Medical Forum / General / General / December 2004
ACE Inhibition Is Partial "Fountain Of Youth"
|
|
Thread rating:  |
doe - 14 Dec 2004 11:29 GMT http://www.biospace.com/news_story.cfm?StoryID=18425620&full=1
University of California, Irvine Researcher Confirms GenoMed, Inc.'s Patent-Pending Discovery: ACE Is Major Aging Gene, ACE Inhibition Is Partial "Fountain Of Youth"
Who loves ya. Tom
 Signature Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man Is A Herbivore! http://pages.ivillage.com/ironjustice/manisaherbivore DEAD PEOPLE WALKING http://pages.ivillage.com/ironjustice/deadpeoplewalking
Sbharris[atsign]ix.netcom.com - 15 Dec 2004 01:42 GMT > http://www.biospace.com/news_story.cfm?StoryID=18425620&full=1 > > University of California, Irvine Researcher Confirms GenoMed, Inc.'s > Patent-Pending Discovery: ACE Is Major Aging Gene, ACE Inhibition Is Partial > "Fountain Of Youth" COMMENT:
An interesting story. This company is convinced that Angiotensin Converting Enzyme (ACE) gene alleles of various kinds are associated with rapid aging syndromes, which could be modulated by ACE inhibitors. Of course, what the article doesn't tell you is that ACE inhibitor compounds have been part of medicine for more than 20 years. These compounds general end with the suffix "-pril", as for example Captopril (capoten) which was the first one commercially available.
This is all starting to get interesting, however, because there have been suggestions for some time that ACE inhibitors do more beneficially for people than just lower blood pressure (their ostensible use). In fact, they are vaguely reminiscent of the statins in being overall "tonics" for diabetics, interfering in all kinds of diabetic angio and arteriolar complications by mechanisms uncertain.
Recently, angiotensin II ("AII", a major regulatory peptide which results, after two steps, from ACE action) has been implicated in the formation of fibrous changes in the heart. These cause the ventricular stiffness which is seen not only in chronic hypertension, but also to some extent in normal aging, even if people are never hypertensive. Everybody's left ventricle and arteries lose elasticity with age.
And so do their lungs, all of which is replaced by fibrous tissue. These changes in the lungs result in the well-known decrease in Forced Expiratory Volume (1 sec) which is one of the aging changes which is most robust and least susceptible to positive modification, in longitudinal aging studies. That is, you can always make your FEV(1) drop faster by smoking or mistreating your lungs, but there's nothing you can do, exercise included, to stop its normal non-pathological age-related decline. If ACE or AII have anything to do with any of these changes, in normal aging heart OR lungs, it would be a very, very exciting result. Previously, we've had absolutely nothing to use to modify these processes which replace youthful elastic fibers with e lderly stiff fibrous collagen.
ACE action is part of the body's regulatory action, and ACE inhibition, even partial inhibition, does sometimes have unacceptable side effects. Interestingly, ACE does more than make AII. It also helps to break down bradykinin, a major inflammatory mediator. So if you inhibit ACE, bradykinin goes up, and so does inflammation in some places (whether inflammation from bradykinin or anti-inflammation from less AII wins out, depends on the tissue). Inflammation in some cases might be a good thing, for it increases blood flow (for example, perhaps in heart arterioles). In some cases, ACE inhibition causes enough new bradykinin release to cause angioedema or at least a chronic irritative cough.
More recently, however, a number of angiotensin II blocking drugs (ATB drugs), which directly act at the AII receptor, have become available in medicine, and these may also end up doing more than simply lowering blood pressure. So we have a very, very specific way of blocking AII effects in humans, and these drugs are already well tested, quite benign, and long-approved pharmaceuticals (they typically end in the suffix "-sartan" as in olmesartan = Benicar). Will either ACE inhibitors or ATBs turn out to have anti-aging properties? This whole area is one to watch.
