Delivery of recombinant klotho, or fragments of klotho, has been an area of interest for the research community. Upregulation of klotho expression has been shown to extend life in mice, and klotho appears to be involved in regulation of tissue aging in a number of different organs. This may all be the consequence of the effects of klotho on declining kidney function with age, given discoveries to date relating to the relationship between klotho, kidney function, and cognitive aging, but investigations are still ongoing, and other more direct connections may yet be found.
Researchers characterised and compared changes in the structure, function, and gene activity in skeletal muscle across the lifespan in mice. They grouped mice into four age categories - young, middle-aged, old and oldest-old - and looked at muscle weight, type of muscle fibers, whether the muscles had accumulated fat, and skeletal muscle function. Although old mice displayed mild sarcopenia, the common clinical features of sarcopenia were only present in the oldest-old mice. Next, they looked at changes in muscle gene activity and found a progressive disruption in genes known to be associated with the hallmarks of aging from the young to the oldest-old mice.
Next, they looked at whether administering Klotho to mice would have beneficial effects on the muscle healing after injury. They found that applying Klotho after muscle injury reduced scarring and increased structures associated with force production in the animals. Injured mice that received Klotho also had better muscle function - such as muscle twitch and force production - and their whole-body endurance improved two-fold.
Finally, the team looked at whether giving the mice Klotho could reverse age-related declines in muscle quality and function. They found that Klotho administration led to some improvements in the old mice: force production was improved by 17% and endurance when supporting whole body weight was 60% greater compared to mice without treatment. But this was only seen in the old mice, and not in the oldest-old animals. Further investigation showed that Klotho affected genes associated with the hallmarks of aging in all age groups, but that the oldest-old mice showed a dysregulated gene response.