The role of Sirt1: At the crossroad between promotion of longevity and protection against Alzheimer's disease neuropathology

Wang, Jun; Fivecoat, Hayley C.; Ho, Lap; Pan, Yong; Ling, Emi; Pasinetti, Giulio Maria

doi:10.1016/j.bbapap.2009.11.015

Cited by 82 publications

(59 citation statements)

References 34 publications

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“…Similar effects of nutrient poor, calorically dense diets have been demonstrated in humans (Hodge, Dowse et al 1995;Tran, Komatsu et al 2001;Hursting, Lavigne et al 2003;Newby, Muller et al 2003). In humans, caloric restriction also retards aging and reduces rates of chronic disease; therefore, this simple measure may also help to reduce risk for neurodegeneration (Qin, Chachich et al 2006;Kim, Nguyen et al 2007;Wang, Fivecoat et al 2010). Beyond avoidance of excessive caloric intake, growing evidence suggests that the source of calories is also of concern.…”

Section: Western Diet and Insulin/igf Resistance Mediated Neurodegenementioning

confidence: 92%

Insulin Resistance, Cognitive Impairment and Neurodegeneration: Roles of Nitrosamine Exposure, Diet and Lifestyles

Monte¹,

Tong²,

Wands³

2011

Alzheimer's Disease Pathogenesis-Core Concepts, Shifting Paradigms and Therapeutic Targets

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Section: Western Diet and Insulin/igf Resistance Mediated Neurodegenementioning

confidence: 92%

Insulin Resistance, Cognitive Impairment and Neurodegeneration: Roles of Nitrosamine Exposure, Diet and Lifestyles

Monte¹,

Tong²,

Wands³

2011

Alzheimer's Disease Pathogenesis-Core Concepts, Shifting Paradigms and Therapeutic Targets

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“…These enzymes were found to play important roles in cellular signaling related to cell death, Ca 2+ homeostasis, and lifespan extension, and their activities are highly dependent on the level of NAD + available in the cell (4,5,8,9,33,41,42). In this study, other than the decreases in the intracellular NAD + level and RX (or RP), we also observed a slower decline of the total intracellular NAD content in the human brain during healthy aging, which collectively reflects reduced NAD + availability in the aged brain.…”

Section: Discussionmentioning

confidence: 99%

In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences

Zhu

Lü

Lee

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

372

347

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NAD is an essential metabolite that exists in NAD + or NADH form in all living cells. Despite its critical roles in regulating mitochondrial energy production through the NAD + /NADH redox state and modulating cellular signaling processes through the activity of the NAD + -dependent enzymes, the method for quantifying intracellular NAD contents and redox state is limited to a few in vitro or ex vivo assays, which are not suitable for studying a living brain or organ. Here, we present a magnetic resonance (MR) -based in vivo NAD assay that uses the high-field MR scanner and is capable of noninvasively assessing NAD + and NADH contents and the NAD + /NADH redox state in intact human brain. The results of this study provide the first insight, to our knowledge, into the cellular NAD concentrations and redox state in the brains of healthy volunteers. Furthermore, an age-dependent increase of intracellular NADH and age-dependent reductions in NAD + , total NAD contents, and NAD + /NADH redox potential of the healthy human brain were revealed in this study. The overall findings not only provide direct evidence of declined mitochondrial functions and altered NAD homeostasis that accompany the normal aging process but also, elucidate the merits and potentials of this new NAD assay for noninvasively studying the intracellular NAD metabolism and redox state in normal and diseased human brain or other organs in situ.redox state | NAD | in vivo 31 P MR spectroscopy | human brain | aging N AD, a multifunctional metabolite found in all living cells, has been the interest of many scientific investigations since its discovery in the early 20th century (1). NAD is known to convert between its oxidized NAD + and reduced NADH forms during the breakdown of nutrients; hence, the intracellular NAD + /NADH redox state reflects the metabolic balance of the cell in generating ATP energy through oxidative phosphorylation in mitochondria and/or glycolysis in cytosol (2). More recently, after several protein families associated with cell survival were found to use NAD + as their main substrate with activities also regulated by the availability of the NAD + , the full extent of the NAD's function as a metabolic regulator began to unfold (3-5). A growing number of studies have indicated that NAD + can modulate metabolic signaling pathways and mediate important cellular processes, including calcium homeostasis, gene expression, aging, degeneration, and cell death; therefore, the cellular NAD could serve as a therapeutic target for treating various metabolic or age-related diseases and promoting longevity (6-12).Despite the critical relevance of the intracellular NAD metabolism to human health and diseases, assessment of NAD contents and NAD + /NADH redox state is extremely challenging. Only a few invasive techniques based on biochemical assays or autofluorescence methods have been used to analyze tissue samples or cell extracts (13,14). However, during the preparation of such ex vivo sample, the NAD + and NADH contents are likely altered, beca...

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“…The targets of SIRT1, which is by far the best characterized sirtuin, include histones, a broad range of stress signalling proteins, and transcription factors (TFs) ( Table I). SIRT1 is mainly involved in the regulation of the stress response and macromolecular repair (through its influence on p53 [64], heat shock factor HSF1 [114], forkhead box subgroup O -FOXO proteins [25], peroxisome proliferator-activated receptor -PPAR family [159], Ku70 [85]), anti-inflammatory response (via NF-κB [136,230]), exerts a pro-survival influence (through IIS -insulin/ IGF-I signalling [210]), and modulates the generation of mitochondria [66]. Long-term experimental SIRT1 activation in vivo is able to retard the onset of agerelated metabolic stress and mortality [136].…”

Section: Introductionmentioning

confidence: 99%

Sirtuins and their interactions with transcription factors and poly(ADP-ribose) polymerases

Jęśko¹,

Strosznajder²

2016

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A b s t r a c tSirtuins vast number of targets in many cellular compartments, and some display additional enzymatic activities including mono(ADP-ribosyl)ation. SIRTs interact with multiple signalling proteins, transcription factors and enzymes including p53, FOXOs (forkhead box subgroup O), PPARs (peroxisome proliferator-activated receptors), NF-κB, and DNA-PK (DNA-dependent protein kinase). Sirtuins also interact extensively with the family of poly(ADPribose) polymerases (PARPs), a crucial and widespread class of NAD

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The role of Sirt1: At the crossroad between promotion of longevity and protection against Alzheimer's disease neuropathology

Cited by 82 publications

References 34 publications

Insulin Resistance, Cognitive Impairment and Neurodegeneration: Roles of Nitrosamine Exposure, Diet and Lifestyles

Insulin Resistance, Cognitive Impairment and Neurodegeneration: Roles of Nitrosamine Exposure, Diet and Lifestyles

In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences

Sirtuins and their interactions with transcription factors and poly(ADP-ribose) polymerases

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