SBH
Kofi - 16 Dec 2004 04:18 GMT There are also a number of naturally occurring ACE inhibitors found in the diet - grape seed extract, for instance. This might account for some of the longevity seen among red wine drinkers.
tcarter2@elp.rr.com - 16 Dec 2004 05:40 GMT Hi Steve, Nice review, I hadn't known about the bradykinin/cough relationship. Perhaps the various anti-inflammatories many of us take will help in this respect. I too wish the 20 yr record of ACE inhibitors was a bit better. Studies generally show a mortality reduction of 10-20%. One's first reaction to this might be that a much smaller reduction in mortality would be expected in the general population, but I don't see it that way for the following reasons. While it's generally taken as gospel that hi blood pressure shortens life span by causing heart attacks and stroke there is, in my minority view no convincing evidence for this. Yes, there is a clear relationship (OR's are between two and three in observational studies), but when blood pressure (BP) is reduced by any one of four BP drugs, there is no concurrent reduction in mortality. These drugs are calcium channel blockers, diuretics, alpha blockers, and angiotensin receptor blockers. The results of many trials showing this more or less prove that either blood pressure reduction doesn't extend life, or that side effects of all four just about exactly cancel out the benefits. (more than cancel out in the case of alpha blockers.) Occam says that the best guess is the former and that the apparent relationship is due to the fact that something else is causing both hi blood pressure and the vascular incidents. Beta blockers and ACEi do show a mortality benefit, but if it's due to the reduction of blood pressure what's wrong with the other four drugs? Beta blockers inhibit the action of adrenaline and noradrenalin this reduces stress and may well the mechanism for the very moderate life extension by beta blockers. As for the ACEi, Doug has shown life extension in two trials with drosophila, Tim has posted a sound study suggesting strong mitochondrial benefits, and I've posted papers showing cancer, and neurodegeneration benefits, protection from calcification thru Klotho, an antiaging gene, and reversal of carotid atherogenesis in a small human intervention trial. This last is a trial with pomegranate juice (as were Doug's experiments) which, based on skimpy evidence is by far the best ACEi with action that not only goes beyond BP reduction, but also beyond ACE inhibition itself, and with BP and ACE inhibition equal to the drugs. If ACEi cause a 10-20% reduction in mortality in heart patients without benefiting them thru BP reduction it seems quite possible that a similar benefit will be seen in the general population, perhaps even better with long term use. In summary I too, believe this issue bears watching, am not quite as apprehensive as Steve over the moderate life extension so far shown in short term trials of patients, and ask the question, is the risk/benefit ratio for drinking a glass of pomegranate juice low enough to warrant this intervention by life extensionists? Thomas
Sbharris[atsign]ix.netcom.com - 16 Dec 2004 22:23 GMT Thomas:
In the very large ALLHAT study the "diuretic" antihypertensive chlorthalidone did better at decreasing morbitity and mortality than did the ACE drug. Things aren't as simple as you paint them. http://www.aafp.org/afp/20040701/fpin.html
Steve
tcarter2@elp.rr.com - 17 Dec 2004 23:13 GMT Hi Steve, Yes, quite true and very consistent with about a half dozen other trials comparing ACEi with other classes of blood pressure drugs. ACEi are not used as stand alone treatments in hypertension for that very reason, they are one of the types of drugs that don't reduce mortality in heart patients over the 2 to 5 yrs that most trials run. But this is niether my point nor yours, we are both discussing the possible anti-aging aspects of ACEi. The 10 to 20% reduction in mortality I refered to is for ACEi vs placebo as a second line treatment, mostly with thiazides, a type of diuretic that does get about a 10% reduction in mortality as a stand alone treatment. Some beta blockers get about the same and ACEi along with other types get little or none. What you believe bears watching is the long term potential for ACEi as an anti-aging intervention. While I agree I also intend to do a bit more than watch while waiting for elucidation. And I intend watch closely to see which ACEi gives the best results while supplementing with one which I think already has displayed a satisfactory risk/benefit ratio.
Thomas
RArmant - 18 Dec 2004 00:22 GMT >What you believe bears watching is the long term potential for >ACEi as an anti-aging intervention. While I agree I also intend to do a >bit more than watch while waiting for elucidation.
>And I intend watch >closely to see which ACEi gives the best results while supplementing >with one which I think already has displayed a satisfactory >risk/benefit ratio. Which ACE inhibitor would that be?
