Finding compounds to reduce jet lag

Researchers investigated existing drugs for molecules that affect circadian rhythms and found a known anti-aging supplement reduced jet lag in mice.

Studies show that about 5% of existing drugs may have an effect on circadian rhythms.

A hormone used as a common anti-aging supplement shortened the circadian cycle and significantly reduced jet lag symptoms when fed to mice, according to research led by Nagoya University’s Institute of Transformative Bio-Molecules.

Jet lag is caused by a mismatch between external time cues and the internal biological clock. This clock plays an important role in regulating sleep/wake cycles, hormone secretion and metabolism. Frequent travel and shift work can chronically disrupt humans’ 24-hour rhythm, leading to sleep disorders, obesity and an increased risk of cancer in the long term.

There are no medications currently available on the market to treat jet lag, and developing new drugs is expensive and time consuming. So, ITbM animal biologist Takashi Yoshimura, cell biologist Katherine Tamai, and colleagues took a ‘drug repurposing’ approach, screening over 1,000 compounds, including those approved by food and drug regulatory authorities in the US, Europe and Asia, and others under clinical trial, to search for already-existing drugs that can regulate the circadian rhythm in mammals.

They found 46 compounds that lengthened the circadian period and 13 that shortened it. These compounds contained bioactive molecules used as anticancer, antibacterial, and contraceptive agents; hormones; vitamins; and drugs used to treat diseases related to the central nervous system, digestive system, heart and skin.

Yoshimura and his group looked further into the circadian period-shortening compounds that could fast forward the circadian clock and relieve jet lag symptoms when travelling from west to east. They found that the steroid hormone dehydroepiandrosterone (DHEA), which is commercially available as an anti-aging supplement in the US, shortened the period of the circadian clock in cultured human cells in a dose-dependent manner.

Mice were then exposed to conditions that advanced the light-dark cycle by six hours, similar to a trip from Japan to Alaska. Jet-lagged mice that were fed DHEA appeared to recover and adapt to the new time zone faster than mice that were fed normal food.

Further investigations are required to evaluate the effectiveness of DHEA for the treatment of jet lag in humans.

“We are currently expanding our chemical libraries and are now screening food additives and natural products to find other compounds that can regulate the circadian clock in humans,” says Yoshimura. “We hope to develop and deliver new and safe compounds that can be taken orally to cure jet lag.”

For more information, contact:

Professor Takashi Yoshimura
Institute of Transformative Bio-Molecules (WPI-ITbM)
Nagoya University
E-mail: [email protected]

Dr T. Katherine Tamai
Institute of Transformative Bio-Molecules (WPI-ITbM)
Nagoya University
E-mail: [email protected]