Instituto Nacional Of Geriatria
Instituto Nacional Of Geriatria
Colin-Gonzalez A.L.,Instituto Nacional Of Neurologia Y Neurocirugia |
Luna-Lopez A.,Instituto Nacional Of Geriatria |
Konigsberg M.,Metropolitan Autonomous University |
Ali S.F.,National Center for Toxicological Research (NCTR) |
And 2 more authors.
Neuroscience | Year: 2014
Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a transcription factor involved in the orchestration of antioxidant responses. Although its pharmacological activation has been largely hypothesized as a promising tool to ameliorate the progression of neurodegenerative events, the actual knowledge about its modulation in neurotoxic paradigms remains scarce. In this study, we investigated the early profile of Nrf2 modulation in striatal slices of rodents incubated in the presence of the toxic kynurenine pathway metabolite, quinolinic acid (QUIN). Tissue slices from rats and mice were obtained and used throughout the experiments in order to compare inter-species responses. Nuclear Nrf2 protein levels and oxidative damage to lipids were compared. Time- and concentration-response curves of all markers were explored. Nrf2 nuclear activation was corroborated through phase 2 antioxidant protein expression. The effects of QUIN on Nrf2 modulation and oxidative stress were also compared between slices of wild-type (Nrf2+/+) and Nrf2 knock-out (Nrf2-/-) mice. The possible involvement of the N-methyl-d-aspartate receptor (NMDAr) in the Nrf2 modulation and lipid peroxidation was further explored in mice striatal slices. In rat striatal slices, QUIN stimulated the Nrf2 nuclear translocation. This effect was accompanied by augmented lipid peroxidation. In the mouse striatum, QUIN per se exerted an induction of Nrf2 factor only at 1h of incubation, and a concentration-response effect on lipid peroxidation after 3h of incubation. QUIN stimulated the striatal content of phase 2 enzymes. Nrf2-/- mice were slightly more responsive than Nrf2+/+ mice to the QUIN-induced oxidative damage, and completely unresponsive to the NMDAr antagonist MK-801 when tested against QUIN. Findings of this study indicate that: (1) Nrf2 is modulated in rodent striatal tissue in response to QUIN; (2) Nrf2-/- striatal tissue was moderately more vulnerable to oxidative damage than the Wt condition; and (3) early Nrf2 up-regulation reflects a compensatory response to the QUIN-induced oxidative stress in course as part of a general defense system, whereas Nrf2 down-regulation might contribute to more intense oxidative cell damage. © 2013 IBRO.
Lourenco R.A.,State University of Rio de Janeiro |
Perez-zepeda M.,Instituto Nacional Of Geriatria |
Gutierrez-robledo L.,National Institute of Geriatrics |
Garcia-garcia F.J.,Complejo Hospitalario Of Toledo |
Rodriguez manas L.,Hospital Universitario Of Getafe
Age and Ageing | Year: 2015
Background: there is a lack of consensus on the diagnosis of sarcopenia. A screening and diagnostic algorithm was proposed by the European Working Group on Sarcopenia in Older People (EWGSOP).Objective: to assess the performance of the EWGSOP algorithm in determining the proportion of subjects suspected of having sarcopenia and selected to undergo subsequent muscle mass (MM) measurement.Design: a cross-sectional study.Setting: the cohorts, Frailty in Brazilian Older People Study-Rio de Janeiro (FIBRA-RJ), Brazil; Coyoacan Cohort (CC), Mexico City, Mexico; and Toledo Study for Healthy Aging (TSHA), Toledo, Spain.Subjects: three thousand two hundred and sixty community-dwelling individuals, 65 years and older.Methods: initially, the EWGSOP algorithm was applied using its originally proposed cut-off values for gait speed and handgrip strength; in the second step, values tailored for the specific cohorts were used.Results: using the originally suggested EWGSOP cut-off points, 83.4% of the total cohort (94.4% in TSHA, 75.5% in FIBRA-RJ, 67.8% in CC) would have been considered as suspected of sarcopenia. Adapted cut-off values lowered the proportion of abnormal results to 34.2% (quintile-based approach) and 23.71% (z-score approach).Conclusions: the algorithm proposed by the EWGSOP is of limited clinical utility in screening older adults for sarcopenia due to the high proportion of subjects selected to further undergo MM assessment. Tailoring cut-off values to specific characteristics of the population being studied reduces the number of people selected for MM assessment, probably improving the performance of the algorithm. Further research including the objective measure of MM is needed to determine the accuracy of these specific cut-off points. © The Author 2014.
