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2.
PLoS One ; 17(9): e0273098, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36107951

RESUMO

Naked mole-rats are a long-lived rodent species (current lifespan >37 years) and an increasingly popular biomedical model. Naked mole-rats exhibit neuroplasticity across their long lifespan. Previous studies have begun to investigate their neurogenic patterns. Here, we test the hypothesis that neuronal maturation is extended in this long-lived rodent. We characterize cell proliferation and neuronal maturation in established rodent neurogenic regions over 12 months following seven days of consecutive BrdU injection. Given that naked mole-rats are eusocial (high reproductive skew where only a few socially-dominant individuals reproduce), we also looked at proliferation in brain regions relevant to the social-decision making network. Finally, we measured co-expression of EdU (newly-born cells), DCX (immature neuron marker), and NeuN (mature neuron marker) to assess the timeline of neuronal maturation in adult naked mole-rats. This work reaffirms the subventricular zone as the main source of adult cell proliferation and suggests conservation of the rostral migratory stream in this species. Our profiling of socially-relevant brain regions suggests that future work which manipulates environmental context can unveil how newly-born cells integrate into circuitry and facilitate adult neuroplasticity. We also find naked mole-rat neuronal maturation sits at the intersection of rodents and long-lived, non-rodent species: while neurons can mature by 3 weeks (rodent-like), most neurons mature at 5 months and hippocampal neurogenic levels are low (like long-lived species). These data establish a timeline for future investigations of longevity- and socially-related manipulations of naked mole-rat adult neurogenesis.


Assuntos
Ratos-Toupeira , Neurogênese , Animais , Bromodesoxiuridina , Longevidade/fisiologia , Ratos-Toupeira/fisiologia , Neurônios/fisiologia
3.
Nutrients ; 14(17)2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36079924

RESUMO

Hyperglycemia is one of the important causes of neurodegenerative disorders and aging. Aquilaria crassna Pierre ex Lec (AC) has been widely used to relieve various health ailments. However, the neuroprotective and anti-aging effects against high glucose induction have not been investigated. This study aimed to investigate the effects of hexane extract of AC leaves (ACH) in vitro using human neuroblastoma SH-SY5Y cells and in vivo using nematode Caenorhabditis elegans. SH-SY5Y cells and C. elegans were pre-exposed with high glucose, followed by ACH treatment. To investigate neuroprotective activities, neurite outgrowth and cell cycle progression were determined in SH-SY5Y cells. In addition, C. elegans was used to determine ACH effects on antioxidant activity, longevity, and healthspan. In addition, ACH phytochemicals were analyzed and the possible active compounds were identified using a molecular docking study. ACH exerted neuroprotective effects by inducing neurite outgrowth via upregulating growth-associated protein 43 and teneurin-4 expression and normalizing cell cycle progression through the regulation of cyclin D1 and SIRT1 expression. Furthermore, ACH prolonged lifespan, improved body size, body length, and brood size, and reduced intracellular ROS accumulation in high glucose-induced C. elegans via the activation of gene expression in the DAF-16/FoxO pathway. Finally, phytochemicals of ACH were analyzed and revealed that ß-sitosterol and stigmasterol were the possible active constituents in inhibiting insulin-like growth factor 1 receptor (IGFR). The results of this study establish ACH as an alternative medicine to defend against high glucose effects on neurotoxicity and aging.


Assuntos
Caenorhabditis elegans , Extratos Vegetais , Thymelaeaceae , Animais , Caenorhabditis elegans/efeitos dos fármacos , Linhagem Celular Tumoral , Fatores de Transcrição Forkhead/metabolismo , Glucose/efeitos adversos , Humanos , Longevidade , Simulação de Acoplamento Molecular , Extratos Vegetais/química , Thymelaeaceae/química
4.
Sci Adv ; 8(37): eabo5482, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36112674

