Properties of Resveratrol:In VitroandIn VivoStudies about Metabolism, Bioavailability, and Biological Effects in Animal Models and Humans

Plants containing resveratrol have been used effectively in traditional medicine for over 2000 years. It can be found in some plants, fruits, and derivatives, such as red wine. Therefore, it can be administered by either consuming these natural products or intaking nutraceutical pills. Resveratrol exhibits a wide range of beneficial properties, and this may be due to its molecular structure, which endow resveratrol with the ability to bind to many biomolecules. Among these properties its activity as an anticancer agent, a platelet antiaggregation agent, and an antioxidant, as well as its antiaging, antifrailty, anti-inflammatory, antiallergenic, and so forth activities, is worth highlightin…

Response to Vidal and Colleagues

Higher oxidative stress in human dental pulp stem cells cultured at 21% O2 compared to 5% O2

Centenarians overexpress BCL-xL, which confers them a protection against apoptosis, oxidative stress and immunosenescence

Centenarians not only have an extraordinary longevity, but also show a compression of morbidity. They preserve the capacity of maintaining homeostasis, and this is the reason for them to reach such a long life. We studied their mRNA expression profile and identified 1721 mRNAs differentially expressed by centenarians when compared with septuagenarians and young people. A sub-network analysis showed six common genes: interferon, T-cell receptor, tumor necrosis factor, SP1 transcription factor, transforming growth factor and IL-32.These six centenarian-specific genes are related to Bcl-xL, Fas, and Fas ligand all of them involved in the control of apoptosis. RT-PCR analysis confirmed that cen…

Clearing Amyloid-β Through PPARγ/ApoE Activation by Genistein is an Experimental Treatment of Alzheimer's Disease

Amyloid-β (Aβ) clearance from brain, which is decreased in Alzheimer’s disease, is facilitated by apolipoprotein E. Apo E is up-regulated by activation of the retinoid X receptor moiety of the RXR/PPARγ dimeric receptor. Genistein, a non-toxic, well tested and inexpensive drug has a multifaceted protective effect: antioxidant (because it stimulates the expression of antioxidant genes), anit-inflammatory and stimulator of activates the PPARγ receptor, which results in increased expression of ApoE. Treatment of an Alzheimer’s mouse model with genistein results in a remarkable and rapid improvement in various parameters of cognition, such as hippocampal learning, recognition memory, implicit m…

Influence of partial O 2 pressure on the adhesion, proliferation, and osteogenic differentiation of human dental pulp stem cells on β-tricalcium phosphate scaffold

Our purpose was to analyse the influence of O2 pressure on the adhesion, proliferation, and osteogenic differentiation of human dental pulp stem cells (DPSC) on 3-tricalcium phosphate (3-TCP) scaffold. DPSC isolated from extracted third molars were seeded on 3-TCP and cultured under 3% or 21% O2 pressure. Cell adhesion, proliferation, and differentiation over the biomaterial were evaluated at 7, 13, 18, and 23 days of culture. Cell adhesion was determined by light microscopy, proliferation by DNA quantification, and osteogenic differentiation by alkaline phosphatase activity analysis. All DPSC adhered to 3-TCP with both O2 conditions. Cell proliferation values were higher at 3% O2 in each t…

Targeting Alzheimer’s disease with multimodal polypeptide-based nanoconjugates

LRP1-targeted St-Cl–polyglutamate conjugates as multivalent neuroprotective/neurotrophic therapeutics for Alzheimer’s disease.

Centenarian offspring: A model for understanding healthy aging

Centenarians exhibit extreme longevity showing a compression of morbidity. We showed previously that microRNA expression profiles and plasma protein carbonylation in centenarians and young people are similar, whereas they are very different from that found in old individuals. This suggests that centenarians have a better control of homeostasis and are protected against oxidative damage. In this study, we aimed to determine if such characteristic microRNA expression profile and lower protein oxidation status in centenarians may be inherited by their offspring. For this purpose, we collected plasma and peripheral blood mononuclear cells from 90 septuagenarians, 68 centenarians and 46 centenar…

La sobreexpresión de Fas en moscas aumenta su supervivencia

Brain-Derived Neurotrophic Factor as a Marker of Cognitive Frailty.

