Nutrition Interventions of Herbal Compounds on Cellular Senescence.

When cells undergo large-scale senescence, organ aging ensues, resulting in irreversible organ pathology and organismal aging. The study of senescence in cells provides an important avenue to understand the factors that influence aging and can be used as one of the useful tools for examining age-related human diseases. At present, many herbal compounds have shown effects on delaying cell senescence. This review summarizes the main characteristics and mechanisms of cell senescence, age-related diseases, and the recent progress on the natural products targeting cellular senescence, with the aim of providing insights to aid the clinical management of age-related diseases.

Brain and testicular metabonomics revealed the protective effects of Guilingji on senile sexual dysfunction rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Guilingji (GLJ), which has been used to treat male diseases in China for centuries, contains 28 Chinese herbs and was previously established as an effective treatment for male sexual dysfunction. However, its mechanism of action remains unclear. AIM OF THE STUDY: To explore the efficacy and mechanism of action of GLJ in improving senile sexual dysfunction (SSD) in aging rats. MATERIALS AND METHODS: An aging rat model of SSD was induced by the subcutaneous injection of d-galactose (300 mg⋅kg-1) and used to analyse the effects of GLJ (different concentrations of 37.5, 75, and 150 mg⋅kg-1) on the mating of aging rats. At the end of the 8th week, histopathological analysis of testicular tissues, assessment of the hypothalamic-pituitary-gonadal (HPG) axis hormone levels in serum or brain, and metabonomics analysis of the brain and testicular tissue with liquid chromatography-mass spectrometry was performed to explore the mechanism of action of GLJ. RESULT: After treatment with GLJ, the mount and ejaculation latency levels were increased in the treatment group than those in model group (P < 0.05), moreover, the testicular morphology was improved. Gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) levels in rats were also improved significant (P < 0.05) compared with those in the model group. Furthermore, the metabonomics results in the testicular and brain tissue showed that GLJ improved SSD by adjusting amino acid and lipid metabolism. CONCLUSION: This study integrated the complementary metabolic profiles of the target tissues. GLJ might affect SSD rats by regulating amino acid and lipid metabolism and may modulate sensitivity to the signaling pathway in the HPG axis. This study provides an essential basis for the broad clinical application of GLJ.

Kampo formulas alleviate aging-related emotional disturbances and neuroinflammation in male senescence-accelerated mouse prone 8 mice.

Aging-induced neuroinflammation, also known as neuroinflammaging, plays a pivotal role in emotional disturbances, including depression and anxiety, in older individuals, thereby leading to cognitive dysfunction. Although numerous studies have focused on therapeutic strategies for cognitive impairment in older individuals, little research has been performed on treating its preceding emotional disturbances. Here, we examined whether Kampo formulas (kososan [KS], nobiletin-rich kososan [NKS], and hachimijiogan [HJG]) can ameliorate aging-induced emotional disturbances and neuroinflammation in mice. The depression-like behaviors observed in SAMP8 mice, relative to normally aging SAMR1 mice, were significantly prevented by treatment with Kampo formulas for 13 weeks. Western blot analysis revealed that hippocampal neuroinflammation was significantly abrogated by Kampo formulas. KS and NKS also significantly attenuated the hippocampal neuroinflammatory priming induced by lipopolysaccharide (LPS, 0.33 mg/kg, i.p.) challenge in SAMP8 mice. Hippocampal IL-1ß, IL-6, and MCP-1 levels were significantly decreased in NKS-treated SAMP8 mice. KS and NKS showed significantly reduced tau accumulation in the brains of SAMP8 mice. RNA-sequencing revealed that each Kampo formula led to unique dynamics of hippocampal gene expression and appeared to abrogate hippocampal inflammatory responses. HJG significantly blocked the LPS-induced increase in serum IL-6 and MCP-1. These results suggest that Kampo formulas would be useful for treating aging-induced depression, in part by regulating neuroinflammatory pathways. This finding may pave the way for the development of therapeutic strategies for aging-related emotional disturbances, which may contribute to the prevention of cognitive dysfunction in older individuals.

Age-related alterations to working memory and to pyramidal neurons in the prefrontal cortex of rhesus monkeys begin in early middle-age and are partially ameliorated by dietary curcumin.