RESUMO

Development is tightly connected to aging, but whether pharmacologically targeting development can extend life remains unknown. Here, we subjected genetically diverse UMHET3 mice to rapamycin for the first 45 days of life. The mice grew slower and remained smaller than controls for their entire lives. Their reproductive age was delayed without affecting offspring numbers. The treatment was sufficient to extend the median life span by 10%, with the strongest effect in males, and helped to preserve health as measured by frailty index scores, gait speed, and glucose and insulin tolerance tests. Mechanistically, the liver transcriptome and epigenome of treated mice were younger at the completion of treatment. Analogous to mice, rapamycin exposure during development robustly extended the life span of Daphnia magna and reduced its body size. Overall, the results demonstrate that short-term rapamycin treatment during development is a novel longevity intervention that acts by slowing down development and aging, suggesting that aging may be targeted already early in life.


Assuntos
Insulinas , Longevidade , Animais , Daphnia/genética , Glucose , Masculino , Camundongos , Sirolimo/farmacologia
5.
Science ; 377(6610): 1092-1099, 2022 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-36048960

RESUMO

In most organisms, reproduction is correlated with shorter life span. However, the reproductive queen in eusocial insects exhibits a much longer life span than that of workers. In Harpegnathos ants, when the queen dies, workers can undergo an adult caste switch to reproductive pseudo-queens (gamergates), exhibiting a five-times prolonged life span. To explore the relation between reproduction and longevity, we compared gene expression during caste switching. Insulin expression is increased in the gamergate brain that correlates with increased lipid synthesis and production of vitellogenin in the fat body, both transported to the egg. This results from activation of the mitogen-activated protein kinase (MAPK) branch of the insulin signaling pathway. By contrast, the production in the gamergate developing ovary of anti-insulin Imp-L2 leads to decreased signaling of the AKT/forkhead box O (FOXO) branch in the fat body, which is consistent with their extended longevity.


Assuntos
Formigas , Insulina , Longevidade , Reprodução , Animais , Formigas/metabolismo , Feminino , Insulina/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Ovário/crescimento & desenvolvimento , Transdução de Sinais , Vitelogeninas/biossíntese
6.
Med Sci (Paris) ; 38(8-9): 723-725, 2022.
Artigo em Francês | MEDLINE | ID: mdl-36094245

RESUMO

New approaches allow precise measurement of somatic mutations in tissues. Applied to a diverse set of mammals, these methods show that somatic mutation load increases with age (as expected) but reaches similar levels near the end of life for animals with extremely different longevity. This is an important result that has many repercussions on concepts of aging and of evolution of longevity.


Assuntos
Envelhecimento , Longevidade , Envelhecimento/genética , Animais , Longevidade/genética , Mamíferos , Mutação
9.
Immunity ; 55(9): 1583-1585, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36103855

RESUMO

Caloric restriction (CR) reduces inflammation and the incidence of chronic diseases, thereby extending healthspan and lifespan. In this issue of Immunity, Ryu et al. (2022) propose that reduction of SPARC, a matricellular protein, during CR offers beneficial effects by reducing SPARC-driven inflammatory phenotypes in macrophages.


Assuntos
Restrição Calórica , Longevidade , Humanos , Inflamação , Osteonectina/genética
10.
Development ; 149(18)2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36052696

RESUMO

Trim33 (Tif1γ) is a transcriptional regulator that is notably involved in several aspects of hematopoiesis. It is essential for the production of erythrocytes in zebrafish, and for the proper functioning and aging of hematopoietic stem and progenitor cells (HSPCs) in mice. Here, we have found that, in zebrafish development, Trim33 is essential cell-autonomously for the lifespan of the yolk sac-derived primitive macrophages, as well as for the initial production of definitive (HSPC-derived) macrophages in the first niche of definitive hematopoiesis, the caudal hematopoietic tissue. Moreover, Trim33 deficiency leads to an excess production of definitive neutrophils and thrombocytes. Our data indicate that Trim33 radically conditions the differentiation output of aorta-derived HSPCs in all four erythro-myeloid cell types, in a niche-specific manner.


