Recently, many media have reported that “the first anti-aging drug will be clinically tested next year”. It is said that a drug called metformin can “prolong the life of the animal” and it is expected to “live up to 120 years old”. By taking medicine to prolong life, can such a sci-fi thing really come true?
The world's first anti-aging drug will be clinically tested next year, and the results may make distant diseases such as Alzheimer's disease and Parkinson's disease.4255-62-3
The British "Daily Telegraph" website reported on December 1 that scientists now believe that it is possible to delay the aging of people and make them healthy to live in their 110s and even 120s.
Although this may sound like science fiction, researchers have shown that metformin used to treat diabetes can extend the lifespan of animals. The US Food and Drug Administration has now approved the clinical trial to verify whether the drug produces the same effect on humans.
If the trial is successful, it means that the 70-year-old is biologically as healthy as the 50-something. This may open a new era for gerontology. By then, doctors will no longer have to treat cancer, diabetes and dementia separately, but only for the fundamental mechanism of aging.
Scottish anti-aging expert, Professor Gordon Lithgow of the Buck Institute on Aging in California, USA, is one of the consultants for the above research. He said: "If you take the aging process as a research object and delay aging, then you will also delay all aging-related diseases. This is revolutionary and unprecedented."344-14-9
Aging is not an inevitable part of life, because all cells contain a DNA blueprint that allows the body to work forever. Some marine life does not age at all.
But in our lifetime, we must go through billions of cell divisions in order to maintain the normal functioning of the body. The more the number of cell divisions, the more errors will sneak into the process. As cell problems increase, the body will eventually be unable to repair the damage. In the case of cancer, cells no longer have the ability to get rid of mutations, and tumors continue to develop. In the case of Alzheimer's disease, once the brain stops cleaning the amyloid plaque, people will develop symptoms of dementia.3674-09-7
Scientists believe that the best anti-aging drug candidate is metformin. It is the most widely used hypoglycemic agent in the world, taking it for only 10 pence a day (about 15 cents). Metformin increases the amount of oxygen molecules released into cells, which seems to increase the body's robustness and prolong life.
When Belgian researchers tested metformin on C. elegans, these nematodes not only slowed down, but also prolonged their health. Their speed of activity did not slow down, nor did they grow wrinkles. After using metformin in mice, their lifespan was extended by nearly 40% and bones became stronger. Last year, Cardiff University in the United Kingdom found that after taking metformin in diabetic patients, they actually live longer than non-diabetics, although in theory diabetes should give them an average life expectancy of 8 years.
The clinical trial, called "Metformin against aging," is scheduled to begin in the US next winter. Currently, scientists from a variety of institutions are raising funds and recruiting 3,000 older people between the ages of 70 and 80 who have or may have cancer, heart disease and dementia in the future. They are looking forward to demonstrating that metformin can delay aging and prevent the onset and development of disease.
The MedSci editor retrieved ClinicalTrials, which has not yet been retrieved, but will continue to track the dynamics of this research. There is a large body of research on clinical Trials for metformin treatment of various types of tumors.
Metformin has good efficacy and safety evidence for single-agent, combination therapy, and good evidence of health economic benefits. Whether for glycemic control or prevention of cardiovascular complications of diabetes, it has been clearly confirmed in the clinic.
Since its inception in 1957, metformin has been used internationally for nearly 60 years and has been used in China for nearly 20 years. Metformin is the ace of first-line medication in various types of diabetes prevention and treatment guidelines. With the release of large-scale research results, the scope of metformin has been further expanded. It has been approved for use in children over 10 years old. The American Diabetes Association (ADA) has allowed it to be used in patients with hyperglycemia during pregnancy, with a safety level equivalent to insulin during pregnancy.
In 2014, China's "Metformin Clinical Application Expert Consensus" was released, which standardized its use methods and drug combinations, and put forward more accurate requirements for special populations. In the previous article, we reported on the miraculous functions of metformin in addition to hypoglycemic, including improving intestinal flora, lowering blood lipids, lowering cardiovascular risk factors, and applications in obese children and obese pregnant non-diabetic women. (Read above can be viewed by clicking the "Read the original" button at the end of the article), but the surprises brought by Metformine are much more than that. In recent years, a large number of studies have found that metformin also has "specific functions" for anti-aging and anti-cancer:
The magical effect of metformin on anti-aging
1. Metformin can prolong the lifespan of patients with type 2 diabetes, even longer than non-diabetics
A large-scale study involving 180,000 people found that patients with type 2 diabetes who were taking metformin for a long time had a higher life expectancy than non-diabetics, and metformin was also beneficial for the health of non-diabetics.
