Age-related Disturbances Research Articles

Abstract Mo107: Age-Related Impairment of Mitochondrial Protein Turnover Exacerbates Pathogenesis of Heart Failure with Preserved Ejection Fraction in Old Mice

Introduction: Age is recognized as a major risk factor for heart failure with preserved ejection fraction (HFpEF), yet the precise role of aging in HFpEF development remains unknown. Disruption of mitochondrial protein turnover affects the quality and quantity of proteins crucial for energy metabolism. Although mitochondrial dysfunction is a key feature of both aging and HFpEF heart, the influence of age-related disturbances in mitochondrial protein turnover on HFpEF pathogenesis remains unclear. Hypothesis: Age-related impairment of mitochondrial protein turnover intensifies proteostatic perturbations induced by hypertensive and metabolic stress (2-hit stress) to exacerbate pathogenesis of cardiometabolic HFpEF. Methods: Young (3 mo.) and old (19 mo.) C57BL/6J male mice were exposed to high-fat diet and L-NAME to induce HFpEF development. Deuterium oxide (D 2 O) labeling coupled with mass spectrometry was used to investigate bulk and individual mitochondrial protein synthesis. The changes in individual mitochondrial protein abundance and protein degradation pathways were also studied. Results: Old mice presented exacerbated HFpEF characteristics compared to young mice, with higher mortality and worsened cardiac and extra-cardiac phenotypes. Regardless of age, mice subjected to 2-hit stress had 24% higher bulk mitochondrial protein synthesis compared to controls. Old control and HFpEF mice showed 17% lower mitochondrial protein synthesis compared to younger counterparts, potentially hindering the replacement of dysfunctional mitochondrial proteins. Aging reduced the synthesis rates of 30 out of 115 proteins synthesized more rapidly with HFpEF, including those involved in mitochondrial metabolism. Despite slower synthesis of numerous mitochondrial proteins with age, the overall abundance of these proteins remained unchanged or elevated compared to young counterparts, indicating impaired protein degradation. We found that aging and 2-hit stress differentially inhibited degradation pathways, including autophagy and the ubiquitin-proteasome system, further impairing protein turnover. Conclusion: Aging impairs mitochondrial protein turnover in cardiometabolic HFpEF and contributes to poorer disease outcomes.

Effect of a water-soluble form of dihydroquercetin on age-dependent LPS-induced gliovascular remodeling of the substantia nigra in rats

Background. The molecular and cellular mechanisms of action of the water-soluble form of dihydroquercetin (DHA-VF) on neurogliovascular units, age-related disturbances of intrasystem connections that may underlie neuroinflammatory and neurodegenerative diseases, remain unclear.The aim: to study structural changes of microcirculatory vessels and functional responses of micro- and astroglial cells in the substantia nigra of young and old rats in response to intranigral injection of lipopolysaccharide (LPS) and subsequent oral administration of DHA-VF.Methods. Young (250-320 g) and old (390-450 g) Wistar rats were injected with 2 μL LPS solution at a concentration of 0.01 μL/mL (experimental group; n=24) or 2 μL sterile physiological solution (control group; n=12) into the substantia nigra area of the brain using a stereotaxic device. Half of the animals in the experimental groups (6 animals of each age group) were given 2 ml of a solution containing DHA-VF at a concentration of 3 mg/mL daily by gavage with a probe. After 8 weeks, the animals were decapitated and cryostat sections were obtained for histochemical (FITC-labeled tomato lectin) and immunohistochemical (antibodies against GFAP and CD-11β) staining of vascular endothelium and glial cells, respectively. Results. 8 weeks after LPS administration to old rats in the CS, a significant excess of areas occupied by cell bodies and processes of microglial and astroglial cells as well as the number of vessels at standard sites was found compared to both young animals exposed to similar exposure and old control animals. Oral administration of DHA-VF to rats significantly reduced LPS-induced glial activation in young and old animals. In addition, administration of DHA-VF to old animals reduced the intensity of LPS-induced microvascular remodeling of the CS. Conclusions. LPS administration in the rat CS induces neuroinflammation and vascular angiogenesis, which are maximally expressed in old animals. Administration of DHA-VF for 8 weeks significantly reduced these LPS-induced changes.