Andrade F.C.D.,University of Illinois at Urbana - Champaign |
Lopez-Ortega M.,Instituto Nacional Of Geriatria
Journal of Aging and Health | Year: 2017
Objective: This study examines educational differences in health conditions among middle-aged and older adults in Brazil and Mexico. Method: Cross-sectional data from the 2013 Brazilian National Health Survey and the 2012 Mexican National Health and Nutrition Survey were used in the analyses. We used multivariate Poisson regressions to examine the relationship between educational level and prevalence of common health conditions (obesity, abdominal obesity, diabetes, hypertension, heart disease, and hearing and visual impairments). Results: Socioeconomic and sex inequalities persist in both countries. In general, low levels of education were associated with higher risk for having health conditions. However, men of lower education had a smaller risk of abdominal obesity and hypertension. Discussion: Brazil and Mexico have expanded public health actions aimed at improving health behaviors, diagnosis, and access to treatment of chronic conditions. However, important social disparities remain. Improving lifestyle behaviors, such as physical activity and dietary habits, could benefit both countries. © The Author(s) 2017.
Michan S.,Instituto Nacional Of Geriatria
Current Pharmaceutical Design | Year: 2013
Our understanding of the magnitude and physiological significance of proteome lysine acetylation remained incipient for five decades since it was first described. State-of-the-art methodologies, ranging from functional genomics to large-scale proteomics, have recently uncovered that this modification is more broadly represented in proteins than previously recognized, thus constituting the “acety-lome.” At present, it is estimated that acetylome covers only one tenth of the proteome, however, due its potential significance in physiology is capturing great attention. The first components of the cellular machinery, which finely orchestrate acetylome homeostasis, were identified by the end of last century. Since then, the majority of our growing knowledge concerning the physiological relevance of proteome reversible acetylation comes from the study of sirtuins, a unique type of lysine deacetylase that uses NAD+. Sirtuins participate in a variety of cellular processes, ranging from transcription, DNA repair, energy balance, mitochondrial biogenesis and cell division, to apoptosis, autophagy and aging. Within the brain, besides their widespread epigenetic effects of dynamically modifying histones, sirtuins also target a variety of non-histone proteins either commonly deregulated in pathologies, or that participate in normal cerebral functions. For example, they modulate critical elements of the circadian rhythms, neurogenesis, synapses, cognition, serotonin synthesis, myelina-tion, and proteins involved in neuropathology. Acetylome dynamics, and its regulation by sirtuins, may also help to better understand the molecular mechanisms underlying brain aging. This work reviews the pathways as orchestrated by the interplay between acetylome and sirtuins in the brain, from physiology involvement, to aging processes, and pathological settings. © 2013 Bentham Science Publishers
North B.J.,Harvard University |
Rosenberg M.A.,Beth Israel Deaconess Medical Center |
Jeganathan K.B.,Rochester College |
Hafner A.V.,Harvard University |
And 11 more authors.
EMBO Journal | Year: 2014
Mice overexpressing the mitotic checkpoint kinase gene BubR1 live longer, whereas mice hypomorphic for BubR1 (BubR1H/H) live shorter and show signs of accelerated aging. As wild-type mice age, BubR1 levels decline in many tissues, a process that is proposed to underlie normal aging and age-related diseases. Understanding why BubR1 declines with age and how to slow this process is therefore of considerable interest. The sirtuins (SIRT1-7) are a family of NAD+-dependent deacetylases that can delay age-related diseases. Here, we show that the loss of BubR1 levels with age is due to a decline in NAD+ and the ability of SIRT2 to maintain lysine-668 of BubR1 in a deacetylated state, which is counteracted by the acetyltransferase CBP. Overexpression of SIRT2 or treatment of mice with the NAD+ precursor nicotinamide mononucleotide (NMN) increases BubR1 abundance in vivo. Overexpression of SIRT2 in BubR1H/H animals increases median lifespan, with a greater effect in male mice. Together, these data indicate that further exploration of the potential of SIRT2 and NAD+ to delay diseases of aging in mammals is warranted. © 2014 The Authors.
