Category
Mitochondrial health
19 plain-language articles on mitochondrial health — the physiology, the compounds, and what the evidence actually shows.
19 articles
AMPK — the cellular energy sensor and why metformin became a longevity drugMetformin has been prescribed to people with type 2 diabetes since the 1950s in Europe and since 1995 in the United States. It is among the most prescribed drugs in the world, with a safety profile that decades of clinical use have established as genuinely good. For most of that time, nobody fully understood how it worked. The pharmacological mechanism — what it was actually doing in the cell to lower blood glucose — was the subject of debate for more than forty years. The explanation, when it arrived in the early 2000s, turned out to be more interesting than a diabetes mechanism. It pointed at a kinase that sits at the center of cellular energy sensing, and through that kinase it connected metformin to a biology that reaches from mitochondria to mTOR to lifespan.11 min readThe chronic fatigue that isn't a diagnosis — the categories under the symptomYour labs came back normal. Thyroid, CBC, metabolic panel — all within range. Your doctor looked at the results, looked at you, and said the thing that has become the most demoralizing sentence in modern medicine: everything looks fine. You nodded. You drove home. You got into bed at 3 p.m. not because you were lazy but because your body had nothing left, and "everything looks fine" didn't explain why or offer any path forward.9 min readElamipretide / Stegazo — the FDA approval for Barth syndrome and what it signalsThe boy is maybe three years old and smaller than he should be. He tires quickly. His heart is enlarged on the echocardiogram — a dilated cardiomyopathy that the pediatric cardiologist has seen before in adults but rarely in a child this young. Blood work comes back with abnormally low neutrophil counts, which means infections will be harder to fight. His muscles are weak in ways that developmental milestones can't fully capture until he starts school and the gap becomes visible to everyone. The cause is a mutation on the X chromosome that his mother carried without knowing, and there is, when his family sits with the geneticist, no approved treatment to discuss. The name of what he has is Barth syndrome.8 min readWhat people are reporting about HumaninThis article summarizes experiences reported in public online communities including Reddit, longevity forums, and discussion boards. We are not advocating human use of any compound discussed here. Many of the peptides discussed are not FDA-approved for the uses described, and some are explicitly not approved for human or veterinary use. What follows is a synthesis of what people have reported, presented to give readers context on the public conversation — not as guidance, not as evidence of safety or efficacy, and not as a recommendation. Decisions about any compound should be made with a qualified prescribing provider after a full medical evaluation.8 min readHumanin — the mitochondrial peptide that protects neuronsIn 2001, in a laboratory in Tokyo, a researcher named Yuichi Hashimoto was trying to understand why some neurons survive exposure to amyloid-beta and some don't. Alzheimer's disease research at that point was already deeply invested in the amyloid hypothesis — the idea that the accumulation of amyloid-beta peptide fragments is the initiating event in the disease — but the mechanism of neuronal death was still being worked out. Hashimoto's group was screening a library of expressed sequences from the brain tissue of Alzheimer's patients, looking for something that could explain or counteract the toxicity. What they found was not what they were looking for.8 min readMitochondrial biogenesis — how cells build more power plants, and why it fades with ageMitochondria were not always part of us. The leading account of their origin, championed and made rigorous by the biologist Lynn Margulis in the late 1960s against considerable resistance, is that more than a billion years ago a free-living bacterium was engulfed by a larger cell and, instead of being digested, struck a bargain. The bacterium supplied energy; the host supplied shelter and raw materials. Over deep time the guest became a permanent resident, surrendering most of its genome to the host nucleus but keeping a small loop of its own DNA — which mitochondria carry to this day. This endosymbiotic event is arguably the most consequential merger in the history of life, because the energy it unlocked made complex, large-celled organisms possible. Every breath you take feeds these descendants of an ancient bacterium, and the question of how a cell decides to build more of them sits at the center of modern metabolic and longevity science.8 min readMitochondrial DNA — your second genome and why it matters for agingMost people learn it once in high school biology and never return to it: mitochondria have their own DNA. The fact gets filed away alongside the powerhouse-of-the-cell mnemonic and mostly stays there, which is a pity. Because the implications of that second genome — separate from the nuclear DNA in your chromosomes, inherited through an entirely different pathway, subject to its own distinct vulnerabilities — turn out to be one of the more important threads running through the biology of aging.7 min readNAD+ vs MOTS-c vs SS-31 vs Humanin — the mitochondrial peptide stack, decodedYou got your labs back and your biological age came out higher than your chronological age. Or the fatigue is real — not the kind that coffee fixes, not the kind that a good night's sleep fully resolves — a deeper, structural tiredness that has started to feel like a baseline rather than a symptom. Or you've been researching longevity seriously and you've arrived at the mitochondria, because the research keeps pointing there: cellular energy, oxidative stress, the gradual degradation of the organelles that power everything else. You've encountered four names being discussed — NAD+, MOTS-c, SS-31, Humanin — and you want to understand what each actually does, why they're being discussed together, and whether the combination logic holds up.7 min readWhat people are reporting about MOTS-cThis article summarizes experiences reported in public online communities including Reddit, longevity forums, and discussion boards. We are not advocating human use of any compound discussed here. Many of the peptides discussed are not FDA-approved for the uses described, and some are explicitly not approved for human or veterinary use. What follows is a synthesis