Anti-aging mechanism of different age donor-matched adipose-derived stem cells

BackgroundAdipose-derived stem cells (ASCs) have anti-aging and anti-obesity effects in aged animals, but the underlying molecular mechanism remains unknown.MethodsIn the present study, we evaluated the in vivo transplantation effects of different age donor-matched ASCs on natural aging and leptin knockout mice (ob−/ob− mice). The multi-omics expression profiles of young and aged mouse donor-derived ASCs were also analyzed.ResultsThe results revealed that ASCs from young donors induced weight and abdominal fat loss for older recipients but not for young or ob−/ob−mice. The young and aged mouse donor ASCs displayed significant phenotypic differences, contributing to the distinguished weight loss and anti-aging effects in aged mice.ConclusionsOur data suggest an underlying molecular mechanism by which young-donor ASCs reduce immune cells and inflammation in aged mice via secreted immune factors. These findings point to a general anti-aging mechanism of stem cells, which may provide new insights into age-related disturbances of stem cell plasticity in healthy aging and age-related diseases.

Gait disturbances and muscle dysfunction in fibroblast growth factor 2 knockout mice

Fibroblast growth factor 2 (FGF2) is important in musculoskeletal homeostasis, therefore the impact of reduction or Fgf2 knockout on skeletal muscle function and phenotype was determined. Gait analysis as well as muscle strength testing in young and old WT and Fgf2KO demonstrated age-related gait disturbances and reduction in muscle strength that were exacerbated in the KO condition. Fgf2 mRNA and protein were significantly decreased in skeletal muscle of old WT compared with young WT. Muscle fiber cross-sectional area was significantly reduced with increased fibrosis and inflammatory infiltrates in old WT and Fgf2KO vs. young WT. Inflammatory cells were further significantly increased in old Fgf2KO compared with old WT. Lipid-related genes and intramuscular fat was increased in old WT and old Fgf2KO with a further increase in fibro-adipocytes in old Fgf2KO compared with old WT. Impaired FGF signaling including Increased β-Klotho, Fgf21 mRNA, FGF21 protein, phosphorylated FGF receptors 1 and 3, was observed in old WT and old Fgf2KO. MAPK/ ERK1/2 was significantly increased in young and old Fgf2KO. We conclude that Fgf2KO, age-related decreased FGF2 in WT mice, and increased FGF21 in the setting of impaired Fgf2 expression likely contribute to impaired skeletal muscle function and sarcopenia in mice.

Bright Light Therapy and Circadian Cycles in Institutionalized Elders.

BackgroundBright light therapy has been found to be an efficient method to improve the main parameters of circadian rhythms. However, institutionalized elders may suffer reduced exposure to diurnal light, which may impair their circadian rhythms, cognitive performance, and general health status.ObjectivesTo analyze the effects of 5 days of morning exposure for 90 min to bright light therapy (BLT) applied to institutionalized elderly subjects with mild/moderate cognitive impairment.SubjectsThirty-seven institutionalized subjects of both sexes, aged 70–93 years.MethodsThe study lasted three consecutive weeks. During the second week the subjects were submitted to BLT (7000–10,000 lux at eye level) on a daily basis. Cognition, attention, and sleep quality were evaluated at the beginning of the first and third week. Circadian variables were recorded continuously throughout the 3 weeks. Non-invasive holders and validated tests were used to analyze the variables studied.ResultsAfter BLT we have found significant improvements in general cognitive capabilities, sleep quality and in the main parameters of the subject’s circadian rhythms. The results show that merely 90 min of BLT for five days seems to achieve a significant improvement in a constellation of circadian, sleep, health, and cognitive factors.ConclusionBright light therapy is an affordable, effective, fast-acting therapy for age-related disturbances, with many advantages over pharmacological alternatives. We hypothesize these effects were the result of activating the residual activity of their presumably weakened circadian system.

Age-related Disturbances in DNA (hydroxy)methylation in APP/PS1 Mice.

Brain aging has been associated with aberrant DNA methylation patterns, and changes in the levels of DNA methylation and associated markers have been observed in the brains of Alzheimer’s disease (AD) patients. DNA hydroxymethylation, however, has been sparsely investigated in aging and AD. We have previously reported robust decreases in 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in the hippocampus of AD patients compared to non-demented controls. In the present study, we investigated 3- and 9-month-old APPswe/PS1ΔE9 transgenic and wild-type mice for possible age-related alterations in 5-mC and 5-hmC levels in three hippocampal sub-regions using quantitative immunohistochemistry. While age-related increases in levels of both 5-mC and 5-hmC were found in wild-type mice, APPswe/PS1ΔE9 mice showed decreased levels of 5-mC at 9 months of age and no age-related changes in 5-hmC throughout the hippocampus. Altogether, these findings suggest that aberrant amyloid processing impact on the balance between DNA methylation and hydroxymethylation in the hippocampus during aging in mice.

