X-Message-Number: 27888 From: "Hare, Tim R" <> Subject: RE: [CN] CR and brain aging Date: Mon, 1 May 2006 15:13:27 -0400 While a selection of recent literature wrt CR's impact on brain aging is compelling, what's arguably more important is avoiding the typical trend toward excess weight during mid-life, and eating nutritionally dense and variegated food. It's clear that even mild obesity is a risk factor for morbidity and mortality (more so in certain genotypes), and less clear what benefits such extremes as CR might afford a genetically diverse population of humans...especially if the practitioners aren't willing to monitor their biochemical response to (their version of) CR, and the scientific literature (where the typical clinician won't be of much use), aggressively. ------------------------------------- Random references from Pubmed.com query >> "(caloric or dietary) and restriction and aging and brain" Neuroprotective potential of dietary restriction against kainate-induced excitotoxicity in adult male Wistar rats. Brain Res Bull. 2005 Nov 30;67(6):482-91. Epub 2005 Aug 30. PMID: 16216697 [PubMed - indexed for MEDLINE] "The influence that dietary factors have on the nervous system and its susceptibility to disease, is an active area of biomedical research. Recent studies have shown that dietary restriction (DR) can have profound effect on brain function and vulnerability to injury and disease and can also enhance synaptic plasticity, which may increase the ability of brain to resist aging and restore function following injury." "The DR was observed to exert neuroprotection by enhancing the expression of HSP 70 in kainic acid treated rats." Life-long caloric restriction counteracts apoptotic effects of aging in the brain and bolsters the action of apoptosis inhibitors. Neurobiol Aging. 2005 Sep 26; [Epub ahead of print] PMID: 16198026 [PubMed - as supplied by publisher "Recent findings indicate that caloric restriction (CR) may have a profound effect on brain function and vulnerability to injury and diseases, by enhancing neuroprotection, stimulating the production of new neurons and increasing synaptic plasticity." "Caloric restriction may provide neuroprotection to the aging brain by partially suppressing the activation of caspase-3 and the cleavage of PARP, and by further up-regulating the specific caspase-3 inhibitor XIAP that may be involved in the increased resistance to apoptosis observed in CR animals." The Impact of Aging, Dietary Restriction, and Glucocorticoids on ApoE Gene Expression in Rat Brain. Ann N Y Acad Sci. 2005 Aug;1053:231-2. No abstract available. PMID: 16179527 [PubMed - in process] Macrosialin increases during normal brain aging are attenuated by caloric restriction. Neurosci Lett. 2005 Dec 23;390(2):76-80. PMID: 16157452 [PubMed - indexed for MEDLINE] "We show that macrosialin (CD68), a macrophage-specific protein, is increased by aging in selected brain regions of male C57BL/6NNia mice. In corpus callosum and striatum, macrosialin mRNA and protein increased >or=50% (24 months versus 4 months); hippocampus and cerebellum were unchanged. Caloric restriction (CR) attenuated these age-related increases." Caloric restriction prevents aging-associated changes in spike-mediated Ca2+ accumulation and the slow afterhyperpolarization in hippocampal CA1 pyramidal neurons. Neuroscience. 2005;135(2):413-20. PMID: 16112472 [PubMed - indexed for MEDLINE] Dietary restriction alters fine motor function in rats. Physiol Behav. 2005 Aug 7;85(5):581-92. PMID: 16045945 [PubMed - indexed for MEDLINE] Caloric restriction reduces cell loss and maintains estrogen receptor-alpha immunoreactivity in the pre-optic hypothalamus of female B6D2F1 mice. Neuro Endocrinol Lett. 2005 Jun;26(3):197-203. PMID: 15990721 [PubMed - indexed for MEDLINE] Dietary restriction at old age lowers mitochondrial oxygen radical production and leak at complex I and oxidative DNA damage in rat brain. J Bioenerg Biomembr. 2005 Apr;37(2):83-90. PMID: 15906153 [PubMed - indexed for MEDLINE] -----Original Message----- From: CryoNet F [mailto:] On Behalf Of Doug Skrecky Sent: Sunday, April 30, 2006 12:46 PM To: CryoNet F Subject: [CN] CR and brain aging [Considering the global effects of CR, one might be excused from assuming that this intervention would have far more dramatic effects on animal longevity than it does. A number of studies in adult animals have found no longevity advantage to CR at all. One possible explanation for these unexpected findings may be due to CR not affect the aging of the central nervous system. Since the energy supply of this tissue is preferentially preserved, caloric consumption by the brain can not be restricted due to simple dietary alterations. However if the functioning of the central nervous system is preserved by whatever means, then this might have a far more powerful effect on longevity through prolonged maintainance of the stem cell niche, via continued exposure to a youthful (brain-derived) hormonal environment. This might explain of the potent antiaging effect of chromium picolinate. The following abstract illustrates the lack of effect of CR on brain aging.] Ann N Y Acad Sci. 2004 Jun;1019:269-73. Measurement of the 4,834-bp mitochondrial DNA deletion level in aging rat liver and brain subjected or not to caloric restriction diet. Several studies have demonstrated an age-related accumulation of the amount of a specific 4834-bp mitochondrial DNA (mtDNA) deletion in different tissues of rat (liver, brain, and skeletal muscle). We investigated the influence of a caloric restriction diet (CR) on a selected age-associated marker of mtDNA damage, as the 4834-bp deletion, using quantitative real-time PCR. The mtDNA deleted level has been determined with respect to the mitochondrial D-loop level, using specific primers and TaqMan probes for each target. In liver we found an age-related increase of the deletion level (twofold) that was reversed and brought back to the adult level by a CR diet. On the contrary, in the brain the age-related increase of the deletion level (eightfold) was not affected by CR at all. The different effect of the CR on the deletion level in liver and brain might be a further element supporting the tissue-specificity of the aging process. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=27883 ############################################################# This message is sent to you because you are subscribed to the mailing list <>. 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