of what people have reported, presented to give readers context on the public conversation — not as guidance, not as evidence of safety or efficacy, and not as a recommendation. Decisions about any compound should be made with a qualified prescribing provider after a full medical evaluation.7 min readMOTS-c in longevity stacks — what's being exploredThe longevity protocol world has a stacking problem. Not a problem in the sense that stacking is necessarily wrong — combining compounds that address different mechanisms is conceptually sound in medicine — but a problem in the sense that the reasoning often runs backward. The aspiration comes first. The compounds follow. The mechanism gets retrofitted to justify what was already going to happen. When you're dealing with compounds that have thin human evidence and strong preclinical data, this pattern matters enormously, because it's the difference between a rationally assembled protocol and an expensive bet dressed up in biological language.7 min readMOTS-c in plain English — mitochondrial-derived peptides explainedYour mitochondria are not quiet. They're not just burning fuel and staying out of the way. They're running a continuous metabolic read on the cell's energy state and broadcasting updates — and those updates, it turns out, include peptides that circulate through the body and communicate with tissues that have nothing to do with where the mitochondria physically sit. MOTS-c is one of those peptides. Understanding what it actually does requires starting with what the cell does when energy runs low.8 min readNAD+ and CD38 — why supplementing alone might not be enoughYou start taking NMN. Your NAD+ levels come up, at least on a blood test. Three months later, maybe six, the effect seems to blunt. You're still taking it, the dose hasn't changed, but something about the initial lift has flattened. Maybe you increase the dose. Maybe it helps. Maybe it doesn't. You've entered a conversation that the supplement marketing doesn't prepare you for: that raising NAD+ levels is not just a question of what you put in, but of what's consuming it on the other end — and that consumption is running faster as you age.8 min readNAD+ in cognitive function and neuroprotectionYou notice it around mid-morning, maybe an hour or two after waking. The thoughts aren't quite connecting the way they used to. Words that were automatic are now effortful, just slightly — not the dramatic forgetting of a medical event, just a very quiet dimming. You'd dismiss it as tiredness or age if it weren't so consistent, if it weren't there even on the days when you slept well and ate well and did everything right. The cognitive baseline has shifted and the shift happened so gradually that you can't point to when it started. You just know it doesn't feel like before.8 min readWhat people are reporting about NAD+ infusionsThis article summarizes experiences reported in public online communities including Reddit, longevity forums, and discussion boards. We are not advocating human use of any compound discussed here. Many of the peptides discussed are not FDA-approved for the uses described, and some are explicitly not approved for human or veterinary use. What follows is a synthesis of what people have reported, presented to give readers context on the public conversation — not as guidance, not as evidence of safety or efficacy, and not as a recommendation. Decisions about any compound should be made with a qualified prescribing provider after a full medical evaluation.8 min readNAD+ IV vs subcutaneous vs oral — what bioavailability research suggestsYou've read the research, or at least enough of it. You understand that NAD+ declines with age, that sirtuins need it, that mitochondrial energy metabolism depends on it. You've decided the conversation is worth having with your prescribing provider. And then you hit the question that the popular articles tend to gloss over: take it how, exactly? A capsule? A drip? A weekly injection? The delivery route for NAD+ is not a minor implementation detail. For this particular molecule, it might be the most consequential decision in the entire protocol.8 min readNAD+ vs NMN vs NR — the precursor conversationYou're standing in the supplement aisle — or the online equivalent of it, scrolling through a longevity stack that someone recommended on a podcast — and there are three things that look related: NAD+, NMN, and NR. They're all described as "NAD+ support." They're all priced somewhere between expensive and extremely expensive. They're all backed by citations to researchers whose names you half-recognize. And the differences between them are explained, in every product description you've read, in a way that somehow makes it less clear what you should actually be taking, not more.9 min readPeptides for energy and fatigue — what research has explored at the cellular and systemic levelYou don't feel stressed the way you feel hungry. Chronic fatigue doesn't go away when the stressful thing ends. It is there in the morning before anything has happened. It is there after a full night of sleep that didn't restore anything. The coffee works for an hour and then the tiredness reasserts itself, heavier than before. It is not dramatic — fatigue rarely is. It is a narrowing. The things you used to do without thinking about them now require decisions. You lie down in the afternoon not because you want to but because the alternative is worse.10 min readSS-31 and cardiolipin — the mitochondrial membrane storyThe power goes out and the neighborhood goes dark. You don't notice everything that ran on electricity until it stops running. The same logic applies to the mitochondria in your cells — not metaphorically, but mechanically. When the inner architecture of a mitochondrion begins to fail, it isn't one function that drops out. It's everything that electricity powers.8 min readSS-31 in mitochondrial myopathy and heart failure researchThe men who design drugs for heart failure have one of the more humbling jobs in medicine. Heart failure affects tens of millions of people worldwide. The field has produced real breakthroughs — ACE inhibitors, beta-blockers, SGLT2 inhibitors — and yet significant numbers of patients continue to progress toward transplant or death despite optimal medical therapy. When a new mechanism comes along, the desperation to apply it broadly is understandable. The history of cardiology is littered with compounds that worked brilliantly in animal models and failed in human trials. The cautionary lesson keeps being delivered and keeps being partially ignored.9 min read