Long Non-Coding RNAs in Neuronal Aging.

The expansion of long non-coding RNAs (lncRNAs) in organismal genomes has been associated with the emergence of sophisticated regulatory networks that may have contributed to more complex neuronal processes, such as higher-order cognition. In line with the important roles of lncRNAs in the normal functioning of the human brain, dysregulation of lncRNA expression has been implicated in aging and age-related neurodegenerative disorders. In this paper, we discuss the function and expression of known neuronal-associated lncRNAs, their impact on epigenetic changes, the contribution of transposable elements to lncRNA expression, and the implication of lncRNAs in maintaining the 3D nuclear architecture in neurons. Moreover, we discuss how the complex molecular processes that are orchestrated by lncRNAs in the aged brain may contribute to neuronal pathogenesis by promoting protein aggregation and neurodegeneration. Finally, this review explores the possibility that age-related disturbances of lncRNA expression change the genomic and epigenetic regulatory landscape of neurons, which may affect neuronal processes such as neurogenesis and synaptic plasticity.

Changes in walking in the elderly

The article addresses gait disturbances in the elderly. It emphasizes that the system that maintains the balance in resting conditions and gait is based on the hierarchical principle and its function depends on the maintenance of integration between vestibular, visual and somatosensory information as well as on cognitive functions. Walking depends on the integrity of frontal-subcortical neuronal circles that support regulatory functions. The main pathogenetic mechanisms of age-related disturbances of balance and gait are a decrease in the efficacy of spinal motorneurons activation caused by Ia-afferentation, a decrease in cortical activation and excitability of corticospinal pathways and in the intensity of intracortical inhibition. The causes of age-related changes in walking are not confined to a single system (e.g., one sensory modality) but have a multisystem character and are involved in many structures. The author analyses the results of recent studies that use functional neuroimaging methods.

Normalisation against Circadian and Age-Related Disturbances Enables Robust Detection of Gene Expression Changes in Liver of Aged Mice.

The expression of some genes is affected by age. To detect such age-related changes, their expression levels are related to constant marker genes. However, transcriptional noise increasing with advancing age renders difficult the identification of real age-related changes because it may affect the marker genes as well. Here, we report a selection procedure for genes appropriate to normalise the mouse liver transcriptome under various conditions including age. These genes were chosen from an initial set of 16 candidate genes defined based on a RNA-sequencing experiment and published literature. A subset of genes was selected based on rigorous statistical assessment of their variability using both RNA-sequencing and Nanostring hybridization experiments. The robustness of these marker genes was then verified by the analysis of 130 publicly available data sets using the mouse liver transcriptome. Altogether, a set of three genes, Atp5h, Gsk3β, and Sirt2 fulfilled our strict selection criteria in all assessments, while four more genes, Nono, Tprkb, Tspo, and Ttr passed all but one assessment and were included into the final set of marker genes to enhance robustness of normalisation against outliers. Using the geometric mean of expression of the genes to normalise Nanostring hybridization experiments we reliably identified age-related increases in the expression of Casein kinase 1δ and 1ϵ, and Sfpq, while the expression of the glucose transporter Glut2 decreased. The age-related changes were verified by real-time PCR and Western blot analysis. As conclusion, proper normalisation enhances the robustness of quantitative methods addressing age-related changes of a transcriptome.

Dietary nitrate improves age-related hypertension and metabolic abnormalities in rats via modulation of angiotensin II receptor signaling and inhibition of superoxide generation

Advanced age is associated with increased risk for cardiovascular disease and type 2 diabetes. A proposed central event is diminished amounts of nitric oxide (NO) due to reduced generation by endothelial NO synthase (eNOS) and increased oxidative stress. In addition, it is widely accepted that increased angiotensin II (ANG II) signaling is also implicated in the pathogenesis of endothelial dysfunction and hypertension by accelerating formation of reactive oxygen species. This study was designed to test the hypothesis that dietary nitrate supplementation could reduce blood pressure and improve glucose tolerance in aged rats, via attenuation of NADPH oxidase activity and ANG II receptor signaling.Dietary nitrate supplementation for two weeks reduced blood pressure (10–15mmHg) and improved glucose clearance in old, but not in young rats. These favorable effects were associated with increased insulin responses, reduced plasma creatinine as well as improved endothelial relaxation to acetylcholine and attenuated contractility to ANG II in resistance arteries. Mechanistically, nitrate reduced NADPH oxidase-mediated oxidative stress in the cardiovascular system and increased cGMP signaling. Finally, nitrate treatment in aged rats normalized the gene expression profile of ANG II receptors (AT1A, AT2, AT1A/AT2 ratio) in the renal and cardiovascular systems without altering plasma levels of renin or ANG II.Our results show that boosting the nitrate-nitrite-NO pathway can partly compensate for age-related disturbances in endogenous NO generation via inhibition of NADPH oxidase and modulation of ANG II receptor expression. These novel findings may have implications for nutrition-based preventive and therapeutic strategies against cardiovascular and metabolic diseases.

