lifespan Dotaz Zobrazit nápovědu
12, 324 s. : il., tab.
- Konspekt
- Fyziologie člověka a srovnávací fyziologie
- NLK Obory
- fyziologie
- biologie
sv.
- MeSH
- dlouhověkost MeSH
- geriatrie MeSH
- naděje dožití MeSH
- Publikační typ
- periodika MeSH
To uncover the selective forces shaping life-history trait evolution across species, we investigate the genomic basis underlying adaptations to seasonal habitat desiccation in African killifishes, identifying the genetic variants associated with positive and relaxed purifying selection in 45 killifish species and 231 wild individuals distributed throughout sub-Saharan Africa. In annual species, genetic drift led to the expansion of nuclear and mitochondrial genomes and caused the accumulation of deleterious genetic variants in key life-history modulating genes such as mtor, insr, ampk, foxo3, and polg. Relaxation of purifying selection is also significantly associated with mitochondrial function and aging in human populations. We find that relaxation of purifying selection prominently shapes genomes and is a prime candidate force molding the evolution of lifespan and the distribution of genetic variants associated with late-onset diseases in different species. VIDEO ABSTRACT.
- MeSH
- Cyprinodontidae klasifikace genetika MeSH
- dlouhověkost * MeSH
- frekvence genu MeSH
- fylogeneze MeSH
- fylogeografie MeSH
- genom mitochondriální MeSH
- mitochondrie genetika metabolismus MeSH
- molekulární evoluce MeSH
- mutace MeSH
- replikace DNA MeSH
- selekce (genetika) * MeSH
- stárnutí MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND/AIMS: The ewe is increasingly being used as an animal model for pelvic floor disorders. The aim was to further characterize changes in the vaginal properties during its entire lifespan. METHODS: Vaginal tissues were collected at different stages of reproductive life (neonatal, prepubescence, nulliparous, primiparous, multiparous, and menopausal; ≥6 ewes/group). Vaginal size, as well as active and passive biomechanics, was measured. Microscopy included thickness of glycogen, epithelium, lamina propria and muscularis thickness, densities of collagen, elastin, smooth muscle, and nerves. RESULTS: Vaginal dimensions increase during adolescence, peak at reproductive levels, and decrease sharply after ovariectomy. One year after first delivery, the distal vagina gets more compliant, yet this is reversed later in life. The thickness of glycogen staining epithelial layers changed with puberty and menopause. The epithelium was markedly thicker after multiple deliveries. The thickness of lamina propria and muscularis increased in puberty and in nulliparous. Semi-quantitative collagen assessment demonstrated a lower collagen and higher elastin content after first and multiple deliveries. CONCLUSION: The changes in the ovine vaginal wall during representative moments of her lifespan parallel those observed in women.
- MeSH
- dlouhověkost fyziologie MeSH
- menopauza fyziologie MeSH
- modely u zvířat MeSH
- ovarektomie MeSH
- ovce MeSH
- parita fyziologie MeSH
- rozmnožování fyziologie MeSH
- těhotenství MeSH
- vagina anatomie a histologie fyziologie MeSH
- zvířata MeSH
- Check Tag
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
In natural populations, individuals experience daily fluctuations in environmental conditions that synchronise endogenous biorhythms. Artificial alterations of environmental fluctuations can have negative consequences for life history traits, including lifespan. In laboratory studies of aging, the role of fluctuating temperature is usually overlooked and we know little of how thermal fluctuation modulates senescence in vertebrates. In this longitudinal study we followed individually-housed turquoise killifish, Nothobranchius furzeri, from two thermal regimes; ecologically relevant diel fluctuations (20 °C - 35 °C) and stable temperature (27.5 °C), and compared their survival, growth and reproduction. Fish experiencing fluctuating temperatures had a longer median lifespan but reached smaller asymptotic body size. Within-treatment variation indicated that extended lifespan in fluctuating temperatures was not causally linked to decreased growth rate or smaller body size, but occurred solely due to the effect of thermal fluctuations. Male body size was positively associated with lifespan in stable temperatures but this relationship was disrupted in fluctuating thermal regimes. Females exposed to fluctuating temperatures effectively compensated egg production for their smaller size. Thus, there was no difference in absolute fecundity between thermal regimes and body-size corrected fecundity was higher in females in fluctuating temperatures. Overall, despite a brief exposure to sub-optimal thermal conditions during fluctuations, fluctuating temperature had a positive effect on survival and reproduction. These results suggest that the expression of life history traits and their associations under stable temperatures are a poor representation of the relationships obtained from ecologically relevant thermal fluctuations.
