Oroxylin A ameliorates ultraviolet radiation-induced premature skin aging by regulating oxidative stress via the Sirt1 pathway.

Skin is susceptible to premature aging in response to ultraviolet (UV) radiation-induced oxidative stress, which can ultimately result in aberrant aging or age-related disorders. Accordingly, strategies that can be adopted to mitigate oxidative stress may contribute to protecting skin from induced aging-related damage, thereby offering promising approaches for the treatment of skin diseases and disorders. In this regard, oroxylin A (OA), a natural flavonoid isolated from certain plants used in traditional Chinese medicine, is considered to have notable antioxidant, anti-inflammatory, and anti-apoptotic properties, and is often used to treat certain inflammatory diseases. To date, however, there has been comparatively little research on the effects of OA with respect skin aging. In this study, we utilized UV radiation-induced mouse and cellular models of aging to assess the efficacy of OA in protecting against skin aging. Subsequently, to elucidate the potential mechanisms underlying the protective effect of OA on skin aging, we performed molecular docking analysis to investigate the involvement of the anti-aging gene Sirt1, which was further confirmed on the basis of Sirt1 gene silencing. We accordingly demonstrated that by promoting an increase in the expression of Sirt1, OA can contribute to suppressing UV-induced skin photo-aging in cells/mice by reducing oxidative stress. Furthermore, we established that by activating Sirt1, OA can also promote the dissociation of Nrf2 from Keap1 and its subsequent nuclear translocation. Collectively, our findings in this study reveal OA to be an effective natural compound that can be administered to delay the aging of skin triggered by UV, both in vivo and in vitro, by binding to Sirt1 to promote the deacetylation and nuclear translocation of Nrf2, thereby contributing to a reduction in oxidative stress. These findings may this provide a therapeutic target for the prevention of skin aging or aging-induced skin diseases.

Optimization of parameters for obtaining callus, suspension, and root cultures of meadowsweet (filipendula ulmaria) to isolate the largest number of biologically active substances with geroprotective properties / Otimização de parâmetros para obtenção de culturas de calos, suspensão e raiz de Ulmária (Filipendula ulmaria) para isolar o maior número de substâncias biologicamente ativas com propriedades geroprotetoras

The study of biologically active substances-secondary metabolites of plants that exhibit geroprotective properties is an actual and popular direction in medicine to prevent early aging. This work aims to select the cultivation parameters for obtaining in vitro cell cultures of meadowsweet containing the largest amount of biologically active substances (BAS) for their further extraction as candidate substances for geroprotectors. To specify the effectiveness of the selected cell culture cultivation parameters, biomass growth for callus and root cultures, growth index, specific growth rate, and viability for suspension cultures was carried out. The study results made it possible to select the nutrient media for the cultivation of cell cultures of meadowsweet. It has been found that the greater the antioxidant activity of the extracts, the greater the antimicrobial properties it exhibits. In this study, cell cultures in vitro and alcohol extracts from the plant Filipendula ulmaria were considered as raw materials rich in candidate substances for geroprotectors. According to the data obtained, the plant is rich in hydroxybenzoic and salicylic acids, spireoside, avicularin, and hyperoside.

O estudo de substâncias biologicamente ativas - metabólitos secundários de plantas que apresentam propriedades geroprotetoras - é uma tendência atual e popular no campo da medicina para a prevenção do envelhecimento precoce. O objetivo deste trabalho foi selecionar os parâmetros de cultivo para obtenção de culturas celulares in vitro de Ulmária contendo a maior quantidade de substâncias biologicamente ativas (SBA), para sua posterior extração como substâncias candidatas a serem geroprotetoras. Para especificar a eficácia dos parâmetros selecionados de cultivo em cultura de células, foi realizada a análise de crescimento de biomassa para culturas de calos e raízes, índice de crescimento, taxa de crescimento específica e viabilidade para culturas em suspensão. Os resultados do estudo possibilitaram a seleção do meio nutriente para o cultivo de células de Ulmária. Verificou-se que, quanto maior a atividade antioxidante dos extratos, maiores eram as propriedades antimicrobianas exibidas. Neste estudo, culturas celulares in vitro e extratos alcoólicos da planta Filipendula ulmaria foram considerados matérias-primas ricas em substâncias candidatas a serem geroprotetoras. De acordo com os dados obtidos, a planta é rica em ácidos hidroxibenzoico e salicílico, espirosídeo, avicularina e hiperosídeo.