The link of inflammation and neurodegeneration in progressive multiple sclerosis

Progressive multiple sclerosis (MS) is characterized clinically by the accumulation of neurological disability without unequivocal recovery. Understanding the mechanisms that determine entering in this stage of the disease is a great challenge in order to identify potential therapeutic targets. Recent advances in defining more accurately the progressive phenotype of MS, have concluded that differences between primary and secondary progressive forms of disease are relatively quantitative rather than qualitative. In both cases, a large number of molecular and cellular events that might lead to neurodegeneration have been suggested. These include microglia activation, chronic oxidative injury, accumulation of mitochondrial damage in axons, age-related disturbances and dysfunctional axonal transport among others. Commonly, these pathological mechanisms have been considered as a result of inflammatory demyelination but a primary degenerative condition has also been argued. It is now clear that both events contribute to the progression of the disease, however their temporal sequence is still a matter of debate. A detailed knowledge of progressive MS pathogenesis will allow to develop effective treatments for both progression and symptom management that should be based on a combination of anti-inflammatory, regenerative and neuroprotective strategies. In this review, we summarize current data and recent hypothesis about pathological forces that drive progression of damage in MS, i.e. cumulative cortical demyelination and neurodegeneration as well as diffuse alterations (microglia activation, axonal injury and atrophy) throughout white and grey matter in the brain and spinal cord. Finally, we discuss the potential of the aforementioned proposed disease mechanisms with regard to developing suitable therapies to halt the progression in MS pathology.

1,3-Dinitrobenzene neurotoxicity – Passage effect in immortalized astrocytes

Age-related disturbances in astrocytic mitochondrial function are linked to loss of neuroprotection and decrements in neurological function. The immortalized rat neocortical astrocyte-derived cell line, DI-TNC1, provides a convenient model for the examination of cellular aging processes that are difficult to study in primary cell isolates from aged brain. Successive passages in culture may serve as a surrogate of aging in which time-dependent adaptation to culture conditions may result in altered responses to xenobiotic challenge. To investigate the hypothesis that astrocytic mitochondrial homeostatic function is decreased with time in culture, low passage DI-TNC1 astrocytes (LP; #2–8) and high passage DI-TNC1 astrocytes (HP; #17–28) were exposed to the mitochondrial neurotoxicant 1,3-dinitrobenzene (DNB). Cells were exposed in either monoculture or in co-culture with primary cortical neurons. Astrocyte mitochondrial membrane potential, morphology, ATP production and proliferation were monitored in monoculture, and the ability of DI-TNC1 cells to buffer K+-induced neuronal depolarization was examined in co-cultures. In HP DI-TNC1 cells, DNB exposure decreased proliferation, reduced mitochondrial membrane potential and significantly decreased mitochondrial form factor. Low passage DI-TNC1 cells effectively attenuated K+-induced neuronal depolarization in the presence of DNB whereas HP counterparts were unable to buffer K+ in DNB challenge. Following DNB challenge, LP DI-TNC1 cells exhibited greater viability in co-culture than HP. The data provide compelling evidence that there is an abrupt phenotypic change in DI-TNC1 cells between passage #9–16 that significantly diminishes the ability of DI-TNC1 cells to compensate for neurotoxic challenge and provide neuroprotective spatial buffering. Whether or not these functional changes have an in vivo analog in aging brain remains to be determined.