- MeSH
- dlouhověkost MeSH
- Fundulidae * MeSH
- lidé MeSH
- longitudinální studie MeSH
- rozmnožování MeSH
- teplota MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
We provide here normative values of yearly percentage brain volume change (PBVC/y) as obtained with Structural Imaging Evaluation, using Normalization, of Atrophy, a widely used open-source software, developing a PBVC/y calculator for assessing the deviation from the expected PBVC/y in patients with neurological disorders. We assessed multicenter (34 centers, 11 acquisition protocols) magnetic resonance imaging data of 720 healthy participants covering the whole adult lifespan (16-90 years). Data of 421 participants with a follow-up > 6 months were used to obtain the normative values for PBVC/y and data of 392 participants with a follow-up <1 month were selected to assess the intrasubject variability of the brain volume measurement. A mixed model evaluated PBVC/y dependence on age, sex, and magnetic resonance imaging parameters (scan vendor and magnetic field strength). PBVC/y was associated with age (p < 0.001), with 60- to 70-year-old participants showing twice more volume decrease than participants aged 30-40 years. PBVC/y was also associated with magnetic field strength, with higher decreases when measured by 1.5T than 3T scanners (p < 0.001). The variability of PBVC/y normative percentiles was narrower as the interscan interval was longer (e.g., 80th normative percentile was 50% smaller for participants with 2-year than with 1-year follow-up). The use of these normative data, eased by the freely available calculator, might help in better discriminating pathological from physiological conditions in the clinical setting.
- MeSH
- atrofie MeSH
- difuzní magnetická rezonance MeSH
- dlouhověkost * MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mozek diagnostické zobrazování patologie MeSH
- multicentrické studie jako téma MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stárnutí patologie MeSH
- velikost orgánu MeSH
- zobrazování trojrozměrné MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in both adults and children. Along with obesity and metabolic syndrome, genetic predisposition influences the progression of NAFLD. Here, we investigated the effect of lifespan/healthspan-related single nucleotide polymorphisms (SNPs) on metabolically associated fatty liver disease in children. METHODS: We evaluated the impact of 10 SNPs involved in both human liver/metabolic diseases and healthspan (interleukin-6 [IL-6] rs1800795, antisense non coding RNA in the INK4 locus (ANRIL) rs1556516, SH2B3/ATXN2 rs7137828, FURIN rs17514846, TP53 rs1042522, APOC3 rs2542052, KL rs9536314, KL rs9527025, SIRT6 rs107251, FOXO3 rs2802292) on NAFLD-related metabolic and liver features in 177 pediatric patients with biopsy-proven NAFLD, by comparing them to 146 healthy controls. We then applied a multidimensional reduction (MDR) case-control analysis of SNP-SNP interactions, to identify the joint effect of analyzed SNPs in predicting NAFLD and associated features. RESULTS: Discrete SNPs were significantly associated with individual metabolic NAFLD features, but none of them significantly associated with NAFLD diagnosis. By testing potential synergies using the MDR approach, the best combination to diagnose NAFLD (P = 0.0011) resulted in the one encompassing IL-6 rs1800795 and ANRIL rs1556516. Consistently, the risk combinations suggested by SNP-SNP analysis strongly associated with a higher level of fasting plasma blood glucose level (P = 0.024). CONCLUSION: In conclusion, here we demonstrated a synergic interaction between IL-6 rs1800795 and ANRIL rs1556516 in the diagnosis of NAFLD, and NAFLD-associated hyperglycemia in children. Larger studies are required to confirm our findings and to elucidate mechanisms by which the genetic interaction between these two genes influences healthspan in pediatric NAFLD.
- MeSH
- dítě MeSH
- dlouhověkost MeSH
- dospělí MeSH
- genetická predispozice k nemoci MeSH
- játra MeSH
- jednonukleotidový polymorfismus MeSH
- lidé MeSH
- nealkoholová steatóza jater * genetika MeSH
- sirtuiny * MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Diet-induced obesity is a major risk factor for metabolic syndrome, diabetes and cardiovascular disease. Here, we show that a 5-d fasting-mimicking diet (FMD), administered every 4 weeks for a period of 2 years, ameliorates the detrimental changes caused by consumption of a high-fat, high-calorie diet (HFCD) in female mice. We demonstrate that monthly FMD cycles inhibit HFCD-mediated obesity by reducing the accumulation of visceral and subcutaneous fat without causing loss of lean body mass. FMD cycles increase cardiac vascularity and function and resistance to cardiotoxins, prevent HFCD-dependent hyperglycaemia, hypercholesterolaemia and hyperleptinaemia and ameliorate impaired glucose and insulin tolerance. The effect of monthly FMD cycles on gene expression associated with mitochondrial metabolism and biogenesis in adipocytes and the sustained ketogenesis in HFCD-fed mice indicate a role for fat cell reprogramming in obesity prevention. These effects of an FMD on adiposity and cardiac ageing could explain the protection from HFCD-dependent early mortality.
- MeSH
- dieta s vysokým obsahem tuků * MeSH
- dlouhověkost * MeSH
- kardiovaskulární nemoci metabolismus patologie MeSH
- metabolické nemoci metabolismus patologie MeSH
- myši MeSH
- omezení příjmu potravy * MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, N.I.H., Intramural MeSH