Nicotinamide riboside intervention alleviates hematopoietic system injury of ionizing radiation-induced premature aging mice.

Radiotherapy destroys cancer cells and inevitably harms normal human tissues, causing delayed effects of acute radiation exposure (DEARE) and accelerating the aging process in most survivors. However, effective methods for preventing premature aging induced by ionizing radiation are lacking. In this study, the premature aging mice of DEARE model was established after 6 Gy total body irradiation (TBI). Then the therapeutic effects and mechanism of nicotinamide riboside on the premature aging mice were evaluated. The results showed that 6 Gy TBI induced premature aging of the hematopoietic system in mice. Nicotinamide riboside treatment reversed aging spleen phenotypes by inhibiting cellular senescence and ameliorated serum metabolism profiles. Further results demonstrated that nicotinamide riboside supplementation alleviated the myeloid bias of hematopoietic stem cells and temporarily restored the regenerative capacity of hematopoietic stem cells probably by mitigating the reactive oxygen species activated GCN2/eIF2α/ATF4 signaling pathway. The results of this study firstly indicate that nicotinamide riboside shows potential as a DEARE therapeutic agent for radiation-exposed populations and patients who received radiotherapy.

Theaflavin-3,3'-digallate ameliorates learning and memory impairments in mice with premature brain aging induced by D-galactose.

Age-related neurodegenerative diseases accompanied by learning and memory deficits are growing in prevalence due to population aging. Cellular oxidative stress is a common pathomechanism in multiple age-related disorders, and various antioxidants have demonstrated therapeutic efficacy in patients or animal models. Many plants and plant extracts possess potent antioxidant activity, but the compounds responsible are frequently unknown. Identification and evaluation of these phytochemicals is necessary for optimal targeted therapy. A recent study identified theaflavin-3,3'-digallate (TFDG) as the most potent among a large series of phytochemical antioxidants. Here we examined if TFDG can mitigate learning and memory impairments in the D-galactose model of age-related neurodegeneration. Experimental mice were injected subcutaneously with D-galactose (120 mg/kg) for 56 days. In treatment groups, different doses of TFDG were administered daily by gavage starting on day 29 of D-galactose injection. Model mice exhibited poor learning and memory in the novel object recognition and Y-maze tests, reduced brain/body mass ratio, increased brain glutamate concentration and acetylcholinesterase activity, decreased brain acetylcholine concentration, and lower choline acetyltransferase, glutaminase, and glutamine synthetase activities. Activities of antioxidant enzymes glutathione peroxidase and superoxide dismutase were also reduced, while the concentration of malondialdehyde, a lipid peroxidation product, was elevated. Further, antioxidant genes Nrf2, Prx2, Gsh-px1, and Sod1 were downregulated in brain. Each one of these changes was dose-dependently reversed by TFDG. TFDG is an effective antioxidant response inducer and neuroprotectant that can restore normal neurotransmitter metabolism and ameliorate learning and memory dysfunction in the D-galactose model of age-related cognitive decline.

Worker bees (Apis mellifera) deprived of pollen in the first week of adulthood exhibit signs of premature aging.

