One of the downsides to getting older is that skeletal muscle loses its ability to heal after injury. New research from the University of Pittsburgh implicates the so-called “longevity protein” Klotho, both as culprit and therapeutic target.
The paper, published this week in Nature Communications, showed that, in young animals, Klotho expression soars after a muscle injury, whereas in old animals, it remains flat. By raising Klotho levels in old animals, or by mitigating downstream effects of Klotho deficiency, the researchers could restore muscle regeneration after injury.
“We found that we were able to rescue, at least in part, the regenerative defect of aged skeletal muscle,” said lead author Fabrisia Ambrosio, Ph.D., director of rehabilitation for UPMC International, associate professor of physical medicine and rehabilitation at Pitt, and core faculty at the McGowan Institute of Regenerative Medicine. “We saw functional levels of muscle regeneration in old animals that paralleled those of their young counterparts, suggesting that this could potentially be a therapeutic option down the road.”
Suspecting that Klotho acts through mitochondria dysfunction, the researchers gave Klotho-deficient animals a mitochondria-targeting drug called SS-31, which currently is in phase III clinical trials. Treated animals grew more new muscle tissue at the site of injury compared to untreated controls, and their strength after recovery rivaled that of genetically normal mice.
Similarly, injecting Klotho into older animals a few days after injury resulted in greater muscle mass and better functional recovery than their saline-treated counterparts. Normal, healthy mice did not benefit from SS-31 after injury.
Clinically, these findings could translate to older adults who either sustained a muscle injury or underwent muscle-damaging surgery. Giving them Klotho at the appropriate timepoint could boost their muscle regeneration and lead to a more complete recovery.
Ambrosio cautions that the timing, dosage and route of administration will require future research.
“If you just bombard the muscle with Klotho, we do not expect to observe any functional benefit,” Ambrosio said. “We’ve found that mimicking the timing profile we see in young animals seems to be critical. We think that this gives some insight into the therapeutic window.”
The Latest on: Klotho
via Google News
The Latest on: Klotho
- $23.11 Million in Sales Expected for NGM Biopharmaceuticals, Inc. (NASDAQ:NGM) This Quarteron March 1, 2021 at 8:17 am
Wall Street analysts forecast that NGM Biopharmaceuticals, Inc. (NASDAQ:NGM) will report $23.11 million in sales for the current fiscal quarter, Zacks reports. Four analysts have issued estimates for ...
- SG Americas Securities LLC Purchases 16,675 Shares of NGM Biopharmaceuticals, Inc. (NASDAQ:NGM)on February 26, 2021 at 2:58 am
SG Americas Securities LLC raised its position in NGM Biopharmaceuticals, Inc. (NASDAQ:NGM) by 142.5% in the 4th quarter, according to its most recent Form 13F filing with the SEC. The institutional ...
- Kidney and epigenetic mechanisms of salt-sensitive hypertensionon February 24, 2021 at 3:20 am
In this Review, the authors discuss the renal mechanism of salt-sensitive hypertension induced by malnutrition during pregnancy, obesity in adult life and ageing. They also describe the epigenetic ...
- Mental Health and Psychiatric Nursing Newson February 13, 2021 at 4:00 pm
Medscape Medical News, September 30, 2015 ANA Klotho Levels Linked to Enhanced Cognition Though preliminary, findings showing remarkable cognitive improvement in humans and mice with higher levels ...
- University of São Paulo: Discovery involving proteins reinforces the need to do biomedical research with both sexeson February 12, 2021 at 1:24 am
ANDa study carried out at USP’s Institute of Biomedical Sciences (ICB) with male and female mice revealed differences as each sex expresses two proteins important to the central nervous ...
- Investigating a Stress Protein's Relation to Heart Failureon February 2, 2021 at 3:28 am
Treating heart failure has proven problematic, as few therapeutic targets are known. Alpha-Klotho (αKl) is a protein believed to be related to aging in animals. Normally bound to a cellular membrane ...
- Anti-aging gene helps reduce hypertensionon January 28, 2021 at 8:58 am
Scientists from University of Oklahoma Health Sciences Centre have found that an anti-aging gene might play a critical role in regulation of high blood pressure. Persistent high blood pressure is ...
- Aging, the Aging Lung, and Senile Emphysema Are Differenton March 9, 2018 at 5:13 pm
Second, gene regulation of aging is complex. The master gene of aging has not been determined, although the Klotho gene is a candidate (6). Klotho gene–deficient mice develop the airspace enlargement ...
- 2015 - Dena Dubalon June 10, 2016 at 1:46 pm
Using multiple research methodological approaches, her lab is investigating how a hormone, knows as Klotho, enhances healthy longevity - living longer and with improved cognition. SCU student Naimi ...
via Bing News