Assuntos
Longevidade , Peixe-Zebra , Animais , Hematopoese , Células-Tronco Hematopoéticas , Macrófagos/metabolismo , Camundongos , Fatores de Transcrição/metabolismo
11.
Int J Mol Sci ; 23(17)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36077358

RESUMO

Globally, better health care access and social conditions ensured a significant increase in the life expectancy of the population. There is, however, a clear increase in the incidence of age-related diseases which, besides affecting the social and economic sustainability of countries and regions around the globe, leads to a decrease in the individual's quality of life. There is an urgent need for interventions that can reverse, or at least prevent and delay, the age-associated pathological deterioration. Within this line, this narrative review aims to assess updated evidence that explores the potential therapeutic targets that can mimic or complement the recognized anti-aging effects of physical exercise. We considered pertinent to review the anti-aging effects of the following drugs and supplements: Rapamycin and Rapamycin analogues (Rapalogs); Metformin; 2-deoxy-D-glucose; Somatostatin analogues; Pegvisomant; Trametinib; Spermidine; Fisetin; Quercetin; Navitoclax; TA-65; Resveratrol; Melatonin; Curcumin; Rhodiola rosea and Caffeine. The current scientific evidence on the anti-aging effect of these drugs and supplements is still scarce and no recommendation of their generalized use can be made at this stage. Further studies are warranted to determine which therapies display a geroprotective effect and are capable of emulating the benefits of physical exercise.


Assuntos
Longevidade , Qualidade de Vida , Exercício Físico , Sirolimo/farmacologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-36078731

RESUMO

In 2021, the Toronto Metropolitan University Institute for Stress and Wellbeing Research welcomed over 200 conference delegates across Canada to the inaugural Canadian Stress Research Summit (CSRS) to share ideas and foster collaboration among Canadian scholars. This conference was unique from existing international stress-related conferences as it bridged science and community. The objective of this conference report is to provide an overview of the 3-day virtual inaugural stress conference, offering a summary of the keynote addresses, themed symposia, spotlight presentations, graphical designs of selected presentations, and conference feedback. Overall, the CSRS highlighted important methodological considerations in understanding the relationship between stress exposure and various outcomes of interest that pertain to the mental health and wellbeing of Canadians. Furthermore, there is a need for continued work to understand stress across the lifespan from an inclusive and diverse Canadian lens.


Assuntos
Longevidade , Canadá , Humanos
13.
Radiat Prot Dosimetry ; 198(13-15): 1160-1164, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36083765

RESUMO

The authors performed a combined analysis using the data obtained from continuous low dose rate irradiation experiments on mice conducted at the Institute for Environmental Sciences, namely, cancer incidence data and lifespan data. They estimated the length of cancer progression period, which is difficult to assess experimentally. The combined analysis showed that the mean cancer progression period is 173 d in the control group and 103 d in the irradiated group.


Assuntos
Longevidade , Neoplasias Induzidas por Radiação , Relação Dose-Resposta à Radiação , Humanos , Incidência , Longevidade/efeitos da radiação , Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias Induzidas por Radiação/etiologia
14.
Sci Rep ; 12(1): 15245, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36085160

RESUMO

The mosquito Aedes aegypti is the primary vector of a range of medically important viruses including dengue, Zika, West Nile, yellow fever, and chikungunya viruses. The endosymbiotic bacterium Wolbachia pipientis wAlbB strain is a promising biocontrol agent for blocking viral transmission by Ae. aegypti. To predict the long-term efficacy of field applications, a thorough understanding of the interactions between symbiont, host, and pathogen is required. Wolbachia influences host physiology in a variety of ways including reproduction, immunity, metabolism, and longevity. MicroRNAs (miRNAs) are highly conserved small non-coding RNAs that regulate gene expression in eukaryotes and viruses. Several miRNAs are known to regulate biological processes in Drosophila and mosquitoes, including facilitating Wolbachia maintenance. We generated the first chromosomal map of Ae. aegypti miRNAs, and compared miRNA expression profiles between a wAlbB-transinfected Ae. aegypti mosquito line and a tetracycline cleared derivative, using deep small RNA-sequencing. We found limited modulation of miRNAs in response to wAlbB infection. Several miRNAs were modulated in response to age, some of which showed greater upregulation in wAlbB-infected mosquitoes than in tetracycline cleared ones. By selectively inhibiting some differentially expressed miRNAs, we identified miR-2946-3p and miR-317-3p as effecting mosquito longevity in Wolbachia-infected mosquitoes.