Antioxidant role of microvesicles, activated by genistein, in stem cells

Intercellular communication is an essential hallmark of multicellular organisms. Microvesicles (MVs), which are released from and taken up by most types of cells are involved in intercellular communication. The nutrients we ingest from food contact with immune cells in the bloodstream and can promote the formation of MVs. Some foods contain molecules with regulatory activity, such as genistein, a polyphenol found in soy. We aimed to study the effects of MVs released from genistein-treated immune cells on dental pulp stem cells (DPSC). We obtained peripheral blood mononuclear cells (PBMC) from 5 young women (aged 18–25). Cells were cultured and treated with 0.5 μM genistein or 0.01% DMSO as …

El resveratrol induce catabolismo lipídico en ratones C57Bl/6

AB1367-HPR EFFECTIVENESS OF THE HYPERBARIC TREATMENT ON THE PERCEIVED PAIN, FATIGUE AND FUNCTIONALITY OF WOMEN WITH FIBROMYALGIA

Background Fibromyalgia (FM) is a chronic pain syndrome accompanied by other symptoms such as fatigue or altered functionality1. One of the most common non-pharmacologic treatment is physical exercise because of its known positive influence on pain as a consequence of the physical condition improvement. 2 However, they use to present a lack of adherence to this type of therapeutic programs may be attributable to post-exercise pain 3. For this reason, alternative approaches that do not involve physical efforts, such as hyperbaric therapy, may be effective to reduce pain, fatigue or functionality in women with FM.4 Objectives To compare the effectiveness of hyperbaric therapy and physical exe…

Los descendientes de centenarios como modelo de envejecimiento saludable

Pharmacological properties of physical exercise in the elderly.

Scientific evidence links physical activity to several benefits. Recently, we proposed the idea that exercise can be regarded as a drug. As with many drugs, dosage is of great importance. However, to issue a public recommendation of physical activity in aging is not an easy task. Exercise in the elderly needs to be carefully tailored and individualized with the specific objectives of the person or group in mind. The beneficial effects of exercise in two of the main age-related diseases, sarcopenia and Alzheimer's Disease, are dealt with at the beginning of this report. Subsequently, dosage of exercise and the molecular signaling pathways involved in its adaptations are discussed. Exercise a…

Validación de la carbonilación proteica como biomarcador de fragilidad

Small extracellular vesicles from young mice prevent frailty, improve healthspan and decrease epigenetic age in old mice

SummaryAging is associated with an increased risk of frailty, disability, comorbidities, institutionalization, falls, fractures, hospitalization, and mortality. Searching for strategies to delay the degenerative changes associated with aging and frailty is interesting. We treated old animals intravenously with small extracellular vesicles (sEVs) derived from adipose mesenchymal stem cells (ADSCs) of young animals, and we found an improvement of several functional parameters usually altered with aging, such as motor coordination, grip strength, fatigue resistance, fur regeneration, and renal function. Frailty index analysis showed that 40% of old control mice were frail, whereas none of the …

Extracellular Vesicles from Healthy Cells Improves Cell Function and Stemness in Premature Senescent Stem Cells by miR-302b and HIF-1α Activation.

