Experimental Models for Aging and their Potential for Novel Drug Discovery

An interesting area of scientific research is the development of potential antiaging drugs. In order to pursue this goal, it is necessary to gather the specific knowledge about the adequate preclinical models that are available to evaluate the beneficial effects of new potential drugs. This review is focused on invertebrate and vertebrate preclinical models used to evaluate the efficacy of antiaging compounds, with the objective to extend life span and health span. Research and online content related to aging, antiaging drugs, experimental aging models is reviewed. Moreover, in this review, the main experimental preclinical models of organisms that have contributed to the research in the pharmacol-ogy of lifespan extension and the understanding of the aging process are discussed. Dietary restriction (DR) constitutes a common experimental process to extend life span in all organisms. Besides, classical antiaging drugs such as resveratrol, rapamycin and metformin denominated as DR mimetics are also discussed. Likewise, the main therapeutic targets of these drugs include sirtuins, IGF-1, and mTOR, all of them being modulated by DR. Advances in molecular biology have uncovered the potential molecular pathways involved in the aging process. Due to their characteristics, invertebrate models are mainly used for drug screening. The National Institute on Aging (NIA) developed the Interventions Testing Program (ITP). At the pre-clinical level, the ITP uses Heterogeneous mouse model (HET) which is probably the most suitable rodent model to study potential drugs against aging prevention. The accelerated-senescence mouse P8 is also a mammalian rodent model for aging research. However, when evaluating the effect of drugs on a preclinical level, the evaluation must be done in non-human primates since it is the mammalian specie closest to humans. Research is needed to investigate the impact of new potential drugs for the increase of human quality o

Neuroprotective Effects of β-Caryophyllene against Dopaminergic Neuron Injury in a Murine Model of Parkinson's Disease Induced by MPTP

Parkinson's disease (PD) is one of the most common neurodegenerative disorders and is characterized by the loss of dopaminergic neurons in the substantia nigra (SN). Although the causes of PD are not understood, evidence suggests that its pathogenesis is associated with oxidative stress and inflammation. Recent studies have suggested a protective role of the cannabinoid signalling system in PD. β-caryophyllene (BCP) is a natural bicyclic sesquiterpene that is an agonist of the cannabinoid type 2 receptor (CB2R). Previous studies have suggested that BCP exerts prophylactic and/or curative effects against inflammatory bowel disease through its antioxidative and/or anti-inflammatory action. The present study describes the neuroprotective effects of BCP in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced murine model of PD, and we report the results of our investigation of its neuroprotective mechanism in neurons and glial cells. In the murine model, BCP pretreatment ameliorated motor dysfunction, protected against dopaminergic neuronal losses in the SN and striatum, and alleviated MPTP-induced glia activation. Additionally, BCP inhibited the levels of inflammatory cytokines in the nigrostriatal system. The observed neuroprotection and inhibited glia activation were reversed upon treatment with the CB2R selective antagonist AM630, confirming the involvement of the CB2R. These results indicate that BCP acts via multiple neuroprotective mechanisms in our murine model and suggest that BCP may be viewed as a potential treatment and/or preventative agent for PD

Ensheathing cell-conditioned medium directs the differentiation of human umbilical cord blood cells into aldynoglial phenotype cells

Despite their similarities to bone marrow precursor cells (PC), human umbilical cord blood (HUCB) PCs are more immature and, thus, they exhibit greater plasticity. This plasticity is evident by their ability to proliferate and spontaneously differentiate into almost any cell type, depending on their environment. Moreover, HUCB-PCs yield an accessible cell population that can be grown in culture and differentiated into glial, neuronal and other cell phenotypes. HUCB-PCs offer many potential therapeutic benefits, particularly in the area of neural replacement. We sought to induce the differentiation of HUCB-PCs into glial cells, known as aldynoglia. These cells can promote neuronal regeneration after lesion and they can be transplanted into areas affected by several pathologies, which represents an important therapeutic strategy to treat central nervous system damage. To induce differentiation to the aldynoglia phenotype, HUCB-PCs were exposed to different culture media. Mononuclear cells from HUCB were isolated and purified by identification of CD34 and CD133 antigens, and after 12 days in culture, differentiation of CD34? HUCB-PCs to an aldynoglia phenotypic, but not that of CD133? cells, was induced in ensheathing cell (EC)-conditioned medium. Thus, we demonstrate that the differentiation of HUCB-PCs into aldynoglia cells in EC-conditioned medium can provide a new source of aldynoglial cells for use in transplants to treat injuries or neurodegenerative diseases

Resveratrol: An Antiaging Drug with Potential Therapeutic Applications in Treating Diseases

pharmaceutical

Resveratrol: An Antiaging Drug with Potential Therapeutic Applications in Treating Diseases

The prevention of aging is one of the most fascinating areas in biomedicine. The first step in the development of effective drugs for aging prevention is a knowledge of the biochemical pathways responsible for the cellular aging process. In this context it seems clear that free radicals play a key role in the aging process. However, in recent years it has been demonstrated that the families of enzymes called sirtuins, specifically situin 1 (SIRT1), have an anti-aging action. Thus, the natural compound resveratrol is a natural compound that shows a very strong activation of SIRT1 and also shows antioxidant effects. By activating sirtuin 1, resveratrol modulates the activity of numerous proteins, including peroxisome proliferator-activated receptor coactivator-1α (PGC-1 alpha), the FOXO family, Akt (protein kinase B) and NFκβ. In the present review, we suggest that resveratrol may constitute a potential drug for prevention of ageing and for the treatment of several diseases due to its antioxidant properties and sirtuin activation

Resveratrol: An Antiaging Drug with Potential Therapeutic Applications in Treating Diseases

The prevention of aging is one of the most fascinating areas in biomedicine. The first step in the development of effective drugs for aging prevention is a knowledge of the biochemical pathways responsible for the cellular aging process. In this context it seems clear that free radicals play a key role in the aging process. However, in recent years it has been demonstrated that the families of enzymes called sirtuins, specifically situin 1 (SIRT1), have an anti-aging action. Thus, the natural compound resveratrol is a natural compound that shows a very strong activation of SIRT1 and also shows antioxidant effects. By activating sirtuin 1, resveratrol modulates the activity of numerous proteins, including peroxisome proliferator-activated receptor coactivator-1α (PGC-1 alpha), the FOXO family, Akt (protein kinase B) and NFκβ. In the present review, we suggest that resveratrol may constitute a potential drug for prevention of ageing and for the treatment of several diseases due to its antioxidant properties and sirtuin activation

Interactions Between Epilepsy and Plasticity

Undoubtedly, one of the most interesting topics in the field of neuroscience is the ability of the central nervous system to respond to different stimuli (normal or pathological) by modifying its structure and function, either transiently or permanently, by generating neural cells and new connections in a process known as neuroplasticity. According to the large amount of evidence reported in the literature, many stimuli, such as environmental pressures, changes in the internal dynamic steady state of the organism and even injuries or illnesses (e.g., epilepsy) may induce neuroplasticity. Epilepsy and neuroplasticity seem to be closely related, as the two processes could positively affect one another. Thus, in this review, we analysed some neuroplastic changes triggered in the hippocampus in response to seizure-induced neuronal damage and how these changes could lead to the establishment of temporal lobe epilepsy, the most common type of focal human epilepsy