Pollinator populations, including bees, are in rapid decline in many parts of the world, raising concerns over the future of ecosystems and food production. Among the factors involved in these declines, poor nutrition deserves attention. The diet consumed by adult worker honeybees (Apis mellifera) is crucial for their behavioral maturation, i.e., the progressive division of labor they perform, such as nurse bees initially and later in life as foragers. Poor pollen nutrition is known to reduce the workers' lifespan, but the underlying physiological and genetic mechanisms are not fully understood. Here we investigate how the lack of pollen in the diet of workers during their first week of adult life can affect age-related phenotypes. During the first seven days of adult life, newly emerged workers were fed either a pollen-deprived (PD) diet mimicking that of an older bee, or a control pollen-rich (PR) diet, as typically consumed by young bees. The PD-fed bees showed alterations in their fat body transcriptome, such as a switch from a protein-lipid based metabolism to a carbohydrate-based metabolism, and a reduced expression of genes involved with immune response. The absence of pollen in the diet also led to an accumulation of oxidative stress markers in fat body tissue and alterations in the cuticular hydrocarbon profiles, which became similar to those of chronologically older bees. Together, our data indicate that the absence of pollen during first week of adulthood triggers the premature onset of an aging-related worker phenotype.

Diesel Particulate Extract Accelerates Premature Skin Aging in Human Fibroblasts via Ceramide-1-Phosphate-Mediated Signaling Pathway.

Both intrinsic (i.e., an individual's body clock) and extrinsic factors (i.e., air pollutants and ultraviolet irradiation) accelerate premature aging. Epidemiological studies have shown a correlation between pollutant levels and aging skin symptoms. Diesel particle matter in particular leads to some diseases, including in the skin. Our recent study demonstrates that diesel particulate extract (DPE) increases apoptosis via increases in an anti-mitogenic/pro-apoptotic lipid mediator, ceramide in epidermal keratinocytes. Here, we investigated whether and how DPE accelerates premature skin aging using cultured normal human dermal fibroblasts (HDF). We first demonstrated that DPE increases cell senescence marker ß-galactosidase activity in HDF. We then found increases in mRNA and protein levels, along with activity of matrix metalloprotease (MMP)-1 and MMP-3, which are associated with skin aging following DPE exposure. We confirmed increases in collagen degradation in HDF treated with DPE. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) is activated by DPE and results in increased ceramide production by sphingomyelinase activation in HDF. We identified that ceramide-1-phosphate (C1P) (produced from ceramide by ceramide kinase activation) activates MMP-1 and MMP-3 through activation of arachidonate cascade, followed by STAT 1- and STAT 3-dependent transcriptional activation.

Síndrome de Werner: relato de caso / Werner's syndrome: case report / Síndrome de Werner: reporte de un caso

Introdução: Síndrome de Werner, doença autossômica recessiva, tem como característica o envelhecimento precoce e acelerado. Objetivo: Descrever a evolução clínica favorável da síndrome de Werner em paciente acompanhada periodicamente no ambulatório de geriatria para promover atenção ao processo de envelhecimento por meio de abordagem preventiva e tratamento precoce das alterações que caracterizam a doença. Material e Método: Paciente de 31 anos de idade, sexo feminino, admitida no ambulatório de Aconselhamento Genético de um hospital-escola do noroeste paulista, apresentando baixa estatura, ulcerações, dor em região plantar e dificuldade para deambular, alterações cutâneas pigmentares com fissuras e ressecamento de toda a pele, além de cabelos grisalhos e quebradiços, catarata bilateral, hipotireoidismo e osteoporose. Tinha antecedentes familiares compatíveis com pais consanguíneos, um casal de irmãos hígidos e mãe com histórico de ocorrência de dois abortos espontâneos consecutivos. Apresentava, portanto, critérios diagnósticos para síndrome de Werner. Foi tratada nos ambulatórios de geriatria, endocrinologia, dermatologia, oftalmologia e ortopedia da mesma Instituição. Resultado: O tratamento consistiu na remoção cirúrgica de catarata, uso de levotiroxina 75 mcg/dia e de creme hidratante para pele (ácido salicílico 20% e vaselina sólida 30g), calçado ortopédico para pé neuropático com solado em EVA de média compressão, antiderrapante, confeccionado sob medida. Houve melhora na sintomatologia, especialmente quanto à deambulação com as medidas terapêuticas adotadas. Conclusão: A avaliação interdisciplinar inicial da paciente foi fundamental, pois possibilitou a elaboração precoce do diagnóstico e o acompanhamento no ambulatório de geriatria, promovendo maior atenção ao processo de envelhecimento preconizado por uma abordagem preventiva e tratamento subsequente das alterações que caracterizam a síndrome de Werner.(AU)

