Small-molecule drug simultaneously rescues aged brain and muscle tissue

Written by Alexandra Thompson

Researchers at the University of California, Berkeley have identified a single molecule that may lead to generation of a drug that would help rejuvenate both the human body and mind.

Aging is partly attributed to inhibitory chemicals in adult stem cells’ environments causing them to fail to produce replacement cells for damaged cells, and therefore being unable to repair the body’s tissues. Some of these inhibitory chemicals have been dumped there by the immune system as a result of chronic, low-level inflammation, which is also a hallmark of aging.

The growth factor TGF-beta1 has previously been shown by associate professor of bioengineering Irina Conboy (University of California, Berkeley, CA, USA) to reduce various types of stem cells ability to renew tissue. “Based on our earlier papers, the TGF-beta1 pathway seemed to be one of the main culprits in multi-tissue aging,” stated Conboy. “That one protein, when upregulated, ages multiple stem cells in distinct organs, such as the brain, pancreas, heart and muscle.”

Now, a University of California, Berkeley research team have identified a drug interferes with the activity of TGF-beta1, thereby generating increased stem cell activity. “This is really the first demonstration that we can find a drug that makes the key TGF-beta1 pathway, which is elevated by aging, behave younger, thereby rejuvenating multiple organ systems,” Conby explains.

The team injected a chemical known to block the TGF-beta1 receptor and therefore reduce the effect of TGF-beta1 into the blood of an animal model. This small molecule, an Alk5 kinase inhibitor, successfully renewed stem cell function in both brain and muscle tissue, potentially making it stronger and cleverer.

The research was published in the journal Oncotarget. Co-author David Schaffer, director of the Berkeley Stem Cell Center and a professor of chemical and biomolecular engineering, states: “We established that you can use a single small molecule to rescue essential function in not only aged brain tissue but aged muscle… That is good news, because if every tissue had a different molecular mechanism for aging, we wouldn’t be able to have a single intervention that rescues the function of multiple tissues.”

The researche team noted that since other biochemical cues also regulate adult stem cell activity, this is simply a first step toward a therapy. Schaffer and Conboy’s research groups are now collaborating to try to modulate of two key biochemical regulators, in the hope this multi-pronged approach might lead to safe restoration of stem cell responses in multiple aged and pathological tissues.

“The challenge ahead is to carefully retune the various signaling pathways in the stem cell environment, using a small number of chemicals, so that we end up recalibrating the environment to be youth-like,” Conboy said. “Dosage is going to be the key to rejuvenating the stem cell environment.”

The research team are members of a consortium of faculty who study aging within the California Institute for Quantitative Biosciences (QB3). The mission of the QB3 is to stimulate innovative life science to keep us healthy, sustain our environment and grow the economy, via promotion of interdisciplinary research and partnerships, providing research, education programs, etc.