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
- Powerful Combination of Two Experimental Drugs Counteracts Osteoarthritis in Ratson January 27, 2020 at 11:44 am
A research team headed by scientists at the Salk Institute for Biological Studies has discovered that a combination of two molecules, alpha-KLOTHO (αKLOTHO) and TGF beta receptor 2 (TGFβR2), reverses ...
- Combination therapy of α -KLOTHO and TGFβR2 improves osteoarthritison January 22, 2020 at 7:19 am
A study has shown that a combination of α-KLOTHO and TGF β receptor 2 (TGFβR2) recovers cartilage in rats with osteoarthritis and could be a new therapy for humans. Researchers have identified that a ...
- Drug Combination May Reverse Osteoarthritison January 21, 2020 at 11:15 pm
New drug combination containing alpha-KLOTHO and TGF beta receptor 2 could prevent this wear and tear arthritis.’ Affecting 30 million adults, osteoarthritis is the most common joint disorder in the ...
- Could α-Klotho be a potential biomarker of stress?on July 23, 2019 at 5:00 pm
In a study published in the Journal of Investigative Medicine, researchers from Osaka University reported a unique association between stress and serum levels of α-Klotho (αKl). αKl was ...
- A Boost of Klotho Protein Level Has Therapeutic Potential in Amyotrophic Lateral Sclerosis (ALS), Also Known as Lou Gehrig's Diseaseon June 27, 2019 at 10:16 am
BOSTON, June 27, 2019 /PRNewswire/ -- In a paper published today, scientists report that increasing the levels of the naturally occurring Klotho protein reduces the neurological deficits and ...
- NGM Bio to Present New Data from Phase 1b Study of NGM313 at 79th Scientific Sessions of the American Diabetes Associationon June 5, 2019 at 12:00 am
NGM313 (MK-3655) is an investigational agonistic antibody that selectively activates the B-Klotho/FGFR1c receptor complex. The Phase 1b randomized, open-label, active-controlled parallel group ...
- UNITY and UCSF continue alpha-Klotho research collaboration that began in 2017on May 28, 2019 at 5:00 pm
29 mai 2019 16h05 HE | Source : Unity Biotechnology, Inc. UNITY Biotechnology, Inc. Investors Peter Rahmer Endurance Advisors Media Canale Communications Jason Spark UCSF Media Laura Kurtzman ...
- Is Klotho’s Partner FGF23 a Cognition Protein?on March 20, 2019 at 1:12 pm
The longevity gene klotho keeps memory keen, but how? New research raises the possibility that it might influence cognition through its signaling partners FGF23 and the fibroblast growth factor (FGF) ...
- Klotho suppresses colorectal cancer through modulation of the unfolded protein responseon September 19, 2018 at 5:39 am
Klotho is an anti-aging transmembrane protein, which can be shed and function as a hormone. Accumulating data indicate klotho as a tumor suppressor in a wide array of malignancies and indicate the ...
via Bing News