Diabetes Accelerates Age-Related Lipid Profile Disturbances in Cardiovascular Complications

Cardio Vascular Complications (CVC) are predominant problems both in ageing and diabetes. The present study focuses on the effect of human ageing and diabetes, with special reference to serum lipid profile levels during cardiovascular complications in two age groups namely, 45±5 years and 65±5 years independent of obesity hypertension and nephropathy. The serum samples of study and control group includes estimation of serum total cholesterol, serum triglycerides, HDL-C, LDL-C and VLDL-C. Results shows, that the changes in the levels of lipid parameters follow a near similar trend in the two non-diabetic age groups with cardiovascular complications. Except the HDL-C which decline, total cholesterol, LDL-C, VLDL and triglycerides increases.

Young capillary vessels rejuvenate aged pancreatic islets.

Pancreatic islets secrete hormones that play a key role in regulating blood glucose levels (glycemia). Age-dependent impairment of islet function and concomitant dysregulation of glycemia are major health threats in aged populations. However, the major causes of the age-dependent decline of islet function are still disputed. Here we demonstrate that aging of pancreatic islets in mice and humans is notably associated with inflammation and fibrosis of islet blood vessels but does not affect glucose sensing and the insulin secretory capacity of islet beta cells. Accordingly, when transplanted into the anterior chamber of the eye of young mice with diabetes, islets from old mice are revascularized with healthy blood vessels, show strong islet cell proliferation, and fully restore control of glycemia. Our results indicate that beta cell function does not decline with age and suggest that islet function is threatened by an age-dependent impairment of islet vascular function. Strategies to mitigate age-dependent dysregulation in glycemia should therefore target systemic and/or local inflammation and fibrosis of the aged islet vasculature.

Principal Component Structuring of the Non-REM Sleep EEG Spectrum in Older Adults Yields Age-Related Changes in the Sleep and Wake Drives

Age-related disturbances of the sleep-wake cycle can reflect ontogenetic changes in regulatory mechanisms underlying normal and pathological aging, but the exact nature of these changes remains unclear. The present report is the first attempt to apply principal component analysis to the electroencephalographic (EEG) spectrum to examine of whether the observed age-related changes in the objective sleep measures can be linked to the opponent sleep-promoting and wake-promoting processes. The EEG indicators of these processes--scores on the 1st and 2nd principal components of the EEG spectrum, respectively--were compared in 15 older (57-74 years) and 16 younger (20-31 years) healthy volunteers. The scores were calculated for non-REM sleep episodes which occurred during ten 75-min naps scheduled every 150 min throughout a 40-h constant routine protocol. Both, a decrease of the 1st principal component score and an increase of the 2nd principal component score were found to contribute to such most obvious age-related modification of the sleep EEG spectrum as attenuation of EEG slow-wave activity in older people. Therefore, we concluded that the normal aging process can reflect both a weakening of the sleep-promoting process and a strengthening of the wake-promoting process, respectively. Such bidirectional changes in chronoregulatory processes may explain why sleep of older people is characterized by the few profitable and a number of detrimental features (i.e., a better ability to cope with daytime sleepiness and sleep loss vs. difficulty of falling asleep, decreased total nighttime sleep, "lightened" and fragmentized sleep, unwanted early morning awakenings, etc.).

Exposure to light at night accelerates aging and spontaneous uterine carcinogenesis in female 129/Sv mice

The effect of the constant illumination on the development of spontaneous tumors in female 129/Sv mice was investigated. Forty-six female 129/Sv mice starting from the age of 2 mo were kept under standard light/dark regimen [12 h light (70 lx):12hr dark; LD, control group], and 46 of 129/Sv mice were kept under constant illumination (24 h a day, 2,500 lx, LL) from the age of 5 mo until to natural death. The exposure to the LL regimen significantly accelerated body weight gain, increased body temperature as well as acceleration of age-related disturbances in estrous function, followed by significant acceleration of the development of the spontaneous uterine tumors in female 129/Sv mice. Total tumor incidence as well as a total number of total or malignant tumors was similar in LL and LD group (p > 0.05). The mice from the LL groups survived less than those from the LD group (χ2 = 8.5; p = 0.00351, log-rank test). According to the estimated parameters of the Cox’s regression model, constant light regimen increased the relative risk of death in female mice compared with the control (LD) group (p = 0.0041). The data demonstrate in the first time that the exposure to constant illumination was followed by the acceleration of aging and spontaneous uterine tumorigenesis in female 129/Sv mice.