Assuntos
Aedes , MicroRNAs , Wolbachia , Infecção por Zika virus , Zika virus , Aedes/genética , Animais , Antibacterianos , Drosophila , Longevidade/genética , MicroRNAs/genética , Mosquitos Vetores , Tetraciclina
15.
PLoS One ; 17(9): e0274214, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36054207

RESUMO

Obesity continues to be a significant global health issue and contributes to a variety of comorbidities and disease states. Importantly, obesity contributes to adverse cardiovascular health outcomes, which is the leading cause of death worldwide. Further, maternal obesity during gestation has been shown to predispose offspring to adverse phenotypic outcomes, specifically cardiovascular outcomes. Therefore, we hypothesized that diet-induced obesity during gestation would result in adverse cardiovascular phenotypes in first-generation offspring that would have functional consequences in juvenile and advanced ages. Multiparous Rambouillet/Columbia cross ewes (F0) were fed a highly palatable, pelleted diet at either 100% (CON), or 150% (OB) of National Research Council recommendations from 60 days prior to conception, until necropsy at d 135 (90%) of gestation (CON: n = 5, OB: n = 6), or through term for lambs (F1: 2.5 mo. old; CON: n = 9, OB: n = 6) and ewes (F1:9 years old; CON: n = 5, OB: n = 8). Paraffin-embedded fetal aorta section staining revealed increased collagen:elastin ratio and greater aortic wall thickness in OBF1 fetuses. Invasive auricular blood pressure recordings revealed elevated systolic blood pressure in OBF1 lambs, but no differences in diastolic pressure. In aged F1 ewes, systolic and diastolic blood pressures were reduced in OBF1 relative to CONF1. Echocardiography revealed no treatment differences in F1 lambs, but F1 ewes show tendencies for increased end systolic volume and decreased stroke volume, and markedly reduced ejection fraction. Therefore, we conclude that maternal obesity programs altered cardiovascular development that results in a hypertensive state in OBF1 lambs. Increased cardiac workload resulting from early life hypertension precedes the failure of the heart to maintain function later in life.


Assuntos
Fenômenos Fisiológicos da Nutrição Materna , Obesidade Materna , Animais , Dieta/veterinária , Feminino , Humanos , Longevidade , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Obesidade , Gravidez , Ovinos
16.
Mol Biol Evol ; 39(9)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36065792

RESUMO

Sirtuins are a family of proteins that protect against cellular injury and aging; understanding their evolution should reveal fundamental mechanisms governing longevity. "Early-branching" animals such as sea sponges and jellyfish have been understudied in previous analyses of sirtuin diversity. These organisms not only hold important positions at the base of the evolutionary tree, but also have unique aging dynamics that defy convention, such as quasi-immortality and high regenerative capacity. In this study, we survey the evolution of sirtuin proteins in animals, with a focus on the oldest living lineages. We describe previously unrecognized expansions of "Class IV" and "Class I" sirtuins around the origin of animals, raising the number of sirtuin families in the last common ancestor to at least nine. Most of these undescribed sirtuins have been lost in vertebrates and other bilaterian animals. Our work also clarifies the evolution of PNC1 and NAMPT enzymes that carry out the rate-limiting step in sirtuin-related NAD+ biosynthesis. The genes for PNC1 and NAMPT enzymes were both present in the first animals, with the genes being lost a minimum of 11 and 13 times, respectively, over the course of animal evolution. We propose that species with these ancestral gene repertoires are ideal model organisms for studying the genetic regulation of animal longevity and will provide clues to increasing longevity in humans.