Luna-Lopez A.,Instituto Nacional Of Geriatria |
Gonzalez-Puertos V.Y.,Metropolitan Autonomous University |
Lopez-Diazguerrero N.E.,Metropolitan Autonomous University |
Konigsberg M.,Metropolitan Autonomous University
Journal of Cell Communication and Signaling | Year: 2014
Last, we discuss mild oxidative stress in association to low-grade chronic inflammation as a stimulating avenue to be explored and the unexpected effects proposed by the obesity paradox theory. All the previous might help to clarify the reasons why centenarians are able to reach the extreme limits of human life span, which could probably be related to the way they deal with homeostasis maintenance, providing an opportunity for hormesis to intervene significantly.In order to survive living organisms have developed multiple mechanisms to deal with tough environmental conditions. Hormesis is defined as a process in which exposure to a low dose of a chemical agent or environmental factor that is damaging at higher doses induces an adaptive beneficial effect on the cell or organism. In this paper, we examine several ideas that might be taken into consideration before using hormesis as a therapeutic tool to improve health and life span, and hopefully will open the discussion for new and interesting debates regard hormesis. The first one is to understand that the same stressor or inductor can activate different pathways in a parallel or dual response, which might lead to diverse outcomes. Another idea is related to the mechanisms involved in activating Nrf2, which might be different and have diverse hormetic effects. © 2014, The International CCN Society.
Botero M.A.,Instituto Nacional Of Geriatria
Cadernos de Saude Publica | Year: 2014
The objective of this study was to calculate average years of life lost due to breast and cervical cancer in Mexico in 2000 and 2010. Data on mortality in women aged between 20 and 84 years was obtained from the National Institute for Statistics and Geography. Age-specific mortality rates and average years of life lost, which is an estimate of the number of years that a person would have lived if he or she had not died prematurely, were estimated for both diseases. Data was disaggregated into five-year age groups and socioeconomic status based on the 2010 marginalization index obtained from the National Population Council. A decrease in average years of life lost due to cervical cancer (37.4%) and an increase in average years of life lost due breast cancer (8.9%) was observed during the period studied. Average years of life lost due to cervical cancer was greater among women living in areas with a high marginalization index, while average years of life lost due to breast cancer was greater in women from areas with a low marginalization index.
Michan S.,Instituto Nacional Of Geriatria
Frontiers in Bioscience - Landmark | Year: 2014
Among diverse environmental factors that modify aging, diet has a profound effect. Calorie restriction (CR), which entails reduced calorie consumption without malnutrition, is the only natural regimen shown to extend maximum and mean lifespan, as well as healthspan in a wide range of organisms. Although the knowledge about the biological mechanisms underlying CR is still incipient, various approaches in biogerontology research suggest that CR can ameliorate hallmarks of aging at the cellular level including telomere erosion, epigenetic alterations, stem cells depletion, cellular senescence, mitochondrial dysfunction, genomic instability, proteostasis imbalance, impaired nutrient sensing and abnormal intercellular communication. Currently, the NAD +/sirtuin pathway is one of the few mechanisms described to mediate CR effects and sirtuin-activating compounds (STACs) mimic many effects of CR. Herein, we discuss the effects of CR on healthspan with emphasis on neuroprotection, how CR counteracts cellular aging, how sirtuin pathways intertwine with CR, and the relevance of STACs in mimicking CR effects.
Gutierrez-Robledo L.M.,Instituto Nacional Of Geriatria |
Arrieta-Cruz I.,Instituto Nacional Of Geriatria
Gaceta Medica de Mexico | Year: 2015
Dementia is one of the facts than most contributes to the disability and dependence in elderly people. Alzheimer´s disease is the cause more common of dementia in the world. In Mexico, the prevalence of Alzheimer´s disease is 7.3% and incidence of 27.3 per 1,000 people/year. Mexican population studies have determined that Alzheimer´s disease is highly associated to women and their risk to develop it is increased with metabolic syndrome, cardiovascular disease, or depression. The projections are that there will be 3.5 million elderly people affected by Alzheimer´s disease by 2050 in Mexico; this will have a major impact on the healthcare system. The National Institute of Geriatrics from Mexico’s Ministry of Health has released a first proposal for a National Alzheimer and Other Dementias’ Plan. The central aim of this plan is to promote the well being of people affected by Alzheimer´s disease and their families through of the strengthening of the Mexican healthcare system and the support of other responsible institutions. © 2015, Academia Nacional de Medicina. All rights reserved.
Fossion R.,Instituto Nacional Of Geriatria |
Fossion R.,National University of Costa Rica
AIP Conference Proceedings | Year: 2014
This contribution discusses some recent applications of time-series analysis in Random Matrix Theory (RMT), and applications of RMT in the statistial analysis of eigenspectra of correlation matrices of multivariate time series. © 2014 AIP Publishing LLC.