Chinese scientists say they have developed a potential longevity drug that induces pseudo-starvation in cells to activate an energy-regulating enzyme and reduce fat storage.
The team, led by researchers from Xiamen University, said the chemical compound has also been shown to extend life and health span, or the period spent in good health, in worms and mice, adding that it is a potential therapy for treating metabolic disorders such as diabetes and fatty liver disease.
Lead author Professor Lin Shengcai, a metabolic biologist at Xiamen University, said the drug was developed based on the mechanism of an ancient Chinese fasting practice called bigu, or “avoidance of grains”.
This involved long-term abstinence from the “five grains” – varieties of rice, wheat and millet, hemp seeds and soybeans – for increased spirituality, health and longevity. Today it is better known as fasting or intermittent fasting.
“Our medicine mimics the God-given path for bigu and is designed for longevity. We found the key to extending life in caloric restriction and fasting,” said the scientist from the Chinese Academy of Sciences.
“I am extremely excited about my drug, the first to be developed from scratch, from mechanism, pathway, target to clinical benefits, in China,” Lin said, adding that the team hopes to test the product in human clinical trials in a few years.
The team, which also includes researchers from the Sixth People’s Hospital of Shanghai, Tsinghua University and CAS’s Dalian Institute of Chemical Physics, published its findings in the peer-reviewed journal Nature Metabolism on October 10.
They found that the drug aldometanib extended life and healthy life expectancy in small roundworms from an average age of 18 to 26 days and mice by at least 7.5 percent.
It also lowered glucose in mice without causing the level to drop too low and alleviated fatty liver and non-alcoholic steatohepatitis, an aggressive form of fatty liver disease, in obese rodents, according to the study.
The team also observed a significant decrease in body weight, fat mass and body fat composition in mice treated with aldometanib for one month, while their lean mass did not change.
Meanwhile, running distance, duration, and grip strength were significantly increased in treated mice at 1 year of age.
Lin said the drug — which they say controls weight, regulates blood sugar levels, relieves inflammation, increases metabolic rate and has a rejuvenating effect — could potentially benefit people with diabetes, fatty liver disease and obesity, as well as those who hope to live long and healthy lives.
The energy-sensing enzyme AMPK is found in every eukaryotic cell or those with a nucleus and is naturally activated when glucose availability becomes low.
“It’s a monitoring and alarm system that goes off when there’s a chance that the energy in the body is going to drop — but before the drop,” Lin said.
To activate AMPK, the Chinese team developed the new drug to mimic glucose starvation at the cellular level. According to Lin, it works by blocking a metabolic derivative of glucose from binding to aldolase, an enzyme that breaks down sugars to produce energy.
“Aldolase is like scissors. When there is no cloth to cut, it feels like the family is poor and AMPK is activated,” Lin said.
“It’s also like a child looking at its mother’s face, the glucose derivative, to determine if it’s going to be fed, rather than looking for food or glucose itself in her pockets.”
Because the drug mimics the state of starvation in the cells without changes in energy levels in the body, the feeling of hunger does not occur, Lin said.
Compared to the new drug, metformin — an existing drug also known to activate AMPK — had a limited effect in lowering glucose, according to the study.
Metformin, a common treatment for type 2 diabetes, can target the liver, kidney and intestine, but not skeletal muscle, an important tissue for lowering glucose because of its large contribution to body mass.
This article was first published in the South China Morning Post.