Major aging gene found?

The following was written by fellow Mature Market Expert, David W. Moskowitz, MD, MA (Oxon.), FACP.  David is the Chairman, CEO & Chief Medical Officer of GenoMed, Inc. (see, I told you I’d give you all opportunities to share).

 Editor’s note: I have no investment or advisory role with GenoMed. I did, however, think that this topic might be of interest to you all. I look forward to your thoughts and observations.

 

 

 

Major aging gene found?

We found that over activity of angiotensin I-converting enzyme (ACE), specifically the ACE deletion/deletion (D/D) genotype, was associated with many common diseases, including renal failure (ref. 2 below).

This was in 1993, when ACE inhibitors had already been used for a decade. So what were nephrologists (including me) doing wrong?
 
It turned out the dose of ACE inhibitor we were using was too low, as was the hydrophobicity–how fat-loving the drug was (ref. 3).
 
Tissue (membrane-bound) ACE seems to require at least a 30 times higher dose to inhibit than serum ACE. The explanation may be the secretase that “bear-hugs” the ACE enzyme on the membrane, limiting access of substrate to the active site. Functionally, this could just take the form of the lid being “hugged” shut (ref. 5).
 
In any event, going up 5-fold on the dose of a hydrophobic ACE inhibitor, quinapril, did the trick (ref. 1). We were able to reverse diabetic and hypertensive kidney failure in white and black male veterans seen at the St. Louis VA Medical Center. An additional 800 white and black male veterans with normal kidney function were kept from progressing (ref. 1).
 
And, in unpublished data, 350 Hispanic men and women with diabetes were kept from renal progression at La Clinica, an indigent-care clinic in St. Louis.
 
One of the nice features of this first triumph of genomic epidemiology (1) is that ACE genotyping is not required: everybody seems to have too much ACE activity. Put another way, renal disease travels the same pathway in everybody, even though only about a third of patients show that ACE is part of the pathway.
 
I have high hopes for ACE inhibitors and ARBs in additional diseases (2,5-8,10). ACE is not only the “African gene (11),” responsible for the higher incidence of renal failure among blacks than whites, but probably the major aging gene for vertebrates (5). Just putting the country’s population above the age of 25 or 30 on the right ACE inhibitor at the right dose should extend life by a decade. It should also keep their pets healthier for several extra years, too.

And then if people agree to die at home rather than in the hospital, we might save healthcare costs by at least 10%.
 
GenoMed has applied for patent protection on this material, and would like our Next Generation DM(tm) to become the standard of care globally. Needless to say, a $25 billion a year industry prefers not to go out of business (9), so we need all the publicity we can get to save healthcare costs while improving patient outcomes. 
 
 
 
References
1:  Moskowitz DW. From pharmacogenomics to improved patient outcomes: angiotensin I-converting enzyme as an example. Diabetes Technol Ther. 2002;4(4):519-32.
PMID: 12396747. (For PDF file, click on paper #1 at: http://www.genomed.com/index.cfm?action=investor&drill=publications)

2:  Moskowitz DW. Is angiotensin I-converting enzyme a “master” disease gene? Diabetes Technol Ther. 2002;4(5):683-711. PMID: 12458570 (For PDF file, click on paper #2 at: http://www.genomed.com/index.cfm?action=investor&drill=publications)

3:  Moskowitz DW. Is “somatic” angiotensin I-converting enzyme a mechanosensor? Diabetes Technol Ther. 2002;4(6):841-58. PMID: 12685804 (For PDF file, click on paper #3 at: http://www.genomed.com/index.cfm?action=investor&drill=publications)

4:  Moskowitz DW. Pathophysiologic implications of angiotensin I-converting enzyme as a mechanosensor: diabetes. Diabetes Technol Ther. 2003;5(2):189-99. PMID: 12871609 (For PDF file, click on paper #4 at: http://www.genomed.com/index.cfm?action=investor&drill=publications)

5:  Moskowitz DW, Johnson FE. The central role of angiotensin I-converting enzyme in vertebrate pathophysiology. Curr Top Med Chem. 2004;4(13):1433-54. PMID: 15379656 (For PDF file, click on paper #6 at: http://www.genomed.com/index.cfm?action=investor&drill=publications)

6:  Moskowitz DW. Acute oxygen-sensing mechanisms. N Engl J Med. 2006 Mar 2;354(9):975-7. PMID: 16510756

 

 7: Williams RM, Moskowitz DW. The prevention of pain from sickle cell disease using trandolapril. J Natl Med Assoc 2007 Mar; 99(3):276-8 (http://www.nmanet.org/images/uploads/Publications/CR0276.pdf)

 8: ACE inhibitors and ARBs (angiotensin II receptor blockers) may turn out to be general viral antidotes, as described in Section 2151 of the Project BioShield II Act of April 28, 2005 (http://www.govtrack.us/congress/billtext.xpd?bill=s109-975), reproduced below:

CHAPTER 5–REPORT AND ADMINISTRATION

SEC. 2151. REPORT TO CONGRESS.

Not later than 180 days after the date of enactment of this Act, the Director of the Centers for Disease Control and Prevention, in consultation with the Assistant Secretary for Medical Readiness and Response of the Department of Homeland Security and the Director of the National Institute for Allergy and Infectious Disease of the National Institutes of Health, shall submit a report to Congress that describes alternatives to traditional vaccines and anti-viral therapeutics for viral diseases, including negative immunomodulation compounds that partially suppress a macrophage-dependent innate immune response of an individual to viral pathogens, in order to decrease morbidity and mortality from an excessive immune response.

 9. Moskowitz, DW. Promoting dialysis alternative. Letter. ACP Observer, Dec. 2006 (http://www.acponline.org/journals/news/dec06/letters.htm)

 10. Daily KC and Moskowitz DW. Unusually long MS remission with losartan. (Submitted).

 11. Moskowitz DW. Hypertension, thermotolerance, and the “African gene”: an hypothesis. Clin Exp Hypertens. 1996 Jan;18(1):1-19. PMID: 8822230

**************************************

David W. Moskowitz, MD, MA(Oxon.), FACP

Chairman, CEO & Chief Medical Officer

GenoMed, Inc.

“The public health company(TM)”

 

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