Layer 3 (L3) pyramidal neurons in aged rhesus monkey lateral prefrontal cortex (LPFC) exhibit significantly elevated excitability in vitro and reduced spine density compared to neurons in young subjects. The time-course of these alterations, and whether they can be ameliorated in middle age by the powerful anti-oxidant curcumin is unknown. We compared the properties of L3 pyramidal neurons from the LPFC of behaviorally characterized rhesus monkeys over the adult lifespan using whole-cell patch clamp recordings and neuronal reconstructions. Working memory (WM) impairment, neuronal hyperexcitability, and spine loss began in middle age. There was no significant relationship between neuronal properties and WM performance. Middle-aged subjects given curcumin exhibited better WM performance and less neuronal excitability compared to control subjects. These findings suggest that the appropriate time frame for intervention for age-related cognitive changes is early middle age, and points to the efficacy of curcumin in delaying WM decline. Because there was no relationship between excitability and behavior, the effects of curcumin on these measures appear to be independent.

A neural signature of regularity in sound is reduced in older adults.

Sensitivity to repetitions in sound amplitude and frequency is crucial for sound perception. As with other aspects of sound processing, sensitivity to such patterns may change with age, and may help explain some age-related changes in hearing such as segregating speech from background sound. We recorded magnetoencephalography to characterize differences in the processing of sound patterns between younger and older adults. We presented tone sequences that either contained a pattern (made of a repeated set of tones) or did not contain a pattern. We show that auditory cortex in older, compared to younger, adults is hyperresponsive to sound onsets, but that sustained neural activity in auditory cortex, indexing the processing of a sound pattern, is reduced. Hence, the sensitivity of neural populations in auditory cortex fundamentally differs between younger and older individuals, overresponding to sound onsets, while underresponding to patterns in sounds. This may help to explain some age-related changes in hearing such as increased sensitivity to distracting sounds and difficulties tracking speech in the presence of other sound.

Hypothalamic inflammation in metabolic disorders and aging.

The hypothalamus is a critical brain region for the regulation of energy homeostasis. Over the years, studies on energy metabolism primarily focused on the neuronal component of the hypothalamus. Studies have recently uncovered the vital role of glial cells as an additional player in energy balance regulation. However, their inflammatory activation under metabolic stress condition contributes to various metabolic diseases. The recruitment of monocytes and macrophages in the hypothalamus helps sustain such inflammation and worsens the disease state. Neurons were found to actively participate in hypothalamic inflammatory response by transmitting signals to the surrounding non-neuronal cells. This activation of different cell types in the hypothalamus leads to chronic, low-grade inflammation, impairing energy balance and contributing to defective feeding habits, thermogenesis, and insulin and leptin signaling, eventually leading to metabolic disorders (i.e., diabetes, obesity, and hypertension). The hypothalamus is also responsible for the causation of systemic aging under metabolic stress. A better understanding of the multiple factors contributing to hypothalamic inflammation, the role of the different hypothalamic cells, and their crosstalks may help identify new therapeutic targets. In this review, we focus on the role of glial cells in establishing a cause-effect relationship between hypothalamic inflammation and the development of metabolic diseases. We also cover the role of other cell types and discuss the possibilities and challenges of targeting hypothalamic inflammation as a valid therapeutic approach.

Assessing Creatine Supplementation for Neuroprotection against Perinatal Hypoxic-Ischaemic Encephalopathy: A Systematic Review of Perinatal and Adult Pre-Clinical Studies.

There is an important unmet need to develop interventions that improve outcomes of hypoxic-ischaemic encephalopathy (HIE). Creatine has emerged as a promising neuroprotective agent. Our objective was to systematically evaluate the preclinical animal studies that used creatine for perinatal neuroprotection, and to identify knowledge gaps that need to be addressed before creatine can be considered for pragmatic clinical trials for HIE. METHODS: We reviewed preclinical studies up to 20 September 2021 using PubMed, EMBASE and OVID MEDLINE databases. The SYRCLE risk of bias assessment tool was utilized. RESULTS: Seventeen studies were identified. Dietary creatine was the most common administration route. Cerebral creatine loading was age-dependent with near term/term-equivalent studies reporting higher increases in creatine/phosphocreatine compared to adolescent-adult equivalent studies. Most studies did not control for sex, study long-term histological and functional outcomes, or test creatine post-HI. None of the perinatal studies that suggested benefit directly controlled core body temperature (a known confounder) and many did not clearly state controlling for potential study bias. CONCLUSION: Creatine is a promising neuroprotective intervention for HIE. However, this systematic review reveals key knowledge gaps and improvements to preclinical studies that must be addressed before creatine can be trailed for neuroprotection of the human fetus/neonate.