Assuntos
Sirtuínas , Envelhecimento , Animais , Humanos , Longevidade/genética , NAD , Sirtuínas/genética , Sirtuínas/metabolismo , Vertebrados/metabolismo
17.
Gene ; 845: 146776, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36063972

RESUMO

Mutations in the mitochondrial DNA (mtDNA) are closely related to age and age-related complex diseases, but the exact regulatory mechanism of mtDNA natural variation or polymorphism and ageing remains unclear. Recently, nuclear genes that regulate mitochondrial functions and thereby influence ageing have been widely studied. In this study, the relationship between the retrograde communication from the mitochondria to the nucleus and its ultimate effect on ageing has been elucidated. This study found that the natural variations in COX1 of the mitochondria in the Caenorhabditis elegans population do not correlate with multiple phenotypes, except for a mild correlation with lifespan. After excluding the differences in the nuclear genome, the correlation between natural mitochondrial variation and lifespan increased significantly. Moreover, mtDNA variation downregulated the nuclear dct-15 gene expression, which consequently reduced the lifespan, development rate and motility of C. elegans. dct-15 mutations decreased mitochondria copy number but increased ATP content and mitochondrial ultrastructure. Thus, the results indicated that dct-15 interacted with the mitochondrial DNA polymorphisms in COX1 and is associated with ageing. Finally, bioinformatic analyses revealed that mtDNA variation regulated the structural constituent of the cuticle via dct-15 and suggested that the structural constituent of the cuticle could have an important role in the development and ageing processes. These results provide insights into the mtDNA mechanism that can alter the nuclear gene and thereby regulate ageing and ageing-related diseases.


Assuntos
Caenorhabditis elegans , DNA Mitocondrial , Trifosfato de Adenosina/metabolismo , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Longevidade/genética , Mitocôndrias/genética , Mitocôndrias/metabolismo
19.
Proc Biol Sci ; 289(1982): 20220868, 2022 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-36069016

RESUMO

Parental stress often has long-term consequences for offspring. However, the mechanisms underlying these effects and how they are shaped by conditions offspring subsequently experience are poorly understood. Telomeres, which often shorten in response to stress and predict longevity, may contribute to, and/or reflect these cross-generational effects. Traditionally, parental stress is expected to have negative effects on offspring telomeres, but experimental studies in captive animals suggest that these effects may depend on the subsequent conditions that offspring experience. Yet, the degree to which parental stress influences and interacts with stress experienced by offspring to affect offspring telomeres and survival in free-living organisms is unknown. To assess this, we experimentally manipulated the stress exposure of free-living parent and offspring house sparrows (Passer domesticus). We found a weak, initial, negative effect of parental stress on offspring telomeres, but this effect was no longer evident at the end of post-natal development. Instead, the effects of parental stress depended on the natural sources of stress that offspring experienced during post-natal development whereby some outcomes were improved under more stressful rearing conditions. Thus, the effects of parental stress on offspring telomeres and survival are context-dependent and may involve compensatory mechanisms of potential benefit under some circumstances.


Assuntos
Pardais , Animais , Longevidade , Pardais/fisiologia , Telômero
20.
Biogerontology ; 23(5): 541-557, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36048312

RESUMO

Life expectancy in Western countries is increasing, with concomitant rise in ageing-related pathologies, including Parkinson's and Alzheimer's disease, as well as other neurodegenerative diseases. Consequently, the medical, psychological and economic burden to society is increasing. Thus, understanding the cellular and molecular mechanisms underlying the association of ageing with elevated vulnerability to disease is crucial towards promoting quality of life in old age. Caenorhabditis elegans has emerged as a versatile model to study ageing, due to its simplicity, fast life cycle, and the availability of a wide range of biological tools to target specific genes and cells. Indeed, recent studies in C. elegans have revealed that lipid metabolism plays a key role in controlling longevity by impinging on a plethora of molecular pathways and cell types. Here, we summarise findings relevant to the interplay between lipid metabolism and ageing in C. elegans, and discuss the implications for the pathogenesis of age-related disorders in humans.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Envelhecimento/metabolismo , Animais , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Humanos , Metabolismo dos Lipídeos , Longevidade/genética , Qualidade de Vida
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