Introduction: Werner syndrome, an autosomal recessive disease, is characterized by premature and accelerated aging. Objective: To describe the favorable clinical evolution of Werner's syndrome in a patient periodically followed in the geriatric outpatient clinic to promote attention to the aging process through a preventive approach and early treatment of the changes that characterize the disease. Material and Method: A 31-year-old female patient, admitted to the Genetic Counseling outpatient clinic of a school hospital in northwestern pigmentary skin changes with cracks and dryness of the entire skin, as well as gray and brittle hair, bilateral cataract, hypothyroidism and osteoporosis. She had a family history compatible with consanguineous parents, a couple of healthy siblings and a mother with a history of two consecutive miscarriages. It therefore presented diagnostic criteria for Werner syndrome. She was treated in geriatric, endocrinology, dermatology, ophthalmology and orthopedics clinics of the same institution. Result: The treatment consisted of surgical removal of cataract, use of levothyroxine 75 mcg/day and moisturizing cream for skin (salicylic acid 20% and solid petroleum jelly 30g), orthopedic footwear for neuropathic foot anti-slip, made to measure. There was improvement in symptomatology, especially regarding ambulation with the therapeutic measures adopted. Conclusion: The initial interdisciplinary evaluation of the patient was fundamental, since it enabled the early preparation of the diagnosis and the follow-up in the geriatric outpatient clinic, promoting greater attention to the aging process recommended by a preventive approach and subsequent treatment of the changes that characterize Werner's syndrome.(AU)

Introducción: El síndrome de Werner, una enfermedad autosómica recesiva, se caracteriza por un envejecimiento prematuro y acelerado. Objetivo: Describir la evolución clínica favorable del síndrome de Werner en un paciente en seguimiento periódico en la consulta externa de geriatría para promover la atención al proceso de envejecimiento a través de un abordaje...(AU)

Evaluation of the Anti-Aging Effects of a Probiotic Combination Isolated From Centenarians in a SAMP8 Mouse Model.

Population aging is a prominent global problem in today's society. However, there are currently no good methods to treat or prevent aging, so anti-aging research has crucial implications. In this research, we screened bacteria from centenarians, and finally selected four probiotics (Lactobacillus fermentum SX-0718, L. casei SX-1107, Bifidobacterium longum SX-1326, and B. animalis SX-0582) to form a probiotic combination. By using the senescence accelerated mouse prone 8 (SAMP8) model, the anti-aging effects of the probiotic combination were evaluated by using behavioural testing, neuroinflammation, intestinal inflammation, and intestinal microbiota. The results showed that probiotic combination improved the impaired spatial memory, motor dysfunction, and decreased exploratory behavior in aging mice. The probiotic combination inhibited Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NFκB)-induced neuroinflammation and up-regulated the expression of Sirt 1 to protect hippocampal neurons. At the same time, the probiotic combination regulated the intestinal microbiota, reduced the relative abundance of Alistipes and Prevotella in SAMP8 mice, inhibited TLR4/NFκB-induced intestinal inflammation, and increased the expression of intestinal permeability related proteins zonula occludens-1 (ZO-1) and Occuldin. The anti-aging effects of the probiotic combination may be through the regulating intestinal microbiota and inhibiting TLR4/NFκB-induced inflammation. This research provides the basis and technical support for the future production and application of the probiotic combination.

Antiaging Effects of Vicatia thibetica de Boiss Root Extract on Caenorhabditis elegans and Doxorubicin-Induced Premature Aging in Adult Mice.

