Calorie restriction attenuates Alzheimer's disease type brain amyloidosis in Squirrel monkeys (Saimiri sciureus).
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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ABSTRACT: The silent mating type information regulation 2 proteins (sirtuins) 1 of class III histone deacetylases (HDACs) have been associated with health span and longevity. SIRT1, the best studied member of the mammalian sirtuins, has a myriad of roles in multiple tissues and organs. However, a significant part of SIRT1's role that impinges on aging and lifespan may lie in its activities in the central nervous system (CNS) neurons. Systemically, SIRT1 influences energy metabolism and circadian rhythm through its activity in the hypothalamic nuclei. From a cell biological perspective, SIRT1 is a crucial component of multiple interconnected regulatory networks that modulate dendritic and axonal growth, as well as survival against stress. This neuronal cell autonomous activity of SIRT1 is also important for neuronal plasticity, cognitive functions, as well as protection against aging-associated neuronal degeneration and cognitive decline. We discuss recent findings that have shed light on the various activities of SIRT1 in the brain, which collectively impinge on aging-associated disorders and lifespan.Frontiers in Cellular Neuroscience 01/2015; 9:64. DOI:10.3389/fncel.2015.00064 · 4.18 Impact Factor
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ABSTRACT: Alzheimer's disease (AD) is a devastating disorder that strikes 1 in 10 Americans over the age of 65, and almost half of all Americans over 85years old. The odds of an individual developing Alzheimer's disease double every five years after the age of 65. While it has become increasingly common to meet heart attack or cancer survivors, there are no Alzheimer's disease survivors. There is mounting evidence that dietary polyphenols, including resveratrol, may beneficially influence Alzheimer's disease (AD). Based on this consideration, several studies reported in the last few years were designed to validate sensitive and reliable translational tools to mechanistically characterize brain bioavailable polyphenols as disease-modifying agents to help prevent the onset of AD dementia and other neurodegenerative disorders. Several research groups worldwide with expertise in AD, plant biology, nutritional sciences, and botanical sciences have reported very high quality studies that ultimately provided the necessary information showing that polyphenols and their metabolites, which come from several dietary sources, including grapes, cocoa etc., are capable of preventing AD. The ultimate goal of these studies was to provide novel strategies to prevent the disease even before the onset of clinical symptoms. The studies discussed in this review article provide support that the information gathered in the last few years of research will have a major impact on AD prevention by providing vital knowledge on the protective roles of polyphenols, including resveratrol.Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 10/2014; 1852(6). DOI:10.1016/j.bbadis.2014.10.006 · 5.09 Impact Factor
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ABSTRACT: Memory consolidation is the process by which relevant information is selected and transferred from a short-term, fragile state, into a stable, longer term domain from which it can be recalled. Effective memory underpins our ability to carry out everyday activities. When memory consolidation fails, such as in Alzheimer's disease, the consequences can be devastating. Understanding the neurobiology of memory will help develop treatments for patients with memory loss. Here we describe the myriad processes involved in memory consolidation, including cholinergic and dopaminergic neurotransmission predominantly in hippocampal networks. We discuss established therapies as well as potential novel strategies for boosting cognition. Future approaches to enhancement of memory consolidation include not only pharmacological and neurosurgical treatments, but also lifestyle interventions - for example, modifications to sleep, exercise and diet.Translational Neuroscience 12/2013; 4(4). DOI:10.2478/s13380-013-0140-3 · 0.72 Impact Factor