Drug Candidate Seems To Wake Up Aging Brains and Muscles

Anti-Aging  

Researchers have discovered that a small-molecule drug simultaneously perks up old stem cells in the brains and muscles of mice, a finding that could lead to drug interventions for humans that would make aging tissues throughout the body act young again.

Researchers at UC Berkeley have discovered a small-molecule drug that may be the fountain of youth for aging brains and muscles. In mouse models the drug is working wonders and they hope their findings will lead to a drug that does the same thing for humans.

"We established that you can use a single small molecule to rescue essential function in not only aged brain tissue but aged muscle."

“We established that you can use a single small molecule to rescue essential function in not only aged brain tissue but aged muscle,” said co-author David Schaffer, director of the Berkeley Stem Cell Center and a professor of chemical and biomolecular engineering. “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.”

Their findings were published in the journal Oncotarget.

In mice, as in humans, stem cell function declines with age. The drug interferes with the growth factor, TGF-beta1 that keeps those stem cells from regenerating.

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By inhibiting TGF-beta1, researchers were able to enhance neurogenesis and muscle regeneration in 24-month-old laboratory mice, the age equivalent of 80-year-old humans.

If humans were to respond the same way, age-related degeneration such as loss of agility, mobility, memory, learning and independence could be treatable.

The small-molecule drug is already being used in trials as an anticancer agent. Researchers say it holds a lot of promise when when used on stem cells, because it can regenerate both the mind and the body.

Images of cells in the brain’s
hippocampus show that the growth
 factor TGF-beta1 (stained red)
 is barely present in young tissue
 but ubiquitous in old tissue,
where it suppresses stem
cell regeneration and
contributes to aging.

“You can simultaneously improve tissue repair and maintenance repair in completely different organs, muscle and brain,” said UC scientist Irina Conboy.

“Based on our earlier papers, the TGF-beta1 pathway seemed to be one of the main culprits in multi-tissue aging,” said Conboy, an associate professor of bioengineering. “That one protein, when upregulated, ages multiple stem cells in distinct organs, such as the brain, pancreas, heart and muscle. 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.”

She and her colleagues caution this new drug “is only a first step toward a therapy, since other biochemical cues also regulate adult stem cell activity.” They noted that this is only a first step toward a therapy, since other biochemical cues also regulate adult stem cell activity. Schaffer and Conboy’s research groups are now collaborating on a multi-pronged approach in which modulation of two key biochemical regulators 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.”


SOURCE  Berkeley Research

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