The roots of Vicatia thibetica de Boiss are a kind of Chinese herb with homology of medicine and food. This is the first report showing the property of the extract of Vicatia thibetica de Boiss roots (HLB01) to extend the lifespan as well as promote the healthy parameters in Caenorhabditis elegans (C. elegans). For doxorubicin- (Doxo-) induced premature aging in adult mice, HLB01 counteracted the senescence-associated biomarkers, including P21 and γH2AX. Interestingly, HLB01 promoted the expression of collagen in C. elegans and mammalian cell systemically, which might be one of the essential factors to exert the antiaging effects. In addition, HLB01 was also found as a scavenger of free radicals, thereby performing the antioxidant ability. Lifespan extension by HLB01 was also dependent on DAF-16 and HSF-1 via oxidative stress resistance and heat stress resistance. Taken together, overall data suggested that HLB01 could extend the lifespan and healthspan of C. elegans and resist Doxo-induced senescence in mice via promoting the expression of collagen, antioxidant potential, and stress resistance.

Spectroscopic Signature of Red Blood Cells in a D-Galactose-Induced Accelerated Aging Model.

This work presents a semi-quantitative spectroscopic approach, including FTIR-ATR and Raman spectroscopies, for the biochemical analysis of red blood cells (RBCs) supported by the biochemical, morphological and rheological reference techniques. This multi-modal approach provided the description of the RBC alterations at the molecular level in a model of accelerated aging induced by administration of D-galactose (D-gal), in comparison to natural aging. Such an approach allowed to conclude that most age-related biochemical RBC membrane changes (a decrease in lipid unsaturation and the level of phospholipids, or an increase in acyl chain shortening) as well as alterations in the morphological parameters and RBC deformability are well reflected in the D-gal model of accelerated aging. Similarly, as in natural aging, a decrease in LDL level in blood plasma and no changes in the fraction of glucose, creatinine, total cholesterol, HDL, iron, or triglycerides were observed during the course of accelerated aging. Contrary to natural aging, the D-gal model led to an increase in cholesterol esters and the fraction of total esterified lipids in RBC membranes, and evoked significant changes in the secondary structure of the membrane proteins. Moreover, a significant decrease in the phosphorous level of blood plasma was specific for the D-gal model. On the other hand, natural aging induced stronger changes in the secondary structures of the proteins of the RBCs' interior. This work proves that research on the aging mechanism, especially in circulation-related diseases, should employ the D-gal model with caution. Nonetheless, the D-gal model enables to imitate age-related rheological alterations in RBCs, although they are partially derived from different changes observed in the RBC membrane at the molecular level.

eIF5A hypusination, boosted by dietary spermidine, protects from premature brain aging and mitochondrial dysfunction.

Mitochondrial function declines during brain aging and is suspected to play a key role in age-induced cognitive decline and neurodegeneration. Supplementing levels of spermidine, a body-endogenous metabolite, has been shown to promote mitochondrial respiration and delay aspects of brain aging. Spermidine serves as the amino-butyl group donor for the synthesis of hypusine (Nε-[4-amino-2-hydroxybutyl]-lysine) at a specific lysine residue of the eukaryotic translation initiation factor 5A (eIF5A). Here, we show that in the Drosophila brain, hypusinated eIF5A levels decline with age but can be boosted by dietary spermidine. Several genetic regimes of attenuating eIF5A hypusination all similarly affect brain mitochondrial respiration resembling age-typical mitochondrial decay and also provoke a premature aging of locomotion and memory formation in adult Drosophilae. eIF5A hypusination, conserved through all eukaryotes as an obviously critical effector of spermidine, might thus be an important diagnostic and therapeutic avenue in aspects of brain aging provoked by mitochondrial decline.

Reductions in Gray Matter Linked to Epigenetic HIV-Associated Accelerated Aging.

A growing literature suggests a relationship between HIV-infection and a molecular profile of age acceleration. However, despite the widely known high prevalence of HIV-related brain atrophy and HIV-associated neurocognitive disorder (HAND), epigenetic age acceleration has not been linked to HIV-related changes in structural MRI. We applied morphological MRI methods to study the brain structure of 110 virally suppressed participants with HIV infection and 122 uninfected controls age 22-72. All participants were assessed for cognitive impairment, and blood samples were collected from a subset of 86 participants with HIV and 83 controls to estimate epigenetic age. We examined the group-level interactive effects of HIV and chronological age and then used individual estimations of epigenetic age to understand the relationship between age acceleration and brain structure. Finally, we studied the effects of HAND. HIV-infection was related to gray matter reductions, independent of age. However, using epigenetic age as a biomarker for age acceleration, individual HIV-related age acceleration was associated with reductions in total gray matter. HAND was associated with decreases in thalamic and hippocampal gray matter. In conclusion, despite viral suppression, accentuated gray matter loss is evident with HIV-infection, and greater biological age acceleration specifically relates to such gray matter loss.

