Re: [GRG] METFORMIN Activates + Increases AMPK — slows aging + lowers cancer risk.

As far as I know, there’s only one published report in mice that examines the effect of metformin on lifespan when initiated at different ages. The effect decreases with age of start. Consequently, in my opinion one should start any time after maturity. I myself started to take metformin since my 22nd birthday. I generally take 850mg in the morning and 425mg in the evening. 

The dose effect is also unclear. You may remember the Nature Communications paper in which 0.1% metformin extended lifespan while 1% shortened it. Most studies use mg/kg and when we converted these doses to mg/kg it turned out that the 0.1% was at the lower end of the normal dosage used in lifespan studies (100mg/kg) while the 1% was ridiculously high. 

In conclusion, one should start with metformin in early life but the optimal dose for life extension is unknown.  

2014-09-10 7:32 GMT+02:00 Thomas Coote :
Hi Karlis,
Thank you for your comments on that paper. 

I am a non-diabetic (57 y-o) who has been taking Metformin for about 2 years now, but I am only taking 250mg/day! The doses you quoted seem huge by comparison. Am I wasting my time/money?

Do you have any suggested age at which you recommend starting Metformin?

I presume Metformin would work in synergy with other AMPK activators?


Tom Coote

On Wednesday, September 10, 2014, Karlis C. Ullis, M.D. wrote:

Dear Members:

This explains why Metformin reduces cancer rates/risk since it activates the AMPK system. 

The data for Metformin RX cancer reduction  ( prostate, breast, colon, pancreas and others)  and cancer RX with Metformin is strong. 

The effective Metformin dose is about 1.5 GM is some studies. Some use the Metformin ER once daily.

I recommend 2.0 gm given as 1 gm twice daily to lower risk of acidosis. 

Bill Faloon of LEF has been a proponent of 850 mg Metformin  3x/day for long time. Even if you do not have diabetes Metformin is worth taking especially as you get older Glucose metabolism deteriorates subtly and cancer rates go up. That is also why hGH is bad idea since it impairs Glucose metabolism. 

Some say the AMPK  mechanism may knock-out pre-cancerous Stem Cells.  

Best of health


Karlis C. Ullis, MD

Endocrinology, Sports & Preventive Medicine900 Wilshire Blvd.,Suite 425; Santa Monica, CA 90401310.452.1990  Fax: 310.452.5134Email: note e-mails may not be checked regularly and should not be used for urgent medical matters. Information contained in this e-mail & attached document(s) may contain confidential information that is intended only for the addressee(s). If you are not intended recipient, you are advised  disclosure, copying, distribution, taking  any action in response to the information is prohibited. If you have received this e-mail in error, immediately notify sender & delete it. 

On Tue, Sep 9, 2014 at 3:00 PM, Patricia Tawfik wrote:

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[GRG] Increasing AMPK slows aging

Tue, Sep 9, 2014 8:15:59 PM delay the aging process by ‘remote control’Date:September 8, 2014Source:University of California – Los AngelesSummary:Biologists have identified a gene that can slow the aging process when activated remotely in key organ systems. The life scientists, working with fruit flies, activated a gene called AMPK that is a key energy sensor in cells. Increasing AMPK in the intestine increased the fly’s life by about 30 percent, and the fly stayed healthier longer as well. The research could have important implications for delaying aging and disease in humans.Share ThisActivating a gene called AMPK in the nervous system
induces the anti-aging cellular recycling process of autophagy in both the brain and intestine. Activating AMPK in the intestine leads to increased autophagy in both the intestine and brain. Matthew Ulgherait, David Walker and UCLA colleagues showed that this ‘inter-organ’ communication during aging can substantially prolong the healthy lifespan of fruit flies.Credit: Matthew Ulgherait/UCLA[Click to enlarge image]  UCLA biologists have identified a gene that can slow the aging process throughout the entire body when activated remotely in key organ systems.  Working with fruit flies, the life scientists activated a gene called AMPK that is a key energy sensor in cells; it gets activated when cellular energy levels are low.Increasing the amount of AMPK in fruit flies’ intestines increased their lifespans by about 30
percent — to roughly eight weeks from the typical six — and the flies stayed healthier longer as well.The research, published Sept. 4 in the open-source journal Cell Reports, could have important implications for delaying aging and disease in humans, said David Walker, an associate professor of integrative biology and physiology at UCLA and senior author of the research.”We have shown that when we activate the gene in the intestine or the nervous system, we see the aging process is slowed beyond the organ system in which the gene is activated,” Walker said.Walker said that the findings are important because extending the healthy life of humans would presumably require protecting many of the body’s organ systems from the ravages of aging — but delivering anti-aging treatments to the brain or other key organs could prove technically difficult. The study suggests that activating
AMPK in a more accessible organ such as the intestine, for example, could ultimately slow the aging process throughout the entire body, including the brain.Humans have AMPK, but it is usually not activated at a high level, Walker said.”Instead of studying the diseases of aging — Parkinson’s disease, Alzheimer’s disease, cancer, stroke, cardiovascular disease, diabetes — one by one, we believe it may be possible to intervene in the aging process and delay the onset of many of these diseases,” said Walker, a member of UCLA’s Molecular Biology Institute. “We are not there yet, and it could, of course, take many years, but that is our goal and we think it is realistic.”The ultimate aim of our research is to promote healthy aging in people.”The fruit fly, Drosophila melanogaster, is a good model for studying aging in humans because scientists have identified all of the fruit
fly’s genes and know how to switch individual genes on and off. The biologists studied approximately 100,000 of them over the course of the study.Lead author Matthew Ulgherait, who conducted the research in Walker’s laboratory as a doctoral student, focused on a cellular process called autophagy, which enables cells to degrade and discard old, damaged cellular components. By getting rid of that “cellular garbage” before it damages cells, autophagy protects against aging, and AMPK has been shown previously to activate this process.Ulgherait studied whether activating AMPK in the flies led to autophagy occurring at a greater rate than usual.”A really interesting finding was when Matt activated AMPK in the nervous system, he saw evidence of increased levels of autophagy in not only the brain, but also in the intestine,” said Walker, a faculty member in the UCLA College. “And vice
versa: Activating AMPK in the intestine produced increased levels of autophagy in the brain — and perhaps elsewhere, too.”Many neurodegenerative diseases, including both Alzheimer’s and Parkinson’s, are associated with the accumulation of protein aggregates, a type of cellular garbage, in the brain, Walker noted.”Matt moved beyond correlation and established causality,” he said. “He showed that the activation of autophagy was both necessary to see the anti-aging effects and sufficient; that he could bypass AMPK and directly target autophagy.”Walker said that AMPK is thought to be a key target of metformin, a drug used to treat Type 2 diabetes, and that metformin activates AMPK.The research was funded by the National Institutes of Health’s National Institute on Aging (grants R01 AG037514 and R01 AG040288). Ulgherait received funding support from a Ruth L. Kirschstein
National Research Service Award (GM07185) and Eureka and Hyde fellowships from the UCLA department of integrative biology and physiology.Co-authors of the research were Anil Rana, a postdoctoral scholar in Walker’s lab; Michael Rera, a former UCLA postdoctoral scholar in Walker’s lab; and Jacqueline Graniel, who participated in the research as a UCLA undergraduate.Story Source:The above story is based on materials provided by University of California – Los Angeles. The original article was written by Stuart Wolpert. Note: Materials may be edited for content and length.Journal Reference:1.Matthew Ulgherait, Anil Rana, Michael Rera, Jacqueline Graniel, David W. Walker. AMPK Modulates Tissue and Organismal Aging in a Non-Cell-Autonomous Manner. Cell Reports, 2014; DOI: 10.1016/j.celrep.2014.08.006 Cite This Page:MLA APA
ChicagoUniversity of California – Los Angeles. “Biologists delay the aging process by ‘remote control’.” ScienceDaily. ScienceDaily, 8 September 2014. .Sent using Hushmail