Age-dependent changes in gastrointestinal motility

The mechanisms of the motor function are studied for more than 100 years, howe­ver, they have not been established completely. Understanding those mechanisms is of great importance since the disturbances of gastrointestinal motility underlay in pathogeneses of many diseases, such as colitis, constipations, irritable bowel syndrome and others. This review is devoted to analysis of literature data of the age-related changes in the motility function of digestive tract. We have searched articles on a particular issue and have analyzed them in accordance with the parts of the digestive tract. Main attention has been paid to age-dependent functional and regulatory changes in the digestive tract. The mechanisms underlying in pathogenesis of age-related diseases of motor function of the digestive tract have not been deeply studied. Without the establishment of these mechanisms, it is impossible to create new drugs for prophylaxis and treatment of age-related disturbances in motor function of the gastrointestinal (GI) motility. Keywords: gastrointestinal motility, age.

Peculiarities of brain mechanisms of regulation of level of wakefulness and of cognitive activity in children with retardation of psychic development and in healthy children of the same age

The work opens possibilities of the of modifications of the developed at the Laboratory systemic-integrative psychophysiological approach to study of the age-related organization or of deviation from norm in formation of superslow informational-controlling brain systems participating in mechanisms of regulation of the wakefulness level and of cognitive activity in the 5-7-year old healthy children and in children of the same age group with retardation of psychic and speech development of the cerebral-organic genesis. There are disclosed peculiarities of organization of: (a) cortical-brainstem and limbic-reticular mechanisms of regulation of the level of wakefulness; (b) suprasegmentary mechanisms of autonomic, hemodynamic, and oxygen-dependent energy supply of the wakefulness level in the examined children's contingent. There are substantiated concepts about interrelations of peculiarities of the level of actual development of emotional and cognitive spheres with age-related peculiarities or disturbances of formation of mechanisms of regulation of the wakefulness level, its autonomic and hemodynamic provision as well as of the oxygen-dependent energetic potential.

Effect of mitochondria-targeted antioxidant SkQ1 on aging, lifespan, and spontaneous carcinogenesis in three strains of mice

Female mice of the outbred SHR strain, the inbred 129/Sv strain, and the high cancer rate transgenic HER-2/neu strain were given a mitochondria-targeted derivative of plastoquinone SkQ1 (10E (6′-plastoquinonyl)-decyltriphenylphosphonium) in drinking water from the age of two months at doses of 0.5–2500 nmol/kg of body weight per day. The animals of the control groups received drinking water without the drug. We evaluated the age-related changes in the body weight and temperature, the amount of consumed drinking water and food, estrous function, locomotor activity in the “open field” test, muscle strength and fatigability in the wire suspension test, and anxiety in the elevated plus maze, as well as indices of lifespan and carcinogenesis. We did not observe substantial differences in the body weight, temperature, and amount of consumed drinking water and food between the animals of the experimental and control groups. In SHR mice treated with SkQ1, we observed a tendency toward the inhibition of age-related disturbances of the estrous function. The drug did not influence estrous function in the transgenic or inbred animals. SkQ1 substantially decreased locomotor activity and exercise tolerance in 129/Sv and SHR mice and did not affect anxiety in SHR mice. We observed a tendency toward the inhibition of external indices of aging in SHR mice treated with various doses of SkQ1. In SHR mice, administration of SkQ1 at doses of 0.5–50 nmol/kg was associated with an elevation of the main parameters of the lifespan (LS), including the mean LS value, the mean LS value of the last 10%, the median value, and the maximum LS value. It did not influence the LS parameters in the female 129/Sv and HER-2/neu mice. In three mice strains studied, SkQ1 treatment at all doses did not substantially affect spontaneous carcinogenesis; however, it significantly decreased mortality in SHR mice from nontumor-related pathologies. Our data support the hypothesis on the geroprotective properties of SkQ1 and a lack of general toxic and carcinogenic activity after long-term treatment with it.

Neurogenesis in the enteric nervous system.

The enteric nervous system (ENS) represents the highly organized intrinsic innervation of the gastrointestinal tract and plays a critical role for all stages of postnatal life. Severe disturbances of ENS function can significantly influence life quality or, in severe cases, can have acute life-threatening effects. Recent in vitro and in vivo studies demonstrated the persistence of neural stem cells in postnatal gut and there seem to be many interesting parallels to the more extensively studied neural stem cells in the brain. Enteric stem cells have been proposed as an appropriate cell source to provide an alternative therapeutic option for a number of neurogastrointestinal diseases, however a better understanding of these cells would be crucial for the translation of cell-based therapies into clinic. This review tries to highlight the recent findings in the field of enteric neurogenesis and additionally gives a brief overview about the development, structure and function of the ENS and about the developmental or age-related disturbances affecting the ENS.