by RSV, several participants in cholesterol uptake, release, and de novo synthesis differed, depending on age. Thus, RSV supplementation exhibited a different neuroprotective effect acting on Aß processing or cholesterol metabolism in the brain at earlier or later ages, respectively. In blood serum, HDL lipoprotein and free cholesterol were increased by age, whereas VLDL and LDL lipoproteins remained unaltered. Again, the protective effect of RSV by decreasing the LDL or increasing the HDL levels also seems to depend on the intervention's moment. In conclusion, age is a prominent factor for cholesterol metabolism dysregulation in the brain of SAMP8 mice and influences the protective effects of RSV through cholesterol metabolism and Aß processing.


Asunto(s)
Envejecimiento , Enfermedad de Alzheimer , Péptidos beta-Amiloides , Colesterol , Fármacos Neuroprotectores , Resveratrol , Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismo , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Colesterol/metabolismo , Modelos Animales de Enfermedad , Ratones , Fármacos Neuroprotectores/farmacología , Resveratrol/farmacología
17.
Neurotoxicology ; 91: 60-68, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35537655

RESUMEN

Astragalin (AST) is a natural flavonoid with excellent antioxidant and anti-inflammatory activities. However, whether AST is an effective chemical for neuronal protection and its underlying mechanisms remain to be elucidated. In this study, we established a mouse model of cognitive impairment and aging-like phenotype induced by sequential administration of AlCl3 and D-galactose (Gal). We found that AST effectively ameliorated cognitive impairment in the model mice and improved their learning and memory performance in the Morris water maze (MWM) test. AlCl3/Gal-induced activation of astrocytes and microglia and inflammation were observed by immunohistochemistry and immunofluorescence, but could be attenuated by AST. In addition, alterations in oxidative stress-regulating enzymes or markers, including T-SOD, T-AOC, CAT, GSH-Px, and MDA, as well as the pro-inflammatory factors TNF-α, IL-1ß, and IL-6, were restored. At the mechanistic level, AlCl3/Gal-intoxicated mice showed a significant elevation of Notch/HES-1 and NF-κB signaling axis corresponding to microglia activation and inflammation. AST attenuated the activation of Notch/HES-1 and NF-κB signaling axis, thus reducing the inflammation. In summary, AST is a promising natural product to protect neurons from toxin-induced injury, indicating its therapeutic potential for neurological disorders.


Asunto(s)
Envejecimiento , Antiinflamatorios no Esteroideos , Quempferoles , Enfermedades Neuroinflamatorias , Fármacos Neuroprotectores , Estrés Oxidativo , Envejecimiento/efectos de los fármacos , Animales , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/uso terapéutico , Modelos Animales de Enfermedad , Galactosa/toxicidad , Quempferoles/farmacología , Quempferoles/uso terapéutico , Ratones , FN-kappa B/metabolismo , Enfermedades Neuroinflamatorias/inducido químicamente , Enfermedades Neuroinflamatorias/prevención & control , Fármacos Neuroprotectores/uso terapéutico , Estrés Oxidativo/efectos de los fármacos
18.
J Exp Zool A Ecol Integr Physiol ; 337(6): 600-611, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35286779

RESUMEN

d-galactose (DG)-induced rodent aging model has widely been used for the study of age-related dysfunctions of various organs, including gonads and uterus. Antidiabetic drug metformin has gained an attention as antiaging drug in model organism and human but its effect on uterus has not been studied in relation to induced aging. Therefore, we investigated the effect of metformin on uterus of DG-induced aging mice model. Mice were randomly divided into three groups, that is, control (CN), DG-induced aging model and aging model treated with metformin. Histomorphometric results showed significantly decreased number of uterine glands, endometrial thickness, and increased luminal epithelium height in aging model. Furthermore, metformin resumed the number of uterine glands, endometrial thickness, and luminal epithelium height up to CN group. Metformin has also significantly decreased the age-associated oxidative stress (malondialdehyde and lipid hydroperoxide). Superoxide dismutase was significantly decreased in both treated groups compared to the CN group. However, catalase and glutathione peroxidase enzymes were significantly increased by metformin compared to the aging model. Immunostaining of active caspase3 and BAX were intense in the endometrium of aging model compare to CN- and metformin-treated groups. Localization of B-cell lymphoma 2 (Bcl2) showed intense immunostaining in the uterus of CN- and metformin-treated groups, with mild immunostaining in aging model. Our observations suggested that metformin treatment might be helpful for management of age-associated uterine dysfunctions. Moreover, it may be concluded that metformin might ameliorate uterine dysfunctions by reducing oxidative stress, suppressing apoptosis, and increasing the survival/antiapoptotic protein Bcl2.