The researchers studied the survival of patients with type 2 diabetes who took metformin and sulfonylureas, and compared their life expectancy with matched non-diabetic patients, age, sex, smoking, and others. The clinical status and other indicators are matched. The results showed that compared with non-diabetic patients, the quality of life of diabetic patients taking metformin was significantly improved, and life expectancy was higher; the quality of life of individuals taking sulfonylureas was reduced, and their life expectancy was also reduced.
The research leader Professor Craig Currie said: "Metformin has anti-cancer effect, it can also help people resist the intrusion of cardiovascular disease, and can also reduce the incidence of high-risk people with diabetes, reducing the risk effect by up to 1/3. ."
Source: Diabetes Obes Metab, 2014, 16(11): 1165-1173.
2. Metformin strengthens healthy cells and prolongs cell life
A study from Belgium found that metformin increases cell sturdiness and longevity by promoting the release of toxic oxygen molecules in cells, which ultimately reduces body aging and prolongs individual life.
Through the study on the anti-aging mechanism of metformin in C. elegans, it is found that with the aging of Caenorhabditis elegans, the individual will gradually become smaller, the whole body folds, and finally the ability to exercise slowly decreases, but the intervention with metformin The body size of the nematode is significantly reduced in speed and wrinkling speed, which not only slows down the aging rate, but also restores to a healthy state.
The researchers say that as the molecular weight of the harmful active oxygen released in the cells is reduced, it will have a long-lasting beneficial effect on the cells. Before reactive oxygen species are toxic to cells, cells typically make effective use of reactive oxygen species, and metformin often causes a slight increase in harmful reactive oxygen species in the cells, making cells stronger and prolonging the lifespan of healthy cells.
3. Metformin or anti-aging drugs
Researchers from University College London co-cultured nematodes with E. coli and tested the effects of metformin on these nematodes. It was found that metformin treated with metformin would last longer only if co-cultured E. coli was sensitive to the drug.
Throughout the study, metformin was treated for a total of 6 days, about 1/3 of the normal lifespan of nematodes, either by altering the metabolism of bacteria in the nematode, and thereby limiting the ability of the nematode host to obtain nutrients. A similar effect to limiting diet.
4. Metformin can promote the health of mice and prolong their life.
A study published in Nature Communications showed that regular administration of small doses of metformin during the middle age promoted the health and longevity of mice, whereas larger doses of metformin shortened their lifespan.
The study group tested 0.1% and 1.0%, respectively. The results showed that the survival of the 0.1% dose group was extended by about 6% compared with the group without metformin, but the life expectancy of the 1.0% dose group was shortened by more than 14 times. %, the latter may be due to renal failure, and the 0.1% dose group does not appear to have any effect on the kidneys.
Studies have shown that metformin appears to promote the efficiency of the use of lipogenic energy in mice. As mice age, metformin also helps the body maintain weight, a feature associated with prolonged survival. Metformin also prevents the development of metabolic syndrome and appears to exert an antioxidant effect in mice.
Rafael de Cabo, the research leader, said: "Aging is a driving force behind metabolic syndrome and diabetes. Given the clinical evidence that metformin can alleviate the symptoms of these diseases and reduce the risk of cancer, we think it may be a good candidate. Can be used to study its broader impact on health and longevity."
Source: Nat Commun, 2013, 4: 2192.
5. Metformin anti-aging clinical trial or initiation
Professor Nir Barzilai, a scientist at the Albert Einstein College of Medicine in New York, USA, is preparing to submit an application to the FDA, hoping to conduct a clinical trial to study the anti-aging effects of metformin. The FDA welcomes this proposal and believes that this idea is worth considering.
The subjects will mainly include patients with cancer, heart disease and cognitive dysfunction, and need not have type 2 diabetes, because people with diabetes may be able to take the drug, even if it is effective, it does not explain the problem. The project plans to track 3,000 elderly people over the age of 70 for five consecutive years. At present, the main obstacle is the lack of funds, which requires $50 million.
Matt Kaeberlein of the University of Washington believes that Barzilai's research plan is reasonable. Although animal experiments have found that the anti-aging effects of other drugs are stronger, the long-term clinical application history of metformin is an important basis. If approved, this will be the first clinical trial of anti-aging drugs in humans.
Source: UK Daily Mail website
The magical effect of metformin on cancer
1. Anticancer effect of metformin
Research published by the Department of Immunology, Okayama University, Japan, in the Proceedings of the National Academy of Sciences, shows that metformin prevents CD8+ TILs from decreasing due to apoptosis by increasing the number of tumor CD8+ infiltrating lymphocytes (TILs). effect.