Aging is accompanied by the accumulation of senescent cells that alter intercellular communication, thereby impairing tissue homeostasis and reducing organ regenerative potential. Recently, the administration of mesenchymal stem cells (MSC)-derived extracellular vesicles has proven to be more effective and less challenging than current stem cell-based therapies. Extracellular vesicles (EVs) contain a cell-specific cargo of proteins, lipids and nucleic acids that are released and taken up by probably all cell types, thereby inducing functional changes via the horizontal transfer of their cargo. Here, we describe the beneficial properties of extracellular vesicles derived from non-senescent M…

Active paraplegics are protected against exercise-induced oxidative damage through the induction of antioxidant enzymes

Exercise improves functional capacity in spinal cord injury (SCI). However, exhaustive exercise, especially when sporadic, is linked to the production of reactive oxygen species that may have a detrimental effect on SCI. We aimed to study the effect of a single bout of exhaustive exercise on systemic oxidative stress parameters and on the expression of antioxidant enzymes in individuals with paraplegia. The study was conducted in the Physical Therapy department and the Physical Education and Sports department of the University of Valencia. Sixteen paraplegic subjects were submitted to a graded exercise test (GET) until volitional exhaustion. They were divided into active or non-active group…

Centenarians maintain miRNA biogenesis pathway while it is impaired in octogenarians.

Centenarians but not octogenarians up regulate the expression of miRNAs, as we previously reported. We have looked into miRNA biogenesis. We show that RNA POL II, DROSHA, EXPORTIN 5 and DICER, are up-regulated in centenarians compared with octogenarians. Furthermore, factors involved in the control of these miRNAs biogenesis genes are also up-regulated in centenarians. Therefore, the up-regulation of miRNA expression in centenarians can be explained in part because miRNA biogenesis pathway is depressed in octogenarians (ordinary aging) while it is maintained in centenarians (extraordinary aging).

Sarcopenia, frailty and their prevention by exercise.

Sarcopenia is a major component of the frailty syndrome, both being considered as strong predictors of morbidity, disability, and death in older people. In this review, we explore the definitions of sarcopenia and frailty and summarize the current knowledge on their relationship with oxidative stress and the possible therapeutic interventions to prevent or treat them, including exercise-based interventions and multimodal strategies. We highlight the relevance of the impairment of the nervous system and of the anabolic response (protein synthesis) in muscle aging leading to frailty and sarcopenia. We also discuss the importance of malnutrition and physical inactivity in these geriatric syndr…

Effect of low-impact aerobic exercise combined with music therapy on patients with fibromyalgia. A pilot study.

Abstract Objective Fibromyalgia is a pathological entity characterized by chronic widespread musculoskeletal pain and the presence of "tender points". It constitutes a significant health problem because of its prevalence and economic impact. The aim of the present study was to determine the therapeutic benefits of low impact aerobic exercise alone or in combination with music therapy in patients with fibromyalgia. Methods A single-blind randomized controlled pilot trial was performed. Thirty-five individuals with fibromyalgia were divided into three groups: (G1) therapeutic aerobic exercise with music therapy (n=13); (G2) therapeutic aerobic exercise at any rhythm (n=13) and (CG) control (n…

Drosophila melanogaster overexpression FAS live longer

FAS and FAS ligand is critical in the control of the extension of extrinsic pathway of apoptosis. In previous studies we have performed transcriptomics peripheral blood cells from centenarians, octogenarians and young persons and we found over expression in centenarians of the FAS receptor. To confirm the role of FAS ligand in longevity across animal species, we have generated Drosophila melanogaster that over expresses this gene using the GAL4-UAS technique. The results show that flies overexpressing FAS increase maximal longevity in twelve percent and average longevity in six percent. Therefore, we confirm that FAS is related to longevity flight.

