Article

Calorie restriction attenuates Alzheimer's disease type brain amyloidosis in Squirrel monkeys (Saimiri sciureus)

Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA.
Journal of Alzheimer's disease: JAD (Impact Factor: 4.15). 01/2007; 10(4):417-22.
Source: PubMed

ABSTRACT

Recent studies from our laboratories and others suggest that calorie restriction (CR) may benefit Alzheimer's disease (AD) by preventing amyloid-beta (Abeta) neuropathology in the mouse models of AD. Moreover, we found that promotion of the NAD+-dependent SIRT1 mediated deacetylase activity, a key regulator in CR extension of life span, may be a mechanism by which CR influences AD-type neuropathology. In this study we continued to explore the role of CR in AD-type brain amyloidosis in Squirrel monkeys (Saimiri sciureus). Monkeys were maintained on the normal and CR diets throughout the entire lifespan until they died of natural causes. We found that 30% CR resulted in reduced contents of Abeta1-40 and Abeta1-42 peptides in the temporal cortex of Squirrel monkeys, relative to control (CON) fed monkeys. The decreased contents of cortical Abeta peptide inversely correlated with SIRT1 protein concentrations in the same brain region; no detectable change in total full-length amyloid-beta protein precursor (AbetaPP) level was found. Most interestingly, we found that 30% CR resulted in a select elevation of alpha- but not beta- or gamma- secretase activity which coincided with decreased ROCK1 protein content in the same brain region, relative to CON group. Collectively, the study suggests that investigation of the role of CR in non-human primates may provide a valuable approach for further clarifying the role of CR in AD.

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    • "A most recent study has shown that caloric restriction significantly increases lifespan of calanoid copepod Paracartia grani (Saiz et al., 2015). Besides its beneficial effects on lifespan, it has been shown in several models that CR has positive effects on age-related conditions such as reduction in Alzheimer's disease-type amyloidneuropathology (Patel et al., 2005; Qin et al., 2006 ), risk of cardiovascular disease and diabetes (Lane et al., 1999), and cancer formation (Colman et al., 2009). Inhibition of TOR by rapamycin increased lifespan in a wide range of taxa (Table 2). "
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    ABSTRACT: Ageing is the organisms increased susceptibility to death, which is linked to accumulated damage in the cells and tissues. Ageing is a complex process regulated by crosstalk of various pathways in the cells. Ageing is highly regulated by the Target of Rapamycin (TOR) pathway activity. TOR is an evolutionary conserved key protein kinase in the TOR pathway that regulates growth, proliferation and cell metabolism in response to nutrients, growth factors and stress. Comparing the ageing process in invertebrate model organisms with relatively short lifespan with mammals provides valuable information about the molecular mechanisms underlying the ageing process faster than mammal systems. Inhibition of the TOR pathway activity via either genetic manipulation or rapamycin increases lifespan profoundly in most invertebrate model organisms. This contribution will review the recent findings in invertebrates concerning the TOR pathway and effects of TOR inhibition by rapamycin on lifespan. Besides some contradictory results, the majority points out that rapamycin induces longevity. This suggests that administration of rapamycin in invertebrates is a promising tool for pursuing the scientific puzzle of lifespan prolongation.
    No preview · Article · Jan 2016 · Mechanisms of Ageing and Development
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    • "In support of this, CR studies in AD-type brain amyloidosis in Squirrel monkeys were similarly found to result in reduced Aβ. Importantly, CR and reduced Aβ are correlated with increased SIRT1 levels in both in monkeys and mice [93, 134]. CR mediated SIRT1 expression appears to reduce Aβ peptide generation through mechanisms that favor a α-secretase non-amyloidogenic processing of APP. "
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    ABSTRACT: Sirtuins are a conserved family of deacetylases whose activities are dependent on nicotinamide adenine dinucleotide (NAD+). Sirtuins act in different cellular compartments, such as the nucleus where they deacetylate histones and transcriptional factors, in the cytoplasm where they modulate cytoskeletal and signaling molecules, and in the mitochondria where they engage components of the metabolic machinery. Collectively, they tune metabolic processes to energy availability, and modulate stress responses, protein aggregation, inflammatory processes, and genome stability. As such, they have garnered much interest and have been widely studied in aging and age-related neurodegeneration. In this chapter, we review the identification of sirtuins and their biological targets. We focus on their biological mechanisms of action and how they might be regulated, including via NAD metabolism, transcriptional and posttranscriptional control, and as targets of pharmacological agents. Lastly, we highlight the numerous studies suggesting that sirtuins are efficacious therapeutic targets in neurodegenerative disease and injury. Electronic supplementary material The online version of this article (doi:10.1007/s13311-013-0214-5) contains supplementary material, which is available to authorized users.
    Preview · Article · Sep 2013 · Journal of the American Society for Experimental NeuroTherapeutics
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    • "Moderate reduction in calorie intake in the absence of malnutrition has been recently demonstrated to help prevent or delay AD [34] [35]. In addition, it has been demonstrated that CR ameliorates A␤ and tau pathology and improves cognitive performance in AD mouse models [36] [37] [38] [39] [40] [41]. Although the exact mechanism by which CR influences AD remains unclear, there are at least a few identified pathways that involve neurogenesis. "
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    ABSTRACT: Alterations in hippocampal neurogenesis have been recognized as an integral part of Alzheimer's disease. Adult hippocampal neurogenesis is regulated by intrinsic and extrinsic factors; one of them is diet. This review provides an assessment of the current state of the field in hippocampal neurogenesis studies in Alzheimer's disease and focuses on the role of diet. The review highlights some of the key dietary compounds and interventions such as calorie restriction, fat, polyphenols, zinc, folate, alcohol and thiamine, and emphasizes the pathways that they modify.
    Full-text · Article · Aug 2013 · Journal of Alzheimer's disease: JAD
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