SIRT1 Deficiency in Microglia Contributes to Cognitive Decline in Aging and Neurodegeneration via Epigenetic Regulation of IL-1β

Tarragó

Molecular and Cellular Endocrinology

2017

158

188

Life as we know it cannot exist without the nucleotide nicotinamide adenine dinucleotide (NAD). From the simplest organism, such as bacteria, to the most complex multicellular organisms, NAD is a key cellular component. NAD is extremely abundant in most living cells and has traditionally been described to be a cofactor in electron transfer during oxidation-reduction reactions. In addition to participating in these reactions, NAD has also been shown to play a key role in cell signaling, regulating several pathways from intracellular calcium transients to the epigenetic status of chromatin. Thus, NAD is a molecule that provides an important link between signaling and metabolism, and serves as a key molecule in cellular metabolic sensoring pathways. Importantly, it has now been clearly demonstrated that cellular NAD levels decline during chronological aging. This decline appears to play a crucial role in the development of metabolic dysfunction and age-related diseases. In this review we will discuss the molecular mechanisms responsible for the decrease in NAD levels during aging. Since other reviews on this subject have been recently published, we will concentrate on presenting a critical appraisal of the current status of the literature and will highlight some controversial topics in the field. In particular, we will discuss the potential role of the NADase CD38 as a driver of age-related NAD decline.

Section: What Causes the Nad Decline Observed During The Aging Process?mentioning

confidence: 99%

NAD and the aging process: Role in life, death and everything in between

Tarragó

Molecular and Cellular Endocrinology

2017

158

188

Appl. Physiol. Nutr. Metab.

“…Chronic inflammation is involved in the pathophysiology of many neurodegenerative conditions (Cho et al 2015). Related to the genesis and worsening of these is the increased blood-brain barrier (BBB) permeability, an endothelial structure which controls the influx and efflux of components between blood flow and central nervous system (CNS) (Abbott 2000).…”

Section: Introductionmentioning

confidence: 99%

Exercise and taurine in inflammation, cognition, and peripheral markers of blood-brain barrier integrity in older women

Chupel

Minuzzi

Furtado

et al. 2018

1Exercise and taurine in inflammation, cognition, and peripheral markers of blood-brain barrier integrity in older women Authors:Matheus Abstract:Immunosenescence contribute to increase the blood-brain barrier (BBB) permeability, leading cognitive impairment and neurodegeneration. Thus, we investigated the anti-inflammatory effect of exercise and taurine supplementation on peripheral markers of blood-brain barrier, inflammation, and cognition of elderly women. Forty-eight elderly women (83.58±6.9 years) participated in the study, and were allocated into combined exercise training (CET: n=13), taurine supplementation (TAU: n=12), exercise training associated with taurine (CET+TAU: n=11), or control group (CG: n=12). Exercise was applied twice a week (multi-modal exercise). Taurine ingestion was 1.5g., once a day. Participants were evaluated before and after 14-weeks of intervention. Plasma levels of IL-1β, IL-1ra, IL-6, IL-10, IL-17, TNF-α, and serum concentration of S100β and neuron specific enolase (NSE) were determined. The mini mental state examination (MMSE) was also applied.Concentrations of S100β were maintained in all intervention groups, while a subtle increase in the CG was found. NSE levels increased only in TAU group (p<0.05). CET reduced TNF-α, IL-6, and IL-1β/IL-1ra, IL-6/IL10, TNF-α/IL-10 ratios (p<0.05). TAU decreased the IL-1β/IL-1ra ratio (p<0.05). MMSE score increased only in CET+TAU group (p<0.05). Multiple regression analysisshowed that there was a trend for changes in IL-1β and CCI to be independently associated with changes in S100β. Exercise and taurine decreased inflammation, and maintained the BBB integrity in elderly women. Exercise emerged as an important tool to improve brain health even when started at advanced ages.

“…While rodents and humans share a great deal of similarity in the organization of the immune system (Haley, 2003;Bailey et al, 2013;Cho et al, 2015;Plackett et al, 2003;Gelinas and McLaurin, 2005;Ferrari et al, 2001), a growing body of literature suggests that immune systems of rodents and humans differ in ways that significantly hamper translation of results obtained in preclinical trials in rodents to successful therapeutics in humans (Renshaw et al, 2002;Boehmer et al, 2004;Rhoades and Orne, 1998;Swift et al, 2001;Rammos et al, 2014;Wang et al, 2014;Bruhns, 2012;Rousseaux et al, 1983;Mestas and Hughes, 2004). Rodents and humans respond differently to infectious agents and possess disparate inflammatory responses (Leist and Hartung, 2013;Tuomela and Lahesmaa, 2013).…”

Section: Immunological Considerations: Disparities Between Rodents Anmentioning

confidence: 99%

Advantages of nonhuman primates as preclinical models for evaluating stem cell-based therapies for Parkinson's disease

Grow¹,

McCarrey²,

Navara³

2016

Stem Cell Research

The derivation of dopaminergic neurons from induced pluripotent stem cells brings new hope for a patient-specific, stem cell-based replacement therapy to treat Parkinson's disease (PD) and related neurodegenerative diseases; and this novel cell-based approach has already proven effective in animal models. However, there are several aspects of this procedure that have yet to be optimized to the extent required for translation to an optimal cell-based transplantation protocol in humans. These challenges include pinpointing the optimal graft location, appropriately scaling up the graft volume, and minimizing the risk of chronic immune rejection, among others. To advance this procedure to the clinic, it is imperative that a model that accurately and fully recapitulates characteristics most pertinent to a cell-based transplantation to the human brain is used to optimize key technical aspects of the procedure. Nonhuman primates mimic humans in multiple ways including similarities in genomics, neuroanatomy, neurophysiology, immunogenetics, and age-related changes in immune function. These characteristics are critical to the establishment of a relevant model in which to conduct preclinical studies to optimize the efficacy and safety of cell-based therapeutic approaches to the treatment of PD. Here we review previous studies in rodent models, and emphasize additional advantages afforded by nonhuman primate models in general, and the baboon model in particular, for preclinical optimization of cell-based therapeutic approaches to the treatment of PD and other neurodegenerative diseases. We outline current unresolved challenges to the successful application of stem cell therapies in humans and propose that the baboon model in particular affords a number of traits that render it most useful for preclinical studies designed to overcome these challenges.