Exceptional human longevity is associated with a specific plasma phenotype of ether lipids

A lipid profile resistant to oxidative damage is an inherent trait associated with animal lifespan. However, there is a lack of lipidomic studies on human longevity. Here we use mass spectrometry based technologies to detect and quantify 137 ether lipids to define a phenotype of healthy humans with exceptional lifespan. Ether lipids were chosen because of their antioxidant properties and ability to modulate oxidative stress. Our results demonstrate that a specific ether lipid signature can be obtained to define the centenarian state. This profile comprises higher level of alkyl forms derived from phosphatidylcholine with shorter number of carbon atoms and double bonds; and decreased content…

sj-pdf-1-cre-10.1177_02692155211022009 – Supplemental material for Effects of balance training on functionality, ankle instability, and dynamic balance outcomes in people with chronic ankle instability: Systematic review and meta-analysis

Supplemental material, sj-pdf-1-cre-10.1177_02692155211022009 for Effects of balance training on functionality, ankle instability, and dynamic balance outcomes in people with chronic ankle instability: Systematic review and meta-analysis by Sara Mollà-Casanova, Marta Inglés and Pilar Serra-Añó in Clinical Rehabilitation

The Relationship between Diet and Frailty in Aging

The increase in lifespan in the 20th century entails an increase in the elderly population. This brings a new challenge for society, causing people to have physical and mental limitations caused by age-related diseases, such as frailty. Frailty is clinically characterized by multisystem pathophysiological processes, such as chronic inflammation, immune activation, dysregulation of the musculoskeletal and endocrine systems, oxidative stress, energy imbalances, mitochondrial dysfunction, and sarcopenia. The elderly should consume energy in amounts close to those in what is currently accepted as a balanced diet. However, an increase in protein intake may be recommended for elderly people as l…

Resveratrol shifts energy metabolism to increase lipid oxidation in healthy old mice.

Abstract Objectives The objective of this work was to determine the specific mechanisms by which resveratrol inhibits lipogenesis and stimulates lipolysis. Methods Twelve male mice were individually introduced into a metabolic cage for 24 h to measure basal metabolic rate, prior to intervention. They were randomly divided into two groups, resveratrol (RSV) and control (C), and administered resveratrol intraperitoneally or vehicle, respectively, for two consecutive days. After 24 h, the metabolic energy expenditure was again determined for 24 h, before mice were sacrificed. Protein and gene expression of different enzymes related to metabolism in the hepatic tissue, adipose tissue and gastro…

Effects of balance training on functionality, ankle instability, and dynamic balance outcomes in people with chronic ankle instability: Systematic review and meta-analysis

Aim: To identify the effects of balance and strength training on function, ankle instability and dynamic balance in people with chronic ankle instability. Method: The search was conducted on randomized controlled trials that investigated the effects of balance training or strength training in people with chronic ankle instability compared to a control group. Therefore, a systematic electronic search was performed until April 2021 in Pubmed/MEDLINE, Cochrane, and Embase databases. Moreover, an additional search was further performed checking the reference lists of the selected articles. The main outcomes were ankle instability, functionality, and dynamic balance. Finally, a qualitative and q…

The importance of culturing primary cells under physiological conditions: proliferation, senescence, pluripotency

Mesenchymal stem cells (MSCs), such as human dental pulp stem cells (hDPSCs), are currently a source for cell therapy. However, cell therapy protocols require 10–400 million cells per treatment, and consequently, they need to be expanded in vitro before implantation, with the inconvenience that MSCs undergo senescence following a certain number of cell expansion passages, loosing their stem cell qualities. Ambient oxygen tension (21% pO2) is normally used for in vitro culture, but physiological levels in vivo range between 3% and 6% pO2. We previously demonstrated that hDPSC proliferation rate is significantly lowered at 21% pO2 due to enhanced oxidative stress, which led to the activation …

Centenarians: An excellent example of resilience for successful ageing.