Asunto(s)
Envejecimiento , Metformina , Estrés Oxidativo , Útero , Envejecimiento/efectos de los fármacos , Animales , Caspasa 3 , Femenino , Galactosa , Metformina/farmacología , Ratones , Útero/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismo
19.
Geriatr Gerontol Int ; 22(5): 433-440, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35352454

RESUMEN

AIMS: Aging is a critical contributing factor for cardiovascular diseases. The d-galactose-induced accelerated aging model is comparable to physiological aging from the cellular to the physiological level. The d-galactose treatment induces mitochondrial dysfunction, increased reactive oxygen species (ROS) production, and upregulation of senescence-related genes. Cordycepin, a functional element in Chinese traditional medicine, has multiple beneficial effects as an antioxidant and ROS scavenger, and has been reported to be effective in a number of ischemia models. This paper aims to investigate the cardioprotective effects of cordycepin in the d-galactose accelerated aging model. METHODS: In the current study, we employed the d-galactose accelerated aging model to study the cardioprotective effect of cordycepin. Eight-week-old Sprague-Dawley rats, randomly divided into five groups, were given vehicle, d-galactose (150 mg/kg/day), and cordycepin at 5, 10, and 20 mg/kg per day. At the end of the 8-week treatment, rat cardiac structure and function were assessed with echocardiographic imaging and hemodynamic parameter analysis. RESULTS: Cordycepin upregulated the expression of Klotho in serum and heart tissues. The expressions of senescence markers ß-galactosidase, p21, and oxidative stress marker malondialdehyde (MDA) were downregulated by cordycepin treatment. Reduction of levels and activity of the antioxidant factors superoxide dismutase (SOD) and catalase (CAT) induced by by d-galactose treatment was ameliorated by cordycepin. Furthermore, cordycepin activated AMPK signaling in d-galactose-treated rats. After 8 weeks of treatment, we found that cordycepin improved myocardia contractility and hypertension caused by d-galactose treatment. Mechanistically, reduced expression of the Klotho protein SOD1 caused by d-galactose was recovered in rats co-treated with cordycepin. CONCLUSION: Cordycepin could protect against cardiac dysfunction in a d-galactose-induced aging rat model, suggesting the therapeutic cardioprotective potential of cordycepin in aging. Geriatr Gerontol Int 2022; 22: 433-440.


Asunto(s)
Envejecimiento , Antioxidantes , Desoxiadenosinas , Animales , Ratas , Envejecimiento/efectos de los fármacos , Antioxidantes/farmacología , Desoxiadenosinas/farmacología , Galactosa/toxicidad , Malondialdehído , Estrés Oxidativo , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno
20.
Sci Rep ; 12(1): 2425, 2022 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-35165353

RESUMEN

Senolytics are a class of drugs that selectively remove senescent cells. Dasatinib and quercetin have been discovered, and their combination has shown various anti-ageing effects. The SAMP10 mouse strain is a model of brain ageing. Here, we investigated the effect of combination on frailty characteristics in SAMP10. By comparing SAMP10 with SAMR1 mice as normal ageing controls, we investigated some frailty characteristics. Frailty was assessed at 18-38 weeks of age with a clinical frailty index. Motor and cognitive function of these mice were evaluated using behavioral experiments. SAMP10 mice were divided into vehicle and combination, and these functions and histological changes in the brain hippocampus were investigated. Finally, the in vitro effects of combination on oxidative stress-induced senescent muscle and neuronal cells were investigated. As a result, we found that frailty index was higher in SAMP10 than SAMR1. Motor and cognitive function were worse in SAMP10 than SAMR1. Furthermore, combination therapy improved frailty, motor and cognitive function, and the senescent phenotype of the hippocampus compared with vehicle in SAMP10. In summary, SAMP10 showed more marked frailty characteristics than SAMR1, and dasatinib and quercetin attenuated them in SAMP10. From our results, senolytic therapy might contribute protective effects against frailty.


Asunto(s)
Envejecimiento/efectos de los fármacos , Antioxidantes/administración & dosificación , Senescencia Celular/efectos de los fármacos , Dasatinib/administración & dosificación , Fragilidad/tratamiento farmacológico , Quercetina/administración & dosificación , Senoterapéuticos/administración & dosificación , Envejecimiento/metabolismo , Animales , Conducta Animal/efectos de los fármacos , Línea Celular Tumoral , Cognición/efectos de los fármacos , Modelos Animales de Enfermedad , Quimioterapia Combinada/métodos , Fragilidad/metabolismo , Hipocampo/metabolismo , Masculino , Ratones , Actividad Motora/efectos de los fármacos , Mioblastos/efectos de los fármacos , Mioblastos/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Resultado del Tratamiento
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