Impact of Selenium on Biomarkers and Clinical Aspects Related to Ageing. A Review.

Selenium (Se) is an essential dietary trace element that plays an important role in the prevention of inflammation, cardiovascular diseases, infections, and cancer. Selenoproteins contain selenocysteine in the active center and include, i.a., the enzymes thioredoxin reductases (TXNRD1-3), glutathione peroxidases (GPX1-4 and GPX6) and methionine sulfoxide reductase, involved in immune functions, metabolic homeostasis, and antioxidant defense. Ageing is an inevitable process, which, i.a., involves an imbalance between antioxidative defense and reactive oxygen species (ROS), changes in protein and mitochondrial renewal, telomere attrition, cellular senescence, epigenetic alterations, and stem cell exhaustion. These conditions are associated with mild to moderate inflammation, which always accompanies the process of ageing and age-related diseases. In older individuals, Se, by being a component in protective enzymes, operates by decreasing ROS-mediated inflammation, removing misfolded proteins, decreasing DNA damage, and promoting telomere length. Se-dependent GPX1-4 and TXNRD1-3 directly suppress oxidative stress. Selenoprotein H in the cell nucleus protects DNA, and selenoproteins residing in the endoplasmic reticulum (ER) assist in the removal of misfolded proteins and protection against ER stress. In this review, we highlight the role of adequate Se status for human ageing and prevention of age-related diseases, and further its proposed role in preservation of telomere length in middle-aged and elderly individuals.

Reversal of brain aging by targeting telomerase: A nutraceutical approach.

Telomeres, the protective caps of chromosomes, shorten with age, as telomerase, the enzyme responsible for the compensation of telomere erosion, is inactive in the majority of cells. Telomere shortening and subsequent cell senescence lead to tissue aging and age­related diseases. Neurodegenerative disorders, characterized by the progressive loss of neurons among other hallmarks of aged tissue, and poor cognitive function, have been associated with a short telomere length. Thus, telomerase activity has emerged as a therapeutic target, with novel agents being under investigation. The present study aimed to examine the effects of a novel natural telomerase activator, 'Reverse™', containing Centella asiatica extract, vitamin C, zinc and vitamin D3 on the brains of 18­month­old rats. The administration of the 'Reverse™' supplement for 3 months restored telomerase reverse transcriptase (TERT) expression in the brains of rats, as revealed by ELISA and immunohistochemistry. In addition, the findings from PCR­ELISA demonstrated an enhanced telomerase activity in the cerebellum and cortex cells in the brains of rats treated with the 'Reverse™' supplement. The histopathological findings confirmed a structural reversibility effect close to the differentiation observed in the young control group of rats treated with two capsules/kg body weight of the 'Reverse™' supplement. On the whole, the findings of the present study provide a strong indication that an increased telomerase activity and TERT expression may be achieved not only in the postnatal or embryonic period, but also in the brains of middle­aged rats through nutraceutical supplementation. The use of the 'Reverse™' supplement may thus contribute to the potential alleviation of a number of central nervous system diseases.

Klotho and calciprotein particles as therapeutic targets against accelerated ageing.

The klotho gene, named after a Greek goddess who spins the thread of life, was identified as a putative 'ageing-suppressor' gene. Klotho-deficient mice exhibit complex ageing-like phenotypes including hypogonadism, arteriosclerosis (vascular calcification), cardiac hypertrophy, osteopenia, sarcopenia, frailty, and premature death. Klotho protein functions as the obligate co-receptor for fibroblast growth factor-23 (FGF23), a bone-derived hormone that promotes urinary phosphate excretion in response to phosphate intake. Thus, Klotho-deficient mice suffer not only from accelerated ageing but also from phosphate retention due to impaired phosphate excretion. Importantly, restoration of the phosphate balance by placing Klotho-deficient mice on low phosphate diet rescued them from premature ageing, leading us to the notion that phosphate accelerates ageing. Because the extracellular fluid is super-saturated in terms of phosphate and calcium ions, an increase in the phosphate concentration can trigger precipitation of calcium-phosphate. In the blood, calcium-phosphate precipitated upon increase in the blood phosphate concentration is adsorbed by serum protein fetuin-A to form colloidal nanoparticles called calciprotein particles (CPPs). In the urine, CPPs appear in the renal tubular fluid when FGF23 increases phosphate load excreted per nephron. CPPs can induce cell damage, ectopic calcification, and inflammatory responses. CPPs in the blood can induce arteriosclerosis and non-infectious chronic inflammation, whereas CPPs in the urine can induce renal tubular damage and interstitial inflammation/fibrosis. Thus, we propose that CPPs behave like a pathogen that accelerates ageing and should be regarded as a novel therapeutic target against age-related disorders including chronic kidney disease.

The Glyoxalase System in Age-Related Diseases: Nutritional Intervention as Anti-Ageing Strategy.

The glyoxalase system is critical for the detoxification of advanced glycation end-products (AGEs). AGEs are toxic compounds resulting from the non-enzymatic modification of biomolecules by sugars or their metabolites through a process called glycation. AGEs have adverse effects on many tissues, playing a pathogenic role in the progression of molecular and cellular aging. Due to the age-related decline in different anti-AGE mechanisms, including detoxifying mechanisms and proteolytic capacities, glycated biomolecules are accumulated during normal aging in our body in a tissue-dependent manner. Viewed in this way, anti-AGE detoxifying systems are proposed as therapeutic targets to fight pathological dysfunction associated with AGE accumulation and cytotoxicity. Here, we summarize the current state of knowledge related to the protective mechanisms against glycative stress, with a special emphasis on the glyoxalase system as the primary mechanism for detoxifying the reactive intermediates of glycation. This review focuses on glyoxalase 1 (GLO1), the first enzyme of the glyoxalase system, and the rate-limiting enzyme of this catalytic process. Although GLO1 is ubiquitously expressed, protein levels and activities are regulated in a tissue-dependent manner. We provide a comparative analysis of GLO1 protein in different tissues. Our findings indicate a role for the glyoxalase system in homeostasis in the eye retina, a highly oxygenated tissue with rapid protein turnover. We also describe modulation of the glyoxalase system as a therapeutic target to delay the development of age-related diseases and summarize the literature that describes the current knowledge about nutritional compounds with properties to modulate the glyoxalase system.

Improper Remodeling of Organelles Deputed to Ca2+ Handling and Aerobic ATP Production Underlies Muscle Dysfunction in Ageing.

Proper skeletal muscle function is controlled by intracellular Ca2+ concentration and by efficient production of energy (ATP), which, in turn, depend on: (a) the release and re-uptake of Ca2+ from sarcoplasmic-reticulum (SR) during excitation-contraction (EC) coupling, which controls the contraction and relaxation of sarcomeres; (b) the uptake of Ca2+ into the mitochondrial matrix, which stimulates aerobic ATP production; and finally (c) the entry of Ca2+ from the extracellular space via store-operated Ca2+ entry (SOCE), a mechanism that is important to limit/delay muscle fatigue. Abnormalities in Ca2+ handling underlie many physio-pathological conditions, including dysfunction in ageing. The specific focus of this review is to discuss the importance of the proper architecture of organelles and membrane systems involved in the mechanisms introduced above for the correct skeletal muscle function. We reviewed the existing literature about EC coupling, mitochondrial Ca2+ uptake, SOCE and about the structural membranes and organelles deputed to those functions and finally, we summarized the data collected in different, but complementary, projects studying changes caused by denervation and ageing to the structure and positioning of those organelles: a. denervation of muscle fibers-an event that contributes, to some degree, to muscle loss in ageing (known as sarcopenia)-causes misplacement and damage: (i) of membrane structures involved in EC coupling (calcium release units, CRUs) and (ii) of the mitochondrial network; b. sedentary ageing causes partial disarray/damage of CRUs and of calcium entry units (CEUs, structures involved in SOCE) and loss/misplacement of mitochondria; c. functional electrical stimulation (FES) and regular exercise promote the rescue/maintenance of the proper architecture of CRUs, CEUs, and of mitochondria in both denervation and ageing. All these structural changes were accompanied by related functional changes, i.e., loss/decay in function caused by denervation and ageing, and improved function following FES or exercise. These data suggest that the integrity and proper disposition of intracellular organelles deputed to Ca2+ handling and aerobic generation of ATP is challenged by inactivity (or reduced activity); modifications in the architecture of these intracellular membrane systems may contribute to muscle dysfunction in ageing and sarcopenia.

Fatty acids and beyond: Age and Alzheimer's disease related changes in lipids reveal the neuro-nutraceutical potential of lipids in cognition.

Lipids are essential in maintaining brain function, and lipid profiles have been reported to be altered in aged and Alzheimer's disease (AD) brains as compared to healthy mature brains. Both age and AD share common metabolic hallmarks such as increased oxidative stress and perturbed metabolic function, and age remains the most strongly correlated risk factor for AD, a neurodegenerative disease. A major accompanying pathological symptom of these conditions is cognitive impairment, which is linked with changes in lipid metabolism. Thus, nutraceuticals that affect brain lipid metabolism or lipid levels as a whole have the potential to ameliorate cognitive decline. Lipid analyses and lipidomic studies reveal changes in specific lipid types with aging and AD, which can identify potential lipid-based nutraceuticals to restore the brain to a healthy lipid phenotype. The brain lipid profile can be influenced directly with dietary administration of lipids themselves, although because of synergistic effects of nutrients it may be more useful to consider a multi-component diet rather than single nutrient supplementation. Gut microbiota also serve as a source of beneficial lipids, and the value of treatments that manipulate the composition of gut microbiome should not be ignored. Lastly, instead of direct supplementation, compounds that affect pathways involved with lipid metabolism should also be considered as a way of manipulating lipid levels to improve cognition. In this review, we briefly discuss the role of lipids in the brain, the changing lipid profile in AD, current research on lipid-based nutraceuticals and their therapeutic potential to combat cognitive impairment.

Betaine Delayed Muscle Loss by Attenuating Samtor Complex Inhibition for mTORC1 Signaling Via Increasing SAM Level.

SCOPE: The muscle loss during aging results from the blunt of protein synthesis and poses threat to the elderly health. This study aims to investigate whether betaine affects muscle loss by improving protein synthesis. METHODS AND RESULTS: Male C57BL/6J mice are raised from age 12 or 15 months. Mice are fed with AIN-93M diet without or with 2% w/v betaine in distilled water as control group or betaine intervention group (Bet), respectively. Betaine supplementation to mice demonstrates better body composition, grip strength, and motor function. Muscle morphology upregulates expression of myogenic regulate factors, and elevates myosin heavy chain and also improves in Bet group. Betaine promotes muscle protein synthesis via tethering mammalian target of rapamycin complex1 protein kinase (mTORC1) on the lysosomal membrane thereby activating mTORC1 signaling. All these effects aforementioned are time-dependent (p < 0.05). Ultrahigh-performance liquid chromatography results show that betaine increases S-adenosyl-l-methionine (SAM) via methionine cycle. SAM sensor-Samtor-overexpression in C2C12 cells could displace mTORC1 from lysosome thereby inhibiting the mTORC1 signaling. Addition of betaine attenuates this inhibition by increasing SAM level and then disrupting interaction of Samtor complex. CONCLUSIONS: These observations indicate that betaine could promisingly promote protein synthesis to delay age-related muscle loss.

Determining the effect of aging, recovery time, and post-stroke memantine treatment on delayed thalamic gliosis after cortical infarct.

Secondary injury following cortical stroke includes delayed gliosis and eventual neuronal loss in the thalamus. However, the effects of aging and the potential to ameliorate this gliosis with NMDA receptor (NMDAR) antagonism are not established. We used the permanent distal middle cerebral artery stroke model (pdMCAO) to examine secondary thalamic injury in young and aged mice. At 3 days post-stroke (PSD3), slight microgliosis (IBA-1) and astrogliosis (GFAP) was evident in thalamus, but no infarct. Gliosis increased dramatically through PSD14, at which point degenerating neurons were detected. Flow cytometry demonstrated a significant increase in CD11b+/CD45int microglia (MG) in the ipsilateral thalamus at PSD14. CCR2-RFP reporter mouse further demonstrated that influx of peripheral monocytes contributed to the MG/Mϕ population. Aged mice demonstrated reduced microgliosis and astrogliosis compared with young mice. Interestingly, astrogliosis demonstrated glial scar-like characteristics at two years post-stroke, but not by 6 weeks. Lastly, treatment with memantine (NMDAR antagonist) at 4 and 24 h after stroke significantly reduced gliosis at PSD14. These findings expand our understanding of gliosis in the thalamus following cortical stroke and demonstrate age-dependency of this secondary injury. Additionally, these findings indicate that delayed treatment with memantine (an FDA approved drug) provides significant reduction in thalamic gliosis.

Endogenous FGF-2 levels impact FGF-2/BMP-2 growth factor delivery dosing in aged murine calvarial bone defects.

Bone repair in elderly mice has been shown to be improved or negatively impacted by supplementing the highly osteogenic bone morphogenetic protein-2 (BMP-2) with fibroblast growth factor-2 (FGF-2). To better predict the outcome of FGF-2 supplementation, we investigated whether endogenous levels of FGF-2 play a role in optimal dosing of FGF-2 for augmenting BMP-2 activity in elderly mice. In vivo calvarial bone defect studies in Fgf2 knockout mice with wildtype controls were conducted with the growth factors delivered in a highly localized manner from a biomimetic calcium phosphate/polyelectrolyte multilayer coating applied to a bone graft substitute. Endogenous FGF-2 levels were measured in old mice versus young and found to decrease with age. Optimal dosing for improving bone defect repair correlated with levels of endogenous FGF-2, with a larger dose of FGF-2 required to have a positive effect on bone healing in the Fgf2 knockout mice. The same dose in wildtype old mice, with higher levels of FGF-2, promoted chondrogenesis and increased osteoclast activity. The results suggest a personalized medicine approach, based on a knowledge of endogenous levels of FGF-2, should guide FGF-2 supplementation in order to avoid provoking excessive bone resorption and cartilage formation, both of which inhibited calvarial bone repair.

Inferior collicular cells that project to the auditory thalamus are increasingly surrounded by perineuronal nets with age.

The age-related loss of GABA in the inferior colliculus (IC) likely plays a role in the development of age-related hearing loss. Perineuronal nets (PNs), specialized aggregates of extracellular matrix, increase with age in the IC. PNs, associated with GABAergic neurotransmission, can stabilize synapses and inhibit structural plasticity. We sought to determine whether PN expression increased on GABAergic and non-GABAergic IC cells that project to the medial geniculate body (MG). We used retrograde tract-tracing in combination with immunohistochemistry for glutamic acid decarboxylase and Wisteria floribunda agglutinin across three age groups of Fischer Brown Norway rats. Results demonstrate that PNs increase with age on lemniscal and non-lemniscal IC-MG cells, however two key differences exist. First, PNs increased on non-lemniscal IC-MG cells during middle-age, but not until old age on lemniscal IC-MG cells. Second, increases of PNs on lemniscal IC-MG cells occurred on non-GABAergic cells rather than on GABAergic cells. These results suggest that synaptic stabilization and reduced plasticity likely occur at different ages on a subset of the IC-MG pathway.

Therapeutic Efficacy of Aerobic Exercise Training along with Oak Husk Hydroalcoholic Extract for Amelioration of Inflammation in Obese Elderly Male Mice.

BACKGROUND: Fibrinogen and interleukin-1ß as a proinflammatory cytokine and interleukin-10 and nesfatin-1 as an anti-inflammatory cytokine have an important role in the development and prevention of systemic inflammation and incidence of obesity-induced diseases. Thus, this study is aimed at the interaction effects of aerobic training and oak husk hydroalcoholic extract consumption on plasma levels of fibrinogen, interleukin-1ß, nesfatin-1, and interleukin-10 in obese elderly male mice. MATERIALS AND METHODS: In this experimental study, 40 fat male mice were fed a high-fat diet for 4 weeks to induce obesity, and subsequently, they were divided randomly into four groups: control, supplement, exercise-placebo, and exercise-supplement. The training groups performed aerobic exercise 5 days a week for 6 weeks (approximately 80-75% VOmax 2). The supplement groups received a solution of oak husk hydroalcoholic extract at a dose of 20 milligram per kilogram of body weight for 6 weeks. Blood samples were taken 48 h after the last training session, and the levels of IL-10, fibrinogen, IL-1ß, and nesfatin-1 were measured. Data were analyzed using one-way ANOVA and LSD post hoc tests. RESULTS: The results showed that six-week training and oak husk hydroalcoholic extract consumption significantly increased the levels of IL-10 and nesfatin-1 in experimental groups (P < 0.001). Also, the levels of fibrinogen and IL-1ß decreased significantly in training groups. Averages between group variations of all indicators were statistically significant, and they were more meaningfully pronounced in the exercise-supplement group than other groups (P ≤ 0.05). CONCLUSIONS: Considering the results of the present study, the use of moderate aerobic exercise and oak husk hydroalcoholic extract is recommended to reduce the risk of obesity; it may also have a positive effect on inflammatory factors.

Changes in brown adipose tissue lipid mediator signatures with aging, obesity, and DHA supplementation in female mice.

Brown adipose tissue (BAT) dysfunction in aging and obesity has been related to chronic unresolved inflammation, which could be mediated by an impaired production of specialized proresolving lipid mediators (SPMs), such as Lipoxins-LXs, Resolvins-Rvs, Protectins-PDs, and Maresins-MaRs. Our aim was to characterize the changes in BAT SPMs signatures and their association with BAT dysfunction during aging, especially under obesogenic conditions, and their modulation by a docosahexaenoic acid (DHA)-rich diet. Lipidomic, functional, and molecular studies were performed in BAT of 2- and 18-month-old lean (CT) female mice and in 18-month-old diet-induced obese (DIO) mice fed with a high-fat diet (HFD), or a DHA-enriched HFD. Aging downregulated Prdm16 and UCP1 levels, especially in DIO mice, while DHA partially restored them. Arachidonic acid (AA)-derived LXs and DHA-derived MaRs and PDs were the most abundant SPMs in BAT of young CT mice. Interestingly, the sum of LXs and of PDs were significantly lower in aged DIO mice compared to young CT mice. Some of the SPMs most significantly reduced in obese-aged mice included LXB4 , MaR2, 4S,14S-diHDHA, 10S,17S-diHDHA (a.k.a. PDX), and RvD6. In contrast, DHA increased DHA-derived SPMs, without modifying LXs. However, MicroPET studies showed that DHA was not able to counteract the impaired cold exposure response in BAT of obese-aged mice. Our data suggest that a defective SPMs production could underlie the decrease of BAT activity observed in obese-aged mice, and highlight the relevance to further characterize the physiological role and therapeutic potential of specific SPMs on BAT development and function.

Causal structural covariance network revealing atrophy progression in Alzheimer's disease continuum.

The structural covariance network (SCN) has provided a perspective on the large-scale brain organization impairment in the Alzheimer's Disease (AD) continuum. However, the successive structural impairment across brain regions, which may underlie the disrupted SCN in the AD continuum, is not well understood. In the current study, we enrolled 446 subjects with AD, mild cognitive impairment (MCI) or normal aging (NA) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The SCN as well as a casual SCN (CaSCN) based on Granger causality analysis were applied to the T1-weighted structural magnetic resonance images of the subjects. Compared with that of the NAs, the SCN was disrupted in the MCI and AD subjects, with the hippocampus and left middle temporal lobe being the most impaired nodes, which is in line with previous studies. In contrast, according to the 194 subjects with records on CSF amyloid and Tau, the CaSCN revealed that during AD progression, the CaSCN was enhanced. Specifically, the hippocampus, thalamus, and precuneus/posterior cingulate cortex (PCC) were identified as the core regions in which atrophy originated and could predict atrophy in other brain regions. Taken together, these findings provide a comprehensive view of brain atrophy in the AD continuum and the relationships among the brain atrophy in different regions, which may provide novel insight into the progression of AD.