tcarter2@elp.rr.com - 18 Dec 2004 20:59 GMT Hi, RArmant, Pomegranate juice, Google it in sci.life-extension for evidence from peer reviewed journals showing it to be as good as the prescribed drugs at BP reduction and ACE Inhibition, and AFAIK the best treatment known to man for reducing atherosclerosis, the biggest killer known to man. (If a small intervention trial I posted is verified) I will also to take this opportunity to clarify my remarks as they were I think not very well written. Drugs that reduce blood pressure do not in general extend life span in hypertensives at hi risk for heart attacks. This signifies to me that hi blood pressure is not the killer its made out to be, perhaps within reasonable limits not a killer at all. In fact Ive posted studies showing high BP is related to slower brain aging and extended life span in studies done on elderly people. Some BP drugs do give a modest 10% reduction in mortality. Logically it would seem this is due to effects other than reduction in BP. ACEi are not a good stand alone treatment for BP in general. One of their protective mechanisms seems to be that they inhance the bodies natural antioxidative defenses. This effect may not be strong enough to give protection to heart disease patients who are already well down the road to heart failure. For those who are more healthy, and especially older ones, who suffer more from oxidative stress they may well be the best when given long term. See the paper I post below which indicates so. Note that this study ran for four years which is one of the longer ones. Even if not true, ACEi are well known to be life extending when given with other BP drugs. These facts indicate that ACEi are beneficial to people with hi BP and at hi risk for heart attacks, are probably beneficial to normaly healthy people, and may be an authentic anti aging intervention. For normal healthy people natural health products long recognized as safe which inhibit the ACE would seem to be indicated. They are among others. Sour milk, bonito, tea, salt, grape seed/skin extract, and pomegranate juice which is by far the strongest and best researched in this respect. There is some evidence that each of these substances is life extending.
N Engl J Med. 2003 Feb 13;348(7):583-92. Related Articles, Links Comment in: ACP J Club. 2003 Sep-Oct;139(2):38. Expert Opin Pharmacother. 2003 May;4(5):825-8. J Fam Pract. 2003 Jun;52(6):436-8. N Engl J Med. 2003 Feb 13;348(7):639-41. N Engl J Med. 2003 Jul 3;349(1):90-3; author reply 90-3. N Engl J Med. 2003 Jul 3;349(1):90-3; author reply 90-3. N Engl J Med. 2003 Jul 3;349(1):90-3; author reply 90-3. N Engl J Med. 2003 Jul 3;349(1):90-3; author reply 90-3. N Engl J Med. 2003 Jul 3;349(1):90-3; author reply 90-3. A comparison of outcomes with angiotensin-converting--enzyme inhibitors and diuretics for hypertension in the elderly. Wing LM, Reid CM, Ryan P, Beilin LJ, Brown MA, Jennings GL, Johnston CI, McNeil JJ, Macdonald GJ, Marley JE, Morgan TO, West MJ; Second Australian National Blood Pressure Study Group. School of Medicine, Flinders University, Adelaide, Australia. BACKGROUND: Treatment of hypertension with diuretics, beta-blockers, or both leads to improved outcomes. It has been postulated that agents that inhibit the renin-angiotensin system confer benefit beyond the reduction of blood pressure alone. We compared the outcomes in older subjects with hypertension who were treated with angiotensin-converting-enzyme (ACE) inhibitors with the outcomes in those treated with diuretic agents. METHODS: We conducted a prospective, randomized, open-label study with blinded assessment of end points in 6083 subjects with hypertension who were 65 to 84 years of age and received health care at 1594 family practices. Subjects were followed for a median of 4.1 years, and the total numbers of cardiovascular events in the two treatment groups were compared with the use of multivariate proportional-hazards models. RESULTS: At base line, the treatment groups were well matched in terms of age, sex, and blood pressure. By the end of the study, blood pressure had decreased to a similar extent in both groups (a decrease of 26/12 mm Hg). There were 695 cardiovascular events or deaths from any cause in the ACE-inhibitor group (56.1 per 1000 patient-years) and 736 cardiovascular events or deaths from any cause in the diuretic group (59.8 per 1000 patient-years; the hazard ratio for a cardiovascular event or death with ACE-inhibitor treatment was 0.89 [95 percent confidence interval, 0.79 to 1.00]; P=0.05). Among male subjects, the hazard ratio was 0.83 (95 percent confidence interval, 0.71 to 0.97; P=0.02); among female subjects, the hazard ratio was 1.00 (95 percent confidence interval, 0.83 to 1.21; P=0.98); the P value for the interaction between sex and treatment-group assignment was 0.15. The rates of nonfatal cardiovascular events and myocardial infarctions decreased with ACE-inhibitor treatment, whereas a similar number of strokes occurred in each group (although there were more fatal strokes in the ACE-inhibitor group). CONCLUSIONS: Initiation of antihypertensive treatment involving ACE inhibitors in older subjects, particularly men, appears to lead to better outcomes than treatment with diuretic agents, despite similar reductions of blood pressure. Copyright 2003 Massachusetts Medical SocietyPMID: 12584366
christopher.a.dowling@gmail.com - 18 Dec 2004 01:29 GMT Do you think there's any merit to "natural" ACE inhibitors, such as the katuobishi oligopeptide?
