A team led by W. David Arnold of the University of Missouri and Brian C. Clark of Ohio University ran this test on ten people aged 83 to 96, mean age 85.9. Nine had clinically meaningful weakness of the leg extensors. They were compared with eight adults aged 20 to 45. In the weak older adults mean jitter was about 250 per cent higher, and nearly all showed blocking. The worse the signal stalled, the weaker the leg. Strength per unit of muscle volume was 44 per cent lower.
Sarcopenia is the loss of muscle strength and mass with age. The usual focus is the shrinking muscle. This work looks instead at the neuromuscular junction, where the nerve hands its signal to the fibre. The paper went online in The Journal of Clinical Investigation on 9 July 2026, in the 1 September issue. The university's press release followed on 24 September.
The rest of the work is in animals. Mice aged 26 to 27 months and Wistar rats aged 22 to 23 months showed the same transmission failure. According to the authors, the fault does not lie with acetylcholine, the nerve's chemical messenger. It lies in the fibre, which responds less to the signal right beside the junction. There, in humans and rodents alike, immunohistochemistry found less NaV1.4, the sodium channel specific to skeletal muscle. The human evidence comes from three biopsies per age group, taken from the dorsal interosseous muscles of the hand during reconstructive surgery.
To test the link, the authors blocked that channel in adult rats with μ-conotoxin GIIIB, a cone-snail toxin that shuts muscle NaV1.4. The young rats then showed the same jitter and the same blocking as old ones.

Then the drug. ClC-1 is a chloride channel that keeps the fibre at rest and damps its excitability. Inhibiting it makes the fibre readier to fire. In 20-month-old rats the compound NMD1226, given by mouth at 60 milligrams per kilogram twice a day for seven days, raised stimulated muscle force by 14.4 per cent. With vehicle alone force fell by 3.6 per cent. Grip strength rose 11.2 per cent with the drug and fell 9.7 per cent without it. One day after dosing stopped, grip was back to control values. In old mice a second compound, NMD653, cut jitter from 20.4 to 13.7 microseconds. The groups are small, in one experiment five treated animals and four controls.
One detail in the paper deserves attention. At the start, the rats assigned to the drug had a weaker grip, 1.84 grams of force per gram of body weight against 2.13. A group that starts lower has more room to climb, and part of the gain may come from that.

NMD1226 and NMD653 belong to NMD Pharma, a Danish firm based in Aarhus, which has ten employees among the authors. NMD Pharma is listed among the funders alongside two National Institutes of Health grants. The press release mentions the collaboration with the company and an animal model. It does not say how many older people were tested, nor that the drug trial lasted a week.
The authors state their limitations. The human sample is small. Changes in NaV1.4 vary from muscle to muscle and from species to species. Slow-twitch human muscle was barely examined. The voluntary-strength study lasted seven days. The journal received the paper on 27 January 2025 and accepted it on 2 July 2026, seventeen months later. The mechanism is new and plausible. The therapy, for now, exists in rats.

Wistar rats aged 20 months treated for seven days with NMD1226, an inhibitor of the ClC-1 chloride channel, or with vehicle alone. Percentage change in stimulated muscle force and in grip strength from baseline. In-house chart. Chart produced by ScienceOnline from data in Arnold W. D. et al., The Journal of Clinical Investigation 2026, doi 10.1172/JCI190646.

References
Arnold W. D., Morgen J. J., Thomasen P. B. et al., “Neuromuscular junction failure in sarcopenia is linked to NaV1.4 loss and reversed by ClC-1 inhibition”, The Journal of Clinical Investigation, 136, 17, e190646, online 9 July 2026, issue of 1 September 2026, CC BY 4.0 licence. doi: 10.1172/JCI190646
University of Missouri-Columbia, press release, re-run by ScienceDaily as “Aging Muscles May Be Losing Strength for a Reason Scientists Missed”, 24 September 2026 (used only for comparison with the paper).