The relationship of CCL4, BCL2A1, and NFKBIA genes with premature aging in women of Yin deficiency constitution.

BACKGROUND: Traditional Chinese Medicine (TCM) defined constitution as a health statue or physical fitness that determines individual susceptibility to diseases. Yin deficiency constitution (YinDC) is a type of constitution closely related to aging. Previous studies found that the characteristic genes of YinDC are part of the inflammatory aging signaling pathways (e.g., NF-kappa B). Therefore, the aim of the study was to further reveal the dysregulation of genes associated with inflammatory aging in YinDC women. METHODS: This study adopted the industrial standard of constitutional judgment, and screened YinDC (n = 30) and Balanced constitution (BC) (n = 30) from women between the ages of 35 to 49, a range categorized as the degenerating period by TCM. Five genes CCL4, BCL2A1, NFKBIA, TAK1, and IL-8 were analyzed by qRT-PCR. RESULTS: Logistical regression revealed the correlation between body constitution and the expression of the five genes: the expression of NFKBIA and CCL4 mRNA was significantly up-regulated, whereas the expression of BCL2A1 mRNA was significantly down-regulated in YinDC (P < 0.05). Age or weight, when included in the model, did not affected the correlations. CONCLUSION: Increased mRNA expression of CCL4 and NFKBIA and decreased mRNA expression of BCL2A1 may be the molecular basis of premature aging of YinDC women. These results provide a mechanistic basis for early conditioning of YinDC, anti-aging, and the prevention of aging-related diseases.

In vitro activity and formulation of a flavonoid-containing cashew pulp extract for the topical treatment of acne and the protection of skin against premature aging.

The cashew nut is an important product in Brazil, both for consumption and export, with the pulp of the cashew fruit being considered a by-product despite its high flavonoid content. In this study, the use of cashew pulp extract as a treatment for acne and in the prevention of early skin damage was investigated. Its flavonoid content was determined using spectrophotometric identification, and its effects on cell and bacterial viability, the migration of keratinocytes, and antioxidant activity in vitro were evaluated. Furthermore, it was incorporated into an emulsion for topical administration, and the physical-chemical stability parameters of the formulation were determined. The cashew pulp contained flavonoids with healing and antioxidant activity, and was not toxic to keratinocyte cells in a viability test. The flavonoid-rich formulation was stable, indicating that this is a promising formulation for use in the treatment of acne and protection of skin against premature damage.[Figure: see text].

The Psilocybin-Telomere Hypothesis: An empirically falsifiable prediction concerning the beneficial neuropsychopharmacological effects of psilocybin on genetic aging.

