> ## Content Index > Fetch the complete content index at: https://insights.cortexbio.co.uk/llms.txt > Use this file to discover other available public pages before exploring further. # Tiredness Is Not One Thing. It Is Five. - URL: https://insights.cortexbio.co.uk/tiredness-is-not-one-thing/ - Published: 2026-06-22T16:42:12.000Z - Description: Older adults are told they are simply tired. But ageing fatigue is at least five different biologies wearing one clinical label — and that matters for what works. - Author: Dima Martini-Drew MD - Tags: CortexBio In Brief, Ageing, Public [ ![CortexBio® logo](https://storage.ghost.io/c/44/61/44611ba7-2b2b-4b35-8317-4721c2e47a53/content/images/2026/06/cortexbio-logo-r.png) ](https://cortexbio.co.uk/?ref=insights.cortexbio.co.uk) CORTEXBIO IN BRIEF · FREE By [Dima Martini-Drew, MD — Founder, CortexBio®](https://cortexbio.co.uk/?ref=insights.cortexbio.co.uk)· 5 min read· IN BRIEF --- ⚠️ **Educational only.** This article presents published evidence and the author's interpretation of it. It is not medical advice and does not establish a clinician-reader relationship. Speak with your clinician before changing any treatment, supplement, or rehabilitation programme. Where drug categories are mentioned, no off-label use is endorsed. 1-minute summary - Around a third of people over 60 report fatigue, but "fatigue" hides at least five different biologies. - Because we measure it as one thing, treatment trials keep producing muddy, average results. - You can start noticing which kind of tiredness you have this week — no purchase required. In this Brief 1. [The word that hides five problems](#section-1) · 2 min 2. [Why one label stalls the science](#section-2) · 2 min 3. [What to do with this, this week](#section-action) · 1 min ## The word that hides five problems · 2 min When an older person says "I'm exhausted," the word does an enormous amount of work — and most of it is invisible. Between 15% and 45% of adults over 65 report fatigue, with a pooled estimate of roughly 31% in the over-60s.[1](#ref-1) That single word is asked to cover a cell that has run out of energy currency, a body simmering with low-grade inflammation, a brain whose immune cells are misfiring, a chemical imbalance starving the brain of serotonin, and a metabolism that can no longer handle its own fuel. These are not shades of the same thing. They are five different machines breaking in five different ways, and at [CortexBio®](https://cortexbio.co.uk/?ref=insights.cortexbio.co.uk) we think the habit of calling them all "fatigue" is one of the quietest failures in the medicine of ageing. There is a detail here that surprises most people. General, everyday tiredness does not simply climb with age — in several large studies, older adults report *less* of it than the middle-aged, as expectations recalibrate.[2](#ref-2) What rises steeply is something different: *restricting* fatigue, the kind severe enough to curtail what you do for months at a time. In women aged 80–89, one long-running family study found it present in 74.8%.[3](#ref-3) ![Line chart showing general fatigue plateauing across age bands while restricting fatigue rises steeply to over 90 percent](https://storage.ghost.io/c/44/61/44611ba7-2b2b-4b35-8317-4721c2e47a53/content/images/2026/06/epidemiology.jpg) Figure 2\. General fatigue plateaus with age, but restricting fatigue climbs steeply — reaching 74.8% in women aged 80–89\. Get In Brief in your inbox — free, every fortnight. One short article every fortnight on metabolism, ageing, and the gaps in how medicine names them. [Subscribe free →](https://insights.cortexbio.co.uk/#/portal/signup?utm%5Fsource=in-brief&utm%5Fmedium=newsletter&utm%5Fcampaign=fatigue-ageing-trilogy&utm%5Fcontent=in-brief-mid-article-hook) ## Why one label stalls the science · 2 min Here is the practical cost of the single word. Imagine four people who all score the same on a standard fatigue questionnaire. One has a cellular energy failure; one is inflamed; one has a brain-immune problem; one crashes after every meal because of insulin resistance. The questionnaire cannot tell them apart — yet they are unlikely to respond to the same treatment.[4](#ref-4) So when a trial enrols all four and tests one intervention, the result is a diluted average — and often "no effect," even when the treatment works beautifully for one of the four. This is exactly the trap that cancer medicine climbed out of: tumours with the same name turned out to have different drivers, and progress only came once they were named and matched to the right therapy.