LONGECITY

Complete review...
http://findarticles....ag=content;col1

Upregulates T-REG best friend TGF-Beta
http://www.ncbi.nlm....pubmed/14741692

Downregulates STAT1/IFN-GAMMA and specially STAT3/IL-6 + STAT6/IL-4 (this both are worst T-REG enemy)... this may be no good for cancer but very good news for autoimmunity

http://www.ncbi.nlm....pubmed/19018808

http://www.ncbi.nlm....pubmed/19330073

Trough upregulating SOCS3 STAT6/IL4 also is downregulated.

http://www.ncbi.nlm....pubmed/21168220

Also psoriasis worst enemy IL17 reduced.
http://thorax.bmj.co...nt/64/1/44.long

ACTIVATES SIRT1 !
http://atvb.ahajourn...ract/30/11/2205

But can also be bad...
http://www.ncbi.nlm....pubmed/19120769
Edited by brunotto, 23 December 2010 - 11:48 PM.

Preparation, characterization, and anticancer effects of simvastatin-tocotrienol lipid nanoparticles.
http://www.ncbi.nlm....pubmed/20123009

Statins directly inhibit 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) activity, while gamma-tocotrienol, an isoform of vitamin E, enhances the degradation and reduces cellular levels of HMGR in various tumor cell lines

http://www.ncbi.nlm....pubmed/19777282

Looks like that taking statins with gamma-tocotrienol is quite a chemiotherapy (strong citostatic... like methotrexate)... better stay with alpha-tocopherol for those on statins...

http://www.ncbi.nlm....pubmed/19359655
Edited by brunotto, 24 December 2010 - 11:19 PM.

This thread lacks some easy to understand introduction, but when digging a little it seems to have coherent scientific content. Are you suggesting (/asking the question) that pravastatin (or other statins) could improve health and longevity for most people? or for which category of persons? or is this thread about something else?

Are you suggesting (/asking the question) that pravastatin (or other statins) could improve health and longevity for most people? or for which category of persons? or is this thread about something else?

Yes, I'm suggesting that Pravastatin can be usefull for people with autoimmune diseases, specially for thoose with th17 type (psoriasis, RA...) here a development of T-REG cells is needed (that help keep in check the autoimmune disease)

Also other statins can be... but Pravastatin look to be the safest and least interfering and most potent in reducing IL-6 (while less potent in reducing LDL)... and also cheap.

http://www.ncbi.nlm....pubmed/20158569

This is an interesting evolution of Pravastatin...
http://jpet.aspetjou.../1/419.abstract

Hope to see it in the future...
Edited by brunotto, 25 December 2010 - 10:28 AM.

Pravastatin increases expression of adiponectin.... and enhances insulin sensitivity in mice and humans... pravastatin promoting risk reduction for new onset of diabetes. Conversely, other statins including atorvastatin, rosuvastatin, and simvastatin all promote significant increase in this risk.

It's the safest both from the diabet risko point and methabolic (less interactions) "pravastatin and rosuvastatin are relatively hydrophilic and are not metabolized by cytochrome P450 3A4."

http://www.ncbi.nlm....pubmed/21130454
http://www.ncbi.nlm....pubmed/21115572

pravastatin, rosuvastatin and pitavastatin are not susceptible to any CYP inhibition.

http://www.ncbi.nlm....pubmed/20178046
Edited by brunotto, 25 December 2010 - 03:47 PM.

Very good also for fatty liver disease...

Activate Human PPARalpha Promoter and Increase PPARalpha mRNA Expression
http://www.ncbi.nlm....pubmed/19125197

LDL-C was decreased more potently in the LS than HS groups (-34% vs -19%; p=0.0069),

incidence of new Q-wave appearance in electrocardiogram was significantly lower (75% vs 89%; p=0.0056) in the HS(pravastatin; HS group; n=110)than LS(atorvastatin, fluvastatin, pitavastatin and simvastatin; LS group; n=131) groups.