TILs are a special type of tumor-aggressive immune cells. These cells can directly attack tumor cells. The number is closely related to the survival rate of patients. The number can avoid the apoptosis caused by immune reaction, which may be the cytological basis of metformin anticancer. .
This study suggests that metformin may have unexpected effects in combination with various anti-cancer immunotherapies.
2. "God medicine" metformin inhibits the progression of pancreatic cancer
Researchers from the Massachusetts General Hospital have discovered a new mechanism by which metformin, a diabetes treatment, inhibits the progression of pancreatic cancer.
In the study, first, the researchers found that for overweight or obese patients treated with metformin, the amount of hyaluronic acid in an extracellular matrix component of the tumor sample was 30% less than that of patients who did not take metformin. . In a mouse model of pancreatic cancer obesity, metformin treatment also reduced the expression of hyaluronic acid and type 1 collagen, while also having fewer activated pancreatic stellate cells (PSCs). Researchers using cultured cells have found that metformin inhibits the signaling pathways used by PSCs to synthesize hyaluronic acid and type 1 collagen, while also preventing the recruitment of tumor-associated macrophages.
The researchers say that an in-depth understanding of the mechanisms by which metformin inhibits cancer progression can help identify potential biomarkers and help cancer patients better choose drugs.
Source: PLoS One, 2015, 10(12): e0141392.
3. The mechanism of metformin inhibiting esophageal cancer has been proven
The research team led by Zhang Wei, a professor at Shantou University Medical College, discovered the mechanism of action of the antidiabetic drug metformin on human esophageal cancer and conducted preclinical studies.
The research team elaborated on relevant scientific issues at various levels, including molecules, cells, holistic (animal models) and patient specimens. It was found that metformin can selectively inhibit the growth of esophageal squamous cell carcinoma cells, in addition to inducing apoptotic cell death and inhibiting cell proliferation, and also induce autophagy. By inhibiting autophagy at the drug or gene level, tumor cells can be made more sensitive to metformin-induced apoptotic death.
Metformin treatment inactivates the Stat3 pathway, particularly the Stat3-Bcl2-Beclin1 network signaling pathway, promotes crosstalk between apoptosis and autophagy, and forms a growth inhibition of metformin on tumors.
Source: Cell Death Dis, 2014, 5: e1088.
4. Metformin inhibits liver cancer
Professor Wang Hongyang, an academician of the Chinese Academy of Engineering, led a researcher at the Second Military Medical University and the Shanghai Jiaotong University School of Medicine to find out that metformin has an inhibitory effect on liver cancer. Related research papers were published in the form of cover articles in the journal Clinical Cancer Research, an international oncology journal.
The study of 273 cases of liver cancer patients found that the activity of protein kinase (AMPK) in liver cancer cells was reduced, and low levels of AMPK activity were associated with poor prognosis. Metformin activates AMPK in hepatoma cells, inhibits cell proliferation, and reduces tumorigenicity in vivo. Researchers have analyzed the molecular mechanism of this effect, namely that metformin exerts its role in inhibiting the activity of the transcription factor NF-KB signaling pathway by activating AMPK.
This study reveals that metformin has great potential for the treatment of hepatocellular carcinoma.
Source: Clin Cancer Res, 2013, 19(19): 5372-5380.
5. Metformin can significantly reduce the risk of kidney cancer in people with type 2 diabetes
A study on the effect of metformin on the risk of renal cell carcinoma in patients with type 2 diabetes included 171,753 patients with type 2 diabetes mellitus aged 40 years or older who were using or previously used metformin (metformin use group) and other A total of 75,499 patients with hypoglycemic drugs were used as a control group, and participants were followed up for 6 months.
The results of the study showed that 917 patients and 824 renal cancers occurred in the metformin use group and the control group during the follow-up period, and the incidence rates were 80.09/100,000 person-years and 90.30/100,000 person-years, respectively. Compared with the control group, metformin use group can significantly reduce the risk of kidney cancer (HR=0.279, 95% CI: 0.254～0.307); according to metformin use time is divided into <14.5 months, 14.5～45.8 months,>45.8 months In the three subgroups, the risk of renal cancer was HR=0.598 (95% CI: 0.535-0.668), 0.279 (95% CI: 0.243-0.321), and 0.104 (95% CI: 0.088-0.124). .
Subgroup analysis showed that the use of metformin reduced the risk of kidney cancer regardless of whether men and women were associated with other hypoglycemic agents.
Source: Eur J Cancer, 2016, 52:19-25.