We introduce a novel hypothesis which states that the therapeutic utilisation of psilocybin has beneficial effects on genetic aging. Ex hypothesi, we predict a priori that controlled psilocybin interventions exert quantifiable positive impact on leucocyte telomere length (telomeres are a robust predictor of mortality and multifarious aging-related diseases). Our hypothesising follows the Popperian logic of scientific discovery, viz., bold (and refutable) conjectures form the very foundation of scientific progress. The 'psilocybin-telomere hypothesis' is formalised as a logically valid deductive (syllogistic) argument and we provide substantial evidence to support the underlying premises. Impetus for our theorising derives from a plurality of converging empirical sources indicating that psilocybin has persistent beneficial effects on various aspects of mental health (e.g., in the context of depression, anxiety, PTSD, OCD, addiction, etc.). Additional support is based on a large corpus of studies that establish reliable correlations between mental health and telomere attrition (improved mental health is generally correlated with longer telomeres). Another pertinent component of our argument is based on recent studies which demonstrate that "meditative states of consciousness" provide beneficial effects on genetic aging. Similarly, psilocybin can induce states of consciousness that are neurophysiologically and phenomenologically significantly congruent with meditative states. Furthermore, prior research has demonstrated that a single dose of psilocybin can occasion life-changing transformative experiences (≈ 70% of healthy volunteers rate their experience with psilocybin amongst the five personally most meaningful lifetime events, viz., ranked next to giving birth to a child or losing a loved one). We postulate that these profound psychological events leave quantifiable marks at the molecular genetic/epigenetic level. Given the ubiquitous availability and cost effectiveness of telomere length assays, we suggest that quantitative telomere analysis should be regularly included in future psilocybin studies as an adjunctive biological marker (i.e., to facilitate scientific consilience via methodological triangulation). In order to substantiate the 'psilocybin-telomere hypothesis' potential neuropsychopharmacological, endocrinological, and genetic mechanisms of action are discussed (e.g., HPA-axis reactivity, hippocampal neurogenesis, neurotropic growth factors such as BDNF, 5-HT2A receptor agonism, neuroplasticity/synaptoplasticity, brain-wide alterations in neuronal functional connectivity density, involvement of the SLC6A4 serotonin transporter gene, inter alia). The proposed research agenda is thus intrinsically highly interdisciplinary, and it has deep ramifications from a philosophy of science perspective as it connects the epistemic level (qualitative experiential phenomenology) with the ontic level (quantitative molecular genetics) of analysis. In the long term, multidisciplinary and innovative investigations of the 'psilocybin-telomere hypothesis' could contribute to the improvement of senotherapeutic psychological interventions and the identification of novel geroprotective and neuroprotective/restorative pharmaceutical targets to decelerate genetic aging and improve well-being and quality of life during the aging process.

Methyl-Hispolon from Phellinus lonicerinus (Agaricomycetes) Affects Estrogen Signals in MCF-7 Breast Cancer Cells and Premature Aging in Rats.

We studied Phellinus lonicerinus to determine the cytotoxic effect and the dual estrogenic activities of methyl-hispolon and their relation to estrogen signals in vivo and in vitro. The Glide scores of methyl-hispolon-estrogen receptor α (ERα) and methyl-hispolon-ERß docked complexes were -7.29 kcal/mol and -6.68 kcal/mol in docking simulations. Methyl-hispolon had a significant antiproliferative effect for estrogen-sensitive ER(+) MCF-7 cells in the absence of estrogen, and it exhibited dual estrogen activities. Methyl-hispolon increased the serum E2 in rats with premature ovarian failure and fulfilled the estrogenic function in the uterus and ovary. Methyl-hispolon significantly inhibited the expression of Ras, API, ERα, C-myc, and cyclinDl, as well as their gene transcription in RL95-2 cells. The phosphorylation of ERK1/2 was inhibited by methyl-hispolon. Thus, methyl-hispolon has potential use in treating estrogen deficiency-related diseases, with good antitumor effects and estrogenic activity.

[Optimizing nutrition of older people as a mean of preventing premature aging].

The review presents data on the characteristics of construction of the diet of older persons. It is shown that inadequate nutrition is a significant risk factor for cardiovascular diseases, obesity, type 2 diabetes mellitus, gout and others that contribute to premature aging. Optimization of the diet should be considered as one of the areas of prevention and rehabilitation of these diseases and the prevention of premature aging. Attention is drawn to the age peculiar properties of the energy value of the diet, the content and the ratio of macronutrients in it. Modern data on the recommended daily intake of micronutrients -vitamins, minerals and trace elements for the elderly are presented. From the positions of the theory of oxidative stress, chronic inflammation and high-calorie nutrition, it is considered expedient to include products containing antioxidant ingredients: vitamins, trace elements and minor biologically active food components in the diet.

Premature Physiologic Aging as a Paradigm for Understanding Increased Risk of Adverse Health Across the Lifespan of Survivors of Childhood Cancer.