CONCLUSIONS: In normocholesterolemic Japanese patients after AMI, hydrophilic pravastatin could be superior to lipophilic statins at preventing new Q-wave appearance and reducing cardiovascular events.

http://www.ncbi.nlm....pubmed/17721009

In the present study, pravastatin was the only hydrophilic
statin used, whereas several lipophilic statins were
administered: atorvastatin, fluvastatin, simvastatin and
pitavastatin. Hydrophilic statins are distributed much more
selectively in hepatocytes compared with lipophilic statins.17
Liver cellular membranes contain organic anion transporters
that mediate uptake of hydrophilic substances into
the cell. However, because extrahepatic cellular membranes
consist of lipid bilayers, hydrophilic statins cannot penetrate
these cellular membranes and thus cannot inhibit
intracellular HMG-CoA. Hence, whereas hydrophilic statins
are prevented from entering extrahepatic tissues, lipophilic
statins might inhibit not only cholesterol synthesis in the
liver but also production of essential substances by HMGCoA
reductase reaction, such as farnesylated proteins,
heme A, dolichol and ubiquinone (coenzyme Q10; CoQ10),
in peripheral compartments.17 CoQ10, an essential factor in
oxidative energy-generating systems in mitochondria, is
synthesized from mevalonic acid in many organs including
the heart.18 The mitochondrial inner membrane of heart
muscle has high activity of polyprenyltransferase, which
attaches isoprenoids to quinone bodies and is a key enzyme
in CoQ10 biosynthesis.19 It has been also reported that
upregulated CoQ10 biosynthesis in the heart is associated
with increased activity of HMG-CoA reductase.20 Lipophilic
statins that can enter easily myocardial cells inhibit isoprenoid
expression and thereby prevent CoQ10 biosynthesis in the
heart. This process could slow down mitochondrial generation
of ATP and affect myocardial contraction. Ichihara et
al reported that in a canine experimental myocardial ischemia
model, lipophilic statins worsened myocardial contractile
dysfunction during reperfusion, whereas pravastatin did
not.12,13 They also noted that worsening of myocardial
contraction was associated with reduction of myocardial
concentrations of CoQ10 and mitochondrial respiratory
function.21 Taken together, these mechanisms could explain
the superiority of hydrophilic vs lipophilic statins observed
in the present study.
Edited by brunotto, 25 December 2010 - 05:14 PM.

This thread lacks some easy to understand introduction, but when digging a little it seems to have coherent scientific content. Are you suggesting (/asking the question) that pravastatin (or other statins) could improve health and longevity for most people? or for which category of persons? or is this thread about something else?

I understand the reasoning for people to introduce the evidence they are presenting. I just find it funny that some of the more capable and intelligent people here complain of a lack of explanatory introduction. I really don't see what the big deal is here.

I thought it was obvious that the OP was suggesting that Pravastatin might be useful for treating autoimmune disorders. Then it appears that the OP is presenting evidence for other benefits that play a role in life extension. I have heard about statins being able to prevent heart attacks because of a mechanism different from that of the cholesterol, but I had not heard or read of the autoimmune benefits.

Effects of lovastatin and pravastatin on amyloid processing and inflammatory response in TgCRND8 brain.
Chauhan NB, Siegel GJ, Feinstein DL.

VA Chicago Health Care System-West Side Division, Chicago, IL 60612, USA. nchauhan@uic.edu

Abstract
Previous studies suggest that treatment with statins reduce beta amyloid (Abeta) deposition in brains of mouse models of Alzheimer's disease (AD) and may reduce the prevalence of AD in humans. Since lipophilicity influences the biological efficacy of statins, we compared the effects of lovastatin, a lipophilic statin, to effects of the hydrophilic pravastatin on amyloid processing and inflammatory responses in brain. Three-month old TgCRND8 mice expressing mutant human amyloid precursor protein (mHuAPP) were treated daily with various doses of either statin. After 1 month, levels of cerebral soluble and fibrillar Abeta peptides, soluble sAPPalpha, and inflammatory cytokines were measured. Both statins caused dose-dependent reductions in total Abeta peptides with parallel increases in total sAPPalpha. At all doses, slightly greater effects were observed with lovastatin than with pravastatin. In contrast, only lovastatin significantly increased levels of IL-1beta and of TNFalpha in a dose-dependent manner. Lovastatin, but not pravastatin, decreased succinic dehydrogenase and increased lactate dehydrogenase activities in skeletal muscle and increased TUNEL staining in liver. Our data demonstrate that both statins shift the balance of APP processing from excessive beta-toward the normal alpha-cleavage while reducing the total amyloid burden in TgCRND8 brain and that lovastatin, but not pravastatin, potentiates cerebral inflammation and is associated with liver and muscle histotoxicity in these animals. These data show that pravastatin can reduce amyloid burden without potentiating inflammatory responses in brain and, therefore, may have a wider dose-range of safety than have lipophilic statins in the treatment or prevention of AD.