Centenarians are remarkable not only because of their prolonged life, but also because they compress morbidity until the very last moments of their lives, thus being proposed as a model of successful, extraordinary ageing. From the medical viewpoint, centenarians do not escape the physiological decline or the age-related diseases or syndromes (i.e. frailty), but the rate of such processes is slow enough to be counterbalanced by their increased intrinsic capacity to respond to minor stresses of daily life (i.e. resilience). These new concepts are reviewed in this paper. Allostatic stresses lead to a chronic low-grade inflammation that has led to the proposal of the "inflammaging" theory of a…

Role of the aryl hydrocarbon receptor (AhR) signaling pathway in exceptional longevity in humans

Centenarians are the best example of successfully aging in humans. Thus, the characterization of the biological processes and pathways in this population is an excellent strategy to understand the lifespan extension. The aryl hydrocarbon receptor (AhR) is a ligand-activated-transcription factor historically known for regulating expression of several important drug-detoxifying proteins. But recently its role in the immune response and in cellular homeostasis has been recognized. Furthermore, AhR is activated in C. Elegans in extreme longevity due to a dietary restriction. We report here results of a whole transcriptome analysis of centenarians. The main biological process was the immune resp…

CENTENARIANS TRANSCRIPTOME IS UNIQUE AND REVEALS A ROLE OF BCL-XL IN SUCCESSFUL AGING

Centenarians not only enjoy an extraordinary aging, but also show a compression of morbidity. We identified 1721 mRNAs differentially expressed by PMBCs from centenarians when compared with septuagenarians and young people. Sub-network analysis led us to identify Bcl-xL as an important gene up-regulated in centenarians. We found that centenarians display lower plasma cytochrome C levels, higher mitochondrial membrane potential and also less cellular damage accumulation. Immune function is significantly impaired in septuagenarians compared with young people whereas centenarians maintain it. To further ascertain the functional role of Bcl-xL in cellular aging, we found in transduced lymphocyt…

Oxidative stress is related to frailty, not to age or sex, in a geriatric population

Age-associated frailty is a geriatric syndrome. Frail individuals are vulnerable and lack capacity to manage external stressors. Frailty is associated with oxidative stress, but it has not been addressed in a large controlled human cohort. We aimed to ascertain whether indicators of oxidative damage to lipids and proteins are biomarkers of frailty, after adjusting for age, sex, and other possible confounders. We measured lipid and protein oxidation in the Toledo Study for Healthy Aging participants (N=742, aged 65–95), classified as frail, prefrail and nonfrail according to the Fried criteria. We found that age- and sex-adjusted levels of MDA and protein carbonylation in plasma proved to be…

Physical Condition Factors that Predict a Better Quality of Life in Women with Fibromyalgia

What physical qualities can predict the quality of life (QoL) in women with fibromyalgia (FM)? QoL is a very complex outcome affected by multiple comorbidities in people with fibromyalgia. This study aims to determine which physical qualities can predict the quality of life in women with FM. Also, a comparison between the physical qualities of women with FM and healthy counterparts was conducted. In total, 223 women participated in this cross-sectional study, 123 with FM, with ages ranging between 45 and 70 years. The study was conducted at several fibromyalgia associations and specialized medical units. QoL was measured as the main outcome. In addition, functional capacity, muscular streng…

sj-jpg-2-cre-10.1177_02692155211022009 – Supplemental material for Effects of balance training on functionality, ankle instability, and dynamic balance outcomes in people with chronic ankle instability: Systematic review and meta-analysis

Supplemental material, sj-jpg-2-cre-10.1177_02692155211022009 for Effects of balance training on functionality, ankle instability, and dynamic balance outcomes in people with chronic ankle instability: Systematic review and meta-analysis by Sara Mollà-Casanova, Marta Inglés and Pilar Serra-Añó in Clinical Rehabilitation

sj-jpg-3-cre-10.1177_02692155211022009 – Supplemental material for Effects of balance training on functionality, ankle instability, and dynamic balance outcomes in people with chronic ankle instability: Systematic review and meta-analysis

Supplemental material, sj-jpg-3-cre-10.1177_02692155211022009 for Effects of balance training on functionality, ankle instability, and dynamic balance outcomes in people with chronic ankle instability: Systematic review and meta-analysis by Sara Mollà-Casanova, Marta Inglés and Pilar Serra-Añó in Clinical Rehabilitation