[5](#ref-5) The fix is not a better questionnaire. It is *names that carry biology* — so the right treatment can finally be tested in the right person. We have proposed five: a cellular-energy type, an inflammatory type, a brain-immune type, a serotonin-pathway type, and a fuel-handling type.[6](#ref-6) ![Diagram of a central FATIGUE circle with five coloured arrows pointing to five different molecular icons](https://storage.ghost.io/c/44/61/44611ba7-2b2b-4b35-8317-4721c2e47a53/content/images/2026/06/problem.jpg) Figure 3\. One clinical label, five distinct failure modes — each with its own driver, its own marker, and its own candidate intervention. Which of the five is yours? That is the question this short article deliberately leaves open — because the honest answer needs a clinical assessment, not a guess. What you *can* do is start gathering the clues. ## What to do with this, this week · 1 min For one week, keep a simple note of *when* your tiredness is worst and *what shape* it takes. Is it a physical heaviness after exertion? A foggy lack of motivation? A slump that follows meals? The pattern — not the score — is the first real clue to which biology is driving it, and it costs nothing to start noticing today. The clinical assessment framework — how to read those patterns into the five subtype signatures and match each to a marker and a measure — sits in [CortexBio In Practice](https://insights.cortexbio.co.uk/ageing-fatigue-subtypes/?utm%5Fsource=in-brief&utm%5Fmedium=newsletter&utm%5Fcampaign=fatigue-ageing-trilogy&utm%5Fcontent=in-brief-to-in-practice-teaser). £19/month, cancel any time. The strategic and market-level implications — including why the therapeutic pipeline has stalled and how rare inherited diseases unlock the biology — sit in [CortexBio In Consult](https://insights.cortexbio.co.uk/ageing-fatigue-subtypes-consult/?utm%5Fsource=in-brief&utm%5Fmedium=newsletter&utm%5Fcampaign=fatigue-ageing-trilogy&utm%5Fcontent=in-brief-to-in-consult-teaser). £49/month for the strategic tier. This article centres British data, but the mechanism is global. In the United States, the CDC reports that fatigue is among the most common reasons older adults give for limiting their daily activity, with comparable patterns across the ageing population.[7](#ref-7) Readers in Canada, Australia, and the European Union face the same biology with different system overlays. About the author Dima Martini-Drew, MD is the founder of [CortexBio®](https://cortexbio.co.uk/?ref=insights.cortexbio.co.uk), a metabolic-innovation company working on rare disease and ageing. Thirty years inside drug development and regulatory systems across eleven countries. Writes from Cobham, Surrey, the United Kingdom. THE CORTEXBIO® INSIGHTS TRILOGY IN BRIEF Free Monthly digest. One headline, one action, one open gap. [Subscribe free →](https://insights.cortexbio.co.uk/#/portal/signup?utm%5Fsource=in-brief&utm%5Fmedium=newsletter&utm%5Fcampaign=fatigue-ageing-trilogy&utm%5Fcontent=in-brief-to-in-brief-subscribe) IN PRACTICE £19 / month Clinical-tier framework. The five signatures, markers, and matched interventions. [Upgrade to In Practice →](https://insights.cortexbio.co.uk/ageing-fatigue-subtypes/?utm%5Fsource=in-brief&utm%5Fmedium=newsletter&utm%5Fcampaign=fatigue-ageing-trilogy&utm%5Fcontent=in-brief-to-in-practice-upgrade) IN CONSULT £49 / month Strategic tier. Pipeline economics, the rare-disease bridge, dated forecasts. [Upgrade to In Consult →](https://insights.cortexbio.co.uk/ageing-fatigue-subtypes-consult/?utm%5Fsource=in-brief&utm%5Fmedium=newsletter&utm%5Fcampaign=fatigue-ageing-trilogy&utm%5Fcontent=in-brief-to-in-consult-upgrade) Abbreviations used in this article CDC Centers for Disease Control and Prevention (United States) ## References 1. Yoon S, et al. Global prevalence of fatigue in the general population: a systematic review and meta-analysis. *BMC Public Health* 2024\. Pooled fatigue prevalence approximately 31% in adults over 60\. [doi.org/10.1186/s12889-024-17753-1](https://doi.org/10.1186/s12889-024-17753-1?ref=insights.cortexbio.co.uk). [↩](#cite-1) 2. Moreh E, Jacobs JM, Stessman J. Fatigue, function, and mortality in older adults. *J Gerontol A Biol Sci Med