This content has not been reviewed within the past year and may not represent Web MD's most up-to-date information. To find the most current information, please enter your topic of interest into our search box. 1 risk factor for all the big diseases -- cancer, heart disease, Alzheimer’s -- is aging. But instead of treating the diseases, could a drug treat the aging process itself? That’s the idea behind a growing area of research drawing extensive support from both government and private donors, including millions from Silicon Valley executives like Microsoft co-founder Paul Allen and venture capitalist Peter Thiel. While federal science agency budgets have struggled in the past decade, funding at the National Institute on Aging has risen more than 50% since 2007. Researchers are seeking a drug to push back the most serious consequences of aging -- and keep people healthy, active, and alert years longer, a notion they call “health span.” “I’m not interested in creating a population that lives to be 200, because that would be a problem for the world we live in,” says Corinna Ross, Ph D, a biologist at Texas A&M University in San Antonio. “But if we can keep people out of nursing home care and reduce the number of Alzheimer’s and Parkinson’s patients, that would be ideal.” What scientists know about aging has advanced sharply in the past 2 decades as they learn more about what drives the aging process within cells. Epistemic Status: Pretty confident This is my first pass of a lit review of life-extension interventions apart from caloric restriction, with a focus on things that work in mammals (rather than fruit flies or other invertebrates.) Low methionine 60 Fischer rats fed a low-methionine diet lived 30% longer than control rats. 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They were 29% more likely to be “healthy” at baseline (free of cardiovascular disease, cancer, stroke, Parkinson’s, and diabetes, able to pass a walking and a cognitive test). “Combined statin and angiotensin-converting enzyme (ACE) inhibitor treatment increases the lifespan of long-lived F1 male mice.” AGE 38.5-6 (2016): 379-391. “Age of ovary determines remaining life expectancy in old ovariectomized mice.” Aging cell 2.3 (2003): 185-190. Proceedings of the National Academy of Sciences of the United States of America. The mutations were 85% more common in people who lived to more than 100 than in people who died at 72-74. A German sample of long-lived people found that minor alleles were 1.53x as common in centenarians than controls. Insulin-like growth factor signaling inhibits FOXO3 activity, while oxidative stress activates FOXO3. FOXO3 represses the m TOR pathway and promotes DNA repair. “Homocystinuria: a study with low-methionine diet in three patients.” Canadian Medical Association Journal 99.15 (1968): 731. “A familial form of congenital hypopituitarism due to a PROP1 mutation in a large kindred: phenotypic and in vitro functional studies.” The Journal of Clinical Endocrinology & Metabolism 89.11 (2004): 5779-5786. “Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans.” Science translational medicine 3.70 (2011): 70ra13-70ra13. “Functionally significant insulin-like growth factor I receptor mutations in centenarians.” Proceedings of the National Academy of Sciences 105.9 (2008): 3438-3442. “The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A.” Proceedings of the National Academy of Sciences 96.6 (1999): 3149-3153. “Pregnancy-associated plasma protein A as a marker of acute coronary syndromes.” New England Journal of Medicine 345.14 (2001): 1022-1029. “Metabolic consequences of pregnancy-associated plasma protein-A deficiency in mice: exploring possible relationship to the longevity phenotype.” Journal of Endocrinology 198.3 (2008): 599-605. “Resistance to age-dependent thymic atrophy in long-lived mice that are deficient in pregnancy-associated plasma protein A.” Proceedings of the National Academy of Sciences 106.27 (2009): 11252-11257. “Preferential impact of pregnancy-associated plasma protein-A deficiency on visceral fat in mice on high-fat diet.” American Journal of Physiology-Endocrinology and Metabolism 305.9 (2013): E1145-E1153. “Treatment with SRT1720, a SIRT1 activator, ameliorates fatty liver with reduced expression of lipogenic enzymes in MSG mice.” American Journal of Physiology-Endocrinology and Metabolism 297.5 (2009): E1179-E1186. “A pilot randomized, placebo controlled, double blind phase I trial of the novel SIRT1 activator SRT2104 in elderly volunteers.” PLo S One 7.12 (2012): e51395. “SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1.” Journal of Biological Chemistry 285.11 (2010): 8340-8351. “A phase II, randomized, placebo‐controlled, double‐blind, multi‐dose study of SRT2104, a SIRT1 activator, in subjects with type 2 diabetes.” British journal of clinical pharmacology 78.1 (2014): 69-77. “Caloric restriction, SIRT1 and longevity.” Trends in Endocrinology & Metabolism 20.7 (2009): 325-331. “Markedly attenuated acute and chronic pain responses in mice lacking adenylyl cyclase‐5.” Genes, Brain and Behavior 6.2 (2007): 120-127. “Motor dysfunction in type 5 adenylyl cyclase-null mice.” Journal of Biological Chemistry 278.19 (2003): 16936-16940. “Adenylyl cyclase type 5 (AC5) is an essential mediator of morphine action.” Proceedings of the National Academy of Sciences of the United States of America 103.10 (2006): 3908-3913. It is also anti-inflammatory: suppresses IL-2 and IL-6, reduces proliferation of T cells and lymphocytes, reduces inflammation. FOXO3 is activated by AMPK. You can do this via metformin in vitro — meanwhile changing glioma precursor cells into non-tumor cells. You can also do it with AICAR, an AMP analogue that stimulates AMPK. Note that AICAR reduces triglycerides, increases HDL, lowers blood pressure, and reverses insulin resistance in mice. Unsupported Musings I don’t think antioxidants generally have come out looking too good for anti-aging, and there are a lot of counterexamples to the “aging is oxidative damage” hypothesis. ““Disappearance” of cystinuria in a patient treated with prolonged low methionine diet.” Metabolism 16.4 (1967): 378-381. I think the growth-hormone-and-insulin-signaling cluster of life extension techniques and mutations is probably a real thing, and matches well to an explanation for why caloric restriction works.
Dosing chart for metformin including dosage forms, dosing recommendations, food effects, generic availability, and dosing is for ADULTS unless otherwise specified. P = drugs with pediatric dosing recommendations. METFORMIN. Metformin Anti-Aging Diabetes Drug Can Extend Life To 120 Years, Experts Say By Staff Reporter Dec 03, 2015 AM EST A cheap drug widely used for type 2 diabetes turns out to have anti-aging properties that can potentially allow humans to increase their lifespan by about 50 percent and live up to 120 years old.