Hua Kul - 17 Dec 2004 15:34 GMT Dr. Moskowitz has been quite open to direct email exchanges if you want to correspond. His treatment aims at reducing tissue levels of ACE, or blocking ACE receptors, or a combination. He has had very good success in helping patients recover from West Nile virus.
He currently has an application on the Genomed web site to take part in his study for use of ACE inhibitors against influenza. You can print it out and take it to your doctor for "admission" to the trial. It might be more beneficial than a flu vaccine.
Here's a brief interview with him: http://www.chronicfatiguesupport.com/library/showarticle.cfm/ID/5007/e/1/T/CFIDS_FM/
==================================================================
I began studying the angiotensin I-converting enzyme or "ACE" gene ten years ago, while still in academia. My lab found that over-activity of ACE was responsible for kidney failure due to diabetes and high blood pressure. What was surprising was that another 150 or so diseases seemed to be caused by too much ACE activity.
Our approach is to attack diseases at their source, so as to achieve regression ("cure"). It just so happens that ACE appears to be at the source of virtually all common diseases except prostate cancer. In particular, all autoimmune diseases, such as Lupus, Rheumatoid Arthritis, Multiple Sclerosis, and even allergies to penicillin and sulfa drugs, start with overactivity of ACE. The logical treatment to try, then, especially for diseases with no good treatment yet, is an ACE inhibitor or an angiotensin II blocker (ACE makes angiotensin II).
..............................
But the symptoms of CFS and FM most resemble the flu, and suggest the work of the monocyte/macrophage, a key player in the host's innate immune response. Tumor necrosis factor-alpha (tnf-alpha, or cachectin) is just one of many hormones released by activated macrophages. In fact, most of the symptoms of the flu (muscle aches or "myalgias," weakness, fatigue) are due to release of hormones from macrophages.
Since activated macrophages express ACE on their surface membrane, ACE has something to do with their activated state. The product of ACE, angiotensin II, is probably an activating hormone, or "cytokine," for macrophages. Blocking the macrophage with an ACE inhibitor or angiotensin II receptor blocker ("arb") is a very gentle, benign way of trying to tone down the inflammation. We have seen it work for several diseases already characterized by overly exuberant inflammation or even outright autoimmune disease. ================================================================== --Hua Kul
Daniel Prince - 17 Dec 2004 20:56 GMT >But the symptoms of CFS and FM most resemble the flu, and suggest the >work of the monocyte/macrophage, a key player in the host's innate >immune response. Tumor necrosis factor-alpha (tnf-alpha, or cachectin) >is just one of many hormones released by activated macrophages. In >fact, most of the symptoms of the flu (muscle aches or "myalgias," >weakness, fatigue) are due to release of hormones from macrophages. Please post this entire message on alt.med.cfs. Thank you for posting it on sci.med and in advance for posting it on alt.med.cfs. -
 Signature I am TERRIBLY cruel to my cat. I tease him with a vine tendril until he either jumps up in the air to bat at it or zooms around in a circle until he gets too dizzy to stand up. What is cruel about it is that I don't do it nearly as much as he wants me to.
Hua Kul - 22 Dec 2004 05:53 GMT > Please post this entire message on alt.med.cfs. Thank you for > posting it on sci.med and in advance for posting it on alt.med.cfs Daniel, I posted the topic several days ago on alt.med.cfs but it has not yet appeared. It's a moderated group so I don't know what else I can do. There have been other new topics posted since I submitted this one.
--Hua Kul
Daniel Prince - 22 Dec 2004 07:06 GMT >> Please post this entire message on alt.med.cfs. Thank you for >> posting it on sci.med and in advance for posting it on alt.med.cfs [quoted text clipped - 5 lines] > >--Hua Kul May I post it for you? I will make it clear that the original message was from you.
 Signature I am TERRIBLY cruel to my cat. I tease him with a vine tendril until he either jumps up in the air to bat at it or zooms around in a circle until he gets too dizzy to stand up. What is cruel about it is that I don't do it nearly as much as he wants me to.
gmp@adres.nl - 22 Dec 2004 13:27 GMT > >> Please post this entire message on alt.med.cfs. Thank you for > >> posting it on sci.med and in advance for posting it on alt.med.cfs [quoted text clipped - 12 lines] > until he either jumps up in the air to bat at it or zooms around > in a circle until he gets too dizzy to stand up. What is cruel about
> it is that I don't do it nearly as much as he wants me to. Feel free to post the article under your own name if you would like, no problem.
--Hua Kul
|
|
|