In vitro myotoxicity of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, pravastatin, lovastatin, and simvastatin, using neonatal rat skeletal myocytes.

Pravastatin (IC50 = 759 microM) was > 100-fold less inhibitory of protein synthesis than lovastatin (IC50 = 5.4 microM) or simvastatin (IC50 = 1.9 microM).

http://www.ncbi.nlm..../pubmed/7878672

Angiotensin II-mediated oxidative stress and procollagen-1 expression in cardiac fibroblasts: blockade by pravastatin and pioglitazone.

http://www.ncbi.nlm....pubmed/16714359

Synergistic effects of pravastatin and pioglitazone in renal tubular epithelial cells induced by transforming growth factor-beta1.

http://www.ncbi.nlm....pubmed/17208021

"The combination of pravastatin and pioglitazone also blocked ANG II-mediated p38 MAPK and p44/42 MAPK activation. "

Seems that genetically the proteine psoriasirin production is upregulated in people suffering of psoriasis... psoriasirin is a potent chemioattractant for neutrofiles to skin

Psoriasirin is upregulated trough ERK (p44/42) and p38 intracellulars signals...

http://www.ncbi.nlm....les/PMC2440830/

IL-31 is elevated in psoriatic skin mast cells, MAPKs p38, ERK, and JNK are required for IL-31 production and release

http://www.ncbi.nlm....pubmed/20190140

5-lipoxygenase expression is regulated by NF-{kappa}B/ERK and Sp1/p38

http://www.ncbi.nlm....pubmed/20554538

Pravastatin (with aspirin) also decrease p38.... also vitamin E is usuefull and can replace Pravastatin+Asprin

http://www.cmj.org/P...81479672140.pdf
http://www.ncbi.nlm....pubmed/20176036

Metformin doesnt aktivate p38.... but activates ERK (p44/42)!!!
So attention with autoimmunity (good for cancer)...

Metformin acutely stimulated p44/p42 mitogenactivated protein (MAP) kinase in a dose- (3·2-fold at 1 mmol/l, P<0·05) as well as time-dependent (3·8-fold at 5 min, P<0·05) manner. This stimulation was highly selective since phosphorylation of intermediates in thestress kinase, janus kinase (JAK)–signal transducer and activator of transcription (STAT), and phosphatidylinositol (PI) 3-kinase signalling pathways such as p38 MAP kinase, STAT3, and Akt was unaltered.

http://joe.endocrino.../full/183/2/299

Histamine induced a time-dependent, H1 receptor-mediated activation of p38 MAP kinase (p38), p44/42 MAP kinase (ERK), and c-jun terminal NH2 kinase (JNK). Blocking of p38, ERK, or JNK with SB203580 (P<0.0001), PD98059 (P<0.0001), or SP600125 (P<0.0001), respectively, impaired histamine-induced TF expression in a concentration-dependent manner.

http://www.ncbi.nlm....pubmed/16009787
Edited by brunotto, 01 January 2011 - 05:55 PM.

Most probaly metformin is Ok... in some tissue metformin stimulates ERK in other it supresses.

These results suggest that metformin may attenuate the inflammatory responses, at least in part, by suppressing the production of both TNF and TF through the inhibition of the ERK1/2-Egr-1 pathway in human monocytes.
http://www.ncbi.nlm....pubmed/20371705

The findings demonstrate that in muscle AICAR and metformin activate aPKC via sequential activation of AMPK, ERK, and PDK1 and the AMPK/ERK/PDK1/aPKC pathway is required for metformin- and AICAR-stimulated increases in glucose transport.
http://www.ncbi.nlm....pubmed/19887597

A time-dependent activation of AMPK was observed in response to a number of stimuli, including globular adiponectin, 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR), or metformin. All these compounds significantly inhibited platelet-derived growth factor (PDGF)-stimulated proliferation and migration of human HSCs and reduced the secretion of monocyte chemoattractant protein-1.
http://www.ncbi.nlm....pubmed/18098312

Metformin dose-dependently inhibited IL-1beta-induced release of the pro-inflammatory cytokines IL-6 and IL-8 in human vascular smooth muscle cells (SMCs), macrophages (Mphis), and endothelial cells (ECs).... metformin suppressed IL-1beta-induced activation of the pro-inflammatory phosphokinases Akt, p38, and Erk, but did not affect PI3 kinase (PI3K) activity.
http://www.ncbi.nlm....pubmed/16385087