4 replies to this topic

[Hedgehog]

Abstract

Deregulation of mitochondrial function is a common feature in multiple aspects of aging. In addition to playing a role in aging-associated disease, decline in mitochondrial energy metabolism is likely to be important in the development of metabolic disease. Furthermore, altered mitochondrial function is a conserved feature in caloric restriction — a dietary intervention that delays aging in diverse species. The transcriptional co-activator PGC-1α is a critical regulator of mitochondrial energy metabolism and biogenesis. PGC-1α is uniquely poised as a potential target for correcting the effects of age on mitochondrial decline. We describe the cellular and tissue specific mechanisms of PGC-1α regulation and illustrate how these pathways may be involved in the aging process

http://www.ncbi.nlm....pubmed/19371772

See section 6

6. Pharmacological anti-aging strategies: resveratrol


For those are science minded might be interested in this...

To Forum Admin. I wasn't sure if this should go in the Resveratrol or bioscience section.

Attached Files

•  PGC_1aplha.pdf   520.85KB   102 downloads

[DeadMeat]

Perhaps lithium would be an interesting PGC-1alpha upregulator.
http://www.ncbi.nlm....pubmed/17451429

Lithium increases PGC-1alpha expression and mitochondrial biogenesis in primary bovine aortic endothelial cells.
Struewing IT, Barnett CD, Tang T, Mao CD.
Graduate Center for Nutritional Sciences, University of Kentucky, 900 Limestone Street, Lexington, KY 40536, USA.

Lithium is a therapeutic agent commonly used to treat bipolar disorder and its beneficial effects are thought to be due to a combination of activation of the Wnt/beta-catenin pathway via inhibition of glycogen synthase kinase-3beta and depletion of the inositol pool via inhibition of the inositol monophosphatase-1. We demonstrated that lithium in primary endothelial cells induced an increase in mitochondrial mass leading to an increase in ATP production without any significant change in mitochondrial efficiency. This increase in mitochondrial mass was associated with an increase in the mRNA levels of mitochondrial biogenesis transcription factors: nuclear respiratory factor-1 and -2beta, as well as mitochondrial transcription factors A and B2, which lead to the coordinated upregulation of oxidative phosphorylation components encoded by either the nuclear or mitochondrial genome. These effects of lithium on mitochondrial biogenesis were independent of the inhibition of glycogen synthase kinase-3beta and independent of inositol depletion. Also, expression of the coactivator PGC-1alpha was increased, whereas expression of the coactivator PRC was not affected. Lithium treatment rapidly induced a decrease in activating Akt-Ser473 phosphorylation and inhibitory Forkhead box class O (FOXO1)-Thr24 phosphorylation, as well as an increase in activating c-AMP responsive element binding (CREB)-Ser133 phosphorylation, two mechanisms known to control PGC-1alpha expression. Together, our results show that lithium induces mitochondrial biogenesis via CREB/PGC-1alpha and FOXO1/PGC-1alpha cascades, which highlight the pleiotropic effects of lithium and reveal also novel beneficial effects via preservation of mitochondrial functions.

[maxwatt]

Perhaps lithium would be an interesting PGC-1alpha upregulator.
http://www.ncbi.nlm....pubmed/17451429

Lithium increases PGC-1alpha expression and mitochondrial biogenesis in primary bovine aortic endothelial cells.
Struewing IT, Barnett CD, Tang T, Mao CD.
Graduate Center for Nutritional Sciences, University of Kentucky, 900 Limestone Street, Lexington, KY 40536, USA.

Lithium is a therapeutic agent commonly used to treat bipolar disorder and its beneficial effects are thought to be due to a combination of activation of the Wnt/beta-catenin pathway via inhibition of glycogen synthase kinase-3beta and depletion of the inositol pool via inhibition of the inositol monophosphatase-1. We demonstrated that lithium in primary endothelial cells induced an increase in mitochondrial mass leading to an increase in ATP production without any significant change in mitochondrial efficiency. This increase in mitochondrial mass was associated with an increase in the mRNA levels of mitochondrial biogenesis transcription factors: nuclear respiratory factor-1 and -2beta, as well as mitochondrial transcription factors A and B2, which lead to the coordinated upregulation of oxidative phosphorylation components encoded by either the nuclear or mitochondrial genome. These effects of lithium on mitochondrial biogenesis were independent of the inhibition of glycogen synthase kinase-3beta and independent of inositol depletion. Also, expression of the coactivator PGC-1alpha was increased, whereas expression of the coactivator PRC was not affected. Lithium treatment rapidly induced a decrease in activating Akt-Ser473 phosphorylation and inhibitory Forkhead box class O (FOXO1)-Thr24 phosphorylation, as well as an increase in activating c-AMP responsive element binding (CREB)-Ser133 phosphorylation, two mechanisms known to control PGC-1alpha expression. Together, our results show that lithium induces mitochondrial biogenesis via CREB/PGC-1alpha and FOXO1/PGC-1alpha cascades, which highlight the pleiotropic effects of lithium and reveal also novel beneficial effects via preservation of mitochondrial functions.

I don't know.... When lithium is given for bipolar disorder, the patients tend toward substantial weight gain and complain of feeling "slow".

[rwac]

I don't know.... When lithium is given for bipolar disorder, the patients tend toward substantial weight gain and complain of feeling "slow".

Lithium enhances Dopamine uptake in vivo, that would explain weight gain and "feeling slow". Sounds like a completely different mechanism.

[url="http://"%20<a%20href="http://www3.interscience.wiley.com/journal/119640936/abstract?CRETRY=1&SRETRY=0""%20target="_blank">http://www3.intersci...nal...;SRETRY=0"</a>"]
EFFECT OF LITHIUM ON DOPAMINE UPTAKE BY BRAIN SYNAPTOSOMES[/url]

Edited by rwac, 16 January 2010 - 11:26 PM.

[DeadMeat]

I don't know.... When lithium is given for bipolar disorder, the patients tend toward substantial weight gain and complain of feeling "slow".

Lithium at dosages used for bipolar is very toxic, has side effects and is probably not really suitable for life extension anyway. But it is possible that low dosed chronic supplemental lithium(for example lithium orotate/aspartate) would still work a bit. As is apparently the case with lithium's bcl-2 up regulating and neurotrophic and neuroprotective effects(at least in rats). Although this is of course not known for PGC-1a at the moment. And it is actually not even known whether it would even work in vivo or for all types of cells.

http://www.ncbi.nlm....06/?tool=pubmed

Are "antimanic concentrations" of lithium required for its neurotrophic effects?

The aforementioned exciting results suggest lithium may have utility in the treatment of a variety of neuropsychiatric disorders associated with cell atrophy/loss and impairments of cellular resilience. One obvious concern is lithium's tolerability, especially in patients with neurodegenerative disorders. A series of studies were undertaken to determine if chronic administration of lithium at low doses also regulates bcl-2 expression. It was found that chronic (4 weeks) lithium administration, at doses that produce plasma levels of ~ 0.35 mM, robustly increases bcl-2 levels in rat frontal cortex and hippocampus (Goodwin and Jamison, 2007). Furthermore, 0.1–0.6 mM lithium robustly protects cultured cortical neurons from glutamate excitotoxicity (Hashimoto et al., 2002a). In middle cerebral artery occlusion, an in vivo model of stroke, lithium also provided significant protection at 0.5 mEq/kg (Ren et al., 2003). Overall, the data clearly suggest that considerably lower than "traditional antimanic" doses of lithium have neurotrophic and neuroprotective effects, and may have utility as adjunctive treatments for neuropsychiatric disorders associated with cell loss/atrophy.