People who were previously worried about severe kidney damage would develop a large accumulation of metformin in the body, which would increase the risk of lactic acidosis. However, a growing number of studies have found that in patients with type 2 diabetes who have mild to moderate renal impairment, metformin is associated with lower levels of urinary protein and serum creatinine compared with those who discontinue metformin. The trend means that kidney function has improved, which may be related to factors such as a significant decrease in blood glucose after metformin, decreased blood glucose fluctuations, and weight loss. These patients eventually prolonged their lifespan and improved their quality of life by adding metformin.
Metformin not only occupies an absolute “one brother” position in hypoglycemic drugs, but also has surprising effects in many other aspects, and may give us more surprises. Metformin can not only fight alone, but also cooperate with almost all other types of hypoglycemic drugs and achieve synergy of "1+1>2".
The status of metformin, the old drug, cannot be overtaken in the next 20 years, or even in 50 years.
In 1918, pharmacists discovered that terpenoids in plants reduced urine sugar and targeted the goat beans;
In 1922, Irish scientists successfully synthesized metformin for the first time;
In 1957, metformin patented by Bristol-Myers Squibb was first approved in France as a hypoglycemic drug for clinical use and was named "Gehua Zhi". In the next 50 years, metformin became the classic drug for the treatment of type 2 diabetes;
On December 29, 1994, metformin was approved for marketing by the US FDA.
In 1998, the UKPDS (UK Prospective Diabetes Study) milestoned the long-term benefits of metformin cardiovascular protection: “Metformin is the only hypoglycemic agent that reduces major vascular complications and reduces type 2 diabetes complications and mortality. ";
In 2002, the EU approved Gehua for the treatment of type 2 diabetes in children aged 10-16 years;
In 2005, IDF (International Diabetes Federation) evaluated metformin “is the cornerstone of drug treatment for type 2 diabetes”;
The clinical trials related to metformin are as follows
Metformin And Chloroquine in IDH1/2-mutated Solid Tumors;
Metformin in Non SmallCell Lung Cancer (NSCLC);
Study of Metformin With Simvastatin for Men With Prostate Carcinoma ;
Spironolactone Plus Metformin in Polycystic Ovary Syndrome;
A Study of Metformin With or Without Rapamycin as Maintenance Therapy After Induction Chemotherapy in Subjects With Pancreatic Cancer;
Neoadjuvant Letrozole Plus Metformin vs Letrozole Plus Placebo for ER-positive Postmenopausal Breast Cancer;
Metformin in Stage IV Lung Adenocarcinoma;
Impact of Pretreatment With Metformin on Colorectal Cancer Stem Cells (CCSC) and Related Pharmacodynamic Markers;
Metformin can actually fight aging and prolong life!
Metformin - "Shen medicine" is not a virtual name
Speaking of metformin, everyone will not be unfamiliar, but it is one of the most classic hypoglycemic agents, which has an irreplaceable role in the treatment of diabetes. It is not only the preferred oral hypoglycemic agent for many patients with type 2 diabetes, but also the only oral hypoglycemic agent that can be used in children with type 2 diabetes...
Moreover, hypoglycemic does not seem to be the full capacity of it. In recent years, more and more epidemiological and laboratory studies have shown that the therapeutic and preventive effects of metformin in various diseases are gradually being discovered. Reports show that metformin has potential therapeutic and preventive effects on various cancers such as lung cancer, gastric cancer, pancreatic cancer, breast cancer, ovarian cancer, endometrial cancer, and colorectal cancer.
Even more amazing is that metformin also has the effect of anti-aging and longevity. Metformin, like caloric restriction, prolongs the life of the organism, which has been confirmed in nematodes, rats and mice. In this way, metformin is called "Shen medicine" and "Xiandan"! On July 30, 2013, a study published in the journal Nature Communications showed that regular administration of small doses of metformin during the middle age promoted the health and lifespan of mice. In a study published in the journal Diabetes, Obesity and Metabolism in 2014, researchers at Cardiff University in the UK also found that long-term use of metformin can significantly prolong the lifespan of patients with type 2 diabetes, and they may live longer than non-diabetics. Longer, and the drug is also beneficial to the health of non-diabetics. The world's first clinical trial of "Metformin against aging" will begin in the US this winter.
The article comes from the web.
Lianyungang kllne chemical co., LTD. Is a research and development service company integrating research and development, production and sales. The company was founded in 2010, after seven years of rapid development, the company comprehensive strength, now has independent standard research/office space of 1200 square meters, equipped with advanced organic synthesis and analysis of testing equipment. Shanghai xianghui medical technology co., LTD., with high-end technology, high-quality products and careful service to meet the needs of customers, spare no effort to create the maximum value for users.
Lianyungang Klinechem Co., Ltd
Contact Person: Dr. John Liu
Address: Jingqi Road, Weiwu Road, Coastal Industrial Park, Guanyun County, Lianyungang City, Jiangsu Province