About Johnny Adams

My full-time commitment is to slow and ultimately reverse age related functional decline to increase healthy years of life. I’ve been active in this area since the 1970s, steadily building skills and accomplishments. I have a good basic understanding of the science of aging, and have many skills that complement those of scientists so they can focus on science to advance our shared mission. Broad experience Top skills: administration, management, information technology (data and programming), communications, writing, marketing, market research and analysis, public speaking, forging ethical win-win outcomes among stakeholders (i.e. high level "selling"). Knowledge in grant writing, fundraising, finance. Like most skilled professionals, I’m best described as a guy who defines an end point, then figures out how to get there. I enjoy the conception, design, execution and successful completion of a grand plan. Executive Director Gerontology Research Group (GRG). Manages Email discussion forum, web site, meetings and oversees supercentenarian (oldest humans, 110+ years) research. CEO / Executive Director Carl I. Bourhenne Medical Research Foundation (Aging Intervention Foundation), an IRS approved 501(c)(3) nonprofit. Early contributor to Supercentenarian Research Foundation. Co-Founder Geroscience Healthspan Forum. Active contributor to numerous initiatives to increase healthy years of life. Co-authored book on conventional, practical methods available today to slow the processes of aging – nutrition, exercise, behavior modification and motivation, stress reduction, proper supplementation, damage caused by improper programs, risk reduction and others. Fundamental understanding of, and experience in the genomics of longevity (internship analyzing and curating longevity gene papers). Biological and technical includes information technology, software development and computer programming, bioinformatics and protein informatics, online education, training programs, regulatory, clinical trials software, medical devices (CAT scanners and related), hospital electrical equipment testing program. Interpersonal skills – good communication, honest, well liked, works well in teams or alone. Real world experience collaborating in interdisciplinary teams in fast paced organizations. Uses technology to advance our shared mission. Education: MBA 1985 University of Southern California -- Deans List, Albert Quon Community Service Award (for volunteering with the American Longevity Association and helping an elderly lady every other week), George S. May Scholarship, CA State Fellowship. BA psychology, psychobiology emphasis 1983 California State University Fullerton Physiological courses as well as core courses (developmental, abnormal etc). UCLA Psychobiology 1978, one brief but fast moving and fulfilling quarter. Main interest was the electrochemical basis of consciousness. Also seminars at the NeuroPsychiatric Institute. Other: Ongoing conferences, meetings and continuing education. Aging, computer software and information technology. Some molecular biology, biotech, bio and protein informatics, computer aided drug design, clinical medical devices, electronics, HIPAA, fundraising through the Assoc. of Fundraising Professionals. Previous careers include: Marketing Increasing skill set and successes in virtually all phases, with valuable experience in locating people and companies with the greatest need and interest in a product or service, and sitting across the table with decision makers and working out agreements favorable to all. Information Technology: Management, data analysis and programming in commercial and clinical trials systems, and bioinformatics and protein informatics. As IT Director at Newport Beach, CA based technology organization Success Family of Continuing Education Companies, provided online software solutions for insurance and financial professionals in small to Fortune 500 size companies. We were successful with lean team organization (the slower moving competition was unable to create similar software systems). Medical devices: At Omnimedical in Paramount CA developed and managed quality assurance dept. and training depts. for engineers, physicians and technicians. Designed hospital equipment testing program for hospital services division. In my early 20’s I was a musician, and studied psychology and music. Interned with the intention of becoming a music therapist. These experiences helped develop valuable skills used today to advance our shared mission of creating aging solutions.
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