The improvement in survival of childhood cancer observed across the past 50 years has resulted in a growing acknowledgment that simply extending the lifespan of survivors is not enough. It is incumbent on both the cancer research and the clinical care communities to also improve the health span of survivors. It is well established that aging adult survivors of childhood cancer are at increased risk of chronic health conditions, relative to the general population. However, as the first generation of survivors age into their 50s and 60s, it has become increasingly evident that this population is also at risk of early onset of physiologic aging. Geriatric measures have uncovered evidence of reduced strength and speed and increased fatigue, all components of frailty, among survivors with a median age of 33 years, which is similar to adults older than 65 years of age in the general population. Furthermore, frailty in survivors independently increased the risk of morbidity and mortality. Although there has been a paucity of research investigating the underlying biologic mechanisms for advanced physiologic age in survivors, results from geriatric populations suggest five biologically plausible mechanisms that may be potentiated by exposure to cancer therapies: increased cellular senescence, reduced telomere length, epigenetic modifications, somatic mutations, and mitochondrial DNA infidelity. There is now a critical need for research to elucidate the biologic mechanisms of premature aging in survivors of childhood cancer. This research could pave the way for new frontiers in the prevention of these life-changing outcomes.

Natural antioxidants in prevention of accelerated ageing: a departure from conventional paradigms required.

The modern lifestyle is characterised by various factors that cause accelerating ageing by the upregulation of oxidative stress and inflammation-two processes that are inextricably linked in an endless circle of self-propagation. Inflammation in particular is commonly accepted as aetiological factor in many chronic disease states, such as obesity, diabetes and depression. In terms of disease prevention or treatment, interventions aimed at changing dietary and/or exercise habits have had limited success in practise, mostly due to poor long-term compliance. Furthermore, other primary stimuli responsible for eliciting an oxidative stress or inflammatory response-e.g. psychological stress and anxiety-cannot always be easily addressed. Thus, preventive medicine aimed at countering the oxidative stress and/or inflammatory responses has become of interest. Especially in developing countries, such as South Africa, the option of development of effective strategies from plants warrants further investigation. A brief overview of the most relevant and promising South African plants which have been identified in the context of inflammation, oxidative stress and chronic disease is provided here. In addition, and more specifically, our group and others have shown considerable beneficial effects across many models, after treatment with products derived from grapes. Of particular interest, specific cellular mechanisms have been identified as therapeutic targets of grape-derived polyphenols in the context of inflammation and oxidative stress. The depth of these studies afforded some additional insights, related to methodological considerations pertaining to animal vs. human models in natural product research, which may address the current tendency for generally poor translation of positive animal model results into human in vivo models. The importance of considering individual data vs. group averages in this context is highlighted.

Effects of Bushen-Yizhi formula on age-related inflammation and oxidative stress in senescence-accelerated mice.

The present study aimed to investigate the possible effects and underlying molecular mechanism of Bushen­Yizhi formula (BSYZ), a traditional Chinese medicine, on age­related degeneration of brain physiology in senescence­accelerated mouse prone 8 (SAMP8) mice. SAMP8 mice (age, 6 months) were administered BSYZ (1.46, 2.92 and 5.84 g/kg/day) for 30 days. Morris water maze and step­down tests demonstrated that BSYZ significantly improved memory impairments in SAMP8 mice. In addition, BSYZ significantly enhanced the expression levels of peroxisome proliferator­activated receptor­Î³ and B­cell lymphoma extra­large, and downregulated the expression levels of inflammatory mediators, glial fibrillary acidic protein, cyclooxygenase­2, nuclear factor­κB and interleukin­1ß in the brain compared with untreated SAMP8 mice. Furthermore, BSYZ reversed disordered superoxide dismutase activity, malondialdehyde content and glutathione peroxidase activity, and ameliorated apoptosis and histological alterations. The present study indicated that BSYZ may attenuate cognitive impairment in SAMP8 mice, and modulate inflammation, oxidative stress and neuronal apoptosis. These results suggested that BSYZ may have the potential to be further developed into a therapeutic agent for protection against age­related neurodegenerative diseases.