Why IBM Muscles Struggle to Make Energy: New Mayo Clinic Study Finds Widespread Mitochondrial Damage
Fatigue is one of the most common — and most under-appreciated — symptoms of IBM. It is also one of the hardest to explain: blood tests often look normal, and the weakness seems out of proportion to the inflammation doctors can see. A new study from Mayo Clinic, published August 2, 2026 in the journal Brain, offers a compelling explanation: the tiny power plants inside muscle cells — the mitochondria — are failing in multiple ways at once.
What the Researchers Did
Researchers compared muscle tissue from 67 people with IBM and 45 healthy controls. They used a wide battery of techniques, from measuring the output of energy-producing proteins to directly measuring how much oxygen muscle fibers consume — the most direct way to gauge whether mitochondria are actually making energy. They also looked closely at differences between men and women, because IBM affects the two slightly differently.
First, a quick primer: cells make most of their energy inside mitochondria, using a chain of five protein complexes (numbered I through V). This chain is like a production line — if any step is slow, the whole line slows down, and the cell gets less energy from the same amount of fuel.
What They Found
IBM muscle produced substantially less energy than healthy muscle, and the mitochondria that remained were less efficient — they leaked energy instead of capturing it for the muscles. This helps explain a puzzle that has frustrated doctors and patients for years: why IBM patients can have such profound fatigue even when routine tests look unremarkable.
The study also found lower levels of mitochondrial DNA in IBM muscle, reduced output of energy-chain proteins, and a weakened "recycling" system (called mitophagy) that normally clears out damaged mitochondria. All three problems were linked to one another and to the severity of the disease — suggesting they are connected parts of the same disease process rather than separate issues.
One of the most interesting findings was the difference between men and women. A key part of the energy chain (Complex I) was reduced mainly in women, and in women alone, energy-chain dysfunction tracked with how long a patient had been living with the disease and how severe it was. Men showed different patterns of impaired energy production. The authors say future treatments may need to account for these sex-specific differences — an early, hypothesis-generating observation, not something patients should act on yet.
What This Means for IBM Patients
For patients, the takeaway is this: when you feel exhausted, it is not "all in your head," nor is it simply about inflammation. The machinery that makes energy in your muscles is genuinely damaged, in measurable ways. Understanding exactly how is the first step toward therapies that might improve muscle energy — and it gives researchers a new way to measure whether a treatment is working.
This is a biology study, not a treatment trial, so it does not change treatment today. But it adds to a growing picture that mitochondria deserve serious attention in IBM research. It comes from the journal Brain, one of the most respected neurology publications, and from a Mayo Clinic team with deep experience studying IBM. (Note: an earlier version of this work circulated as a preprint in February 2026; the final peer-reviewed version was published in Brain in August 2026.)
Source
• Shammas I, Iaali H, Watzlawik JO, et al. "Multilevel impairment of mitochondrial respiration in inclusion body myositis." Brain. 2026 Aug 2. doi: 10.1093/brain/awag269. PMID: 42542327.
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