媒体联络:
朱莉·基弗
Director, 研究 Communications, University of Utah Health
电子邮件: 朱莉.Kiefer@hsc.犹他州.edu
You might not think of 糖尿病 when you think of muscle function. But a common 糖尿病 drug that regulates blood sugar can also prevent muscle atrophy and muscular fibrosis—which can help the elderly bounce back faster from injury or illness.
University of Utah Health researchers have discovered that Metformin, a common drug that’s been used in 糖尿病 treatment for more than half a century, has surprising applications on a cellular level. It can target “zombie-like cells,” called senescent cells, which impact muscle function. Senescent cells secrete factors associated with inflammation that may underlie fibrotic tissue, 硬化组织硬化或结疤. Metformin also reduces muscle atrophy. 他们的研究结果发表在 衰老细胞.
“We’re interested in clinical application of this research,” says 弥迦书德拉蒙德博士.D., senior author of the study and professor of physical therapy and athletic training at the College of Health. “For example, knee surgeries in the elderly are notoriously hard to recover from. If we give a Metformin-type agent during the recovery period, could we help the muscles get back to normal faster?”
恢复肌肉活力
随着成年人年龄的增长, 他们更有可能摔倒, 住院, 或者患上慢性疾病, and muscle disuse increases these risks. The research team wanted to find a therapeutic solution that could properly target both disuse atrophy and muscle recovery.
There’s an optimal level of senescent cells that are beneficial, no matter your age. 在年轻, 健康的人, short-term senescence is required for a proper recovery from injury, and completely blocking the senescent effect impedes the body’s efforts to heal. 通常, a younger person can bounce back more easily after muscle disuse without the use of an intervention such as Metformin.
“In the case of aging, we know that there’s immune dysfunction,” says Drummond. “As you get older, it becomes harder for your body to clear senescent cells and they accumulate. That’s one reason recovery is much slower for the elderly after periods of disuse.”
Metformin’s anti-senescent properties have been demonstrated through pre-clinical studies. To test the intervention in humans, the team recruited 20 healthy male and female older adults for a multi-week study. They had participants undergo a muscle biopsy and MRI before the intervention, which involved five days of bed rest. One group of 10 received Metformin and the other 10 received placebo pills during a two-week run-in period, then each group continued the placebo or Metformin treatment during bed rest.
As you get older, it becomes harder for your body to clear senescent cells and they accumulate. That’s one reason recovery is much slower for the elderly after periods of disuse.
After the bed rest, participants received another muscle biopsy and MRI, then ceased treatments. All patients completed a seven-day re-ambulation period followed by a final muscle biopsy.
“We saw two things in our study,” Drummond says. “When participants took Metformin during a bed rest, they had less muscle atrophy. During the recovery period, their muscles also had less fibrosis or excessive collagen. That build-up can make it harder for the muscle to properly function.”
将这些结果与衰老联系起来, the research team examined muscle biopsies from study participants. They found that the participants who took Metformin had fewer markers of cellular senescence.
“This is the first paper that has made the direct connection between a therapy targeting cellular senescence and improved muscle recovery following disuse in aging,” says lead author Jonathan Petrocelli, Ph.D. He explains that metformin helps muscle cells better remodel and repair tissue during periods of recovery after inactivity.
“Our real goal is to have patients maintain their muscle mass and function as they age, because atrophy and weakness are some of the strongest predictors of disease development and death,他说.
Drummond’s team is following up on these findings by examining combining the drug with leucine, an amino acid that promotes growth and could accelerate recovery even further. They’ve already demonstrated the potency of this combination in preclinical animal studies.
“二甲双胍很便宜, 有效且安全, so it’s exciting to see that we can use it to accelerate recovery for older individuals,德拉蒙德补充道。.
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“废用性肌肉纤维化, cellular senescence and senescence-associated secretory phenotype in older adults are alleviated during re-ambulation with metformin pre-treatment" was co-funded by the National Institutes of Health and University of Utah Center on Aging.
In addition to Drummond and Petrocelli, the study’s co-authors are Alec I. 我是内奥米·麦肯齐. 保罗·T·德哈特著. 雷迪，齐亚德·S. 亚历山大·马马萨尼. 凯蒂·基布尔. 卡普特，马修·P. 马修·T. 罗迪纳，罗宾·L. 马库斯，科琳·K. 嗯，威廉·L. Holland, Katsuhiko Funai and Christopher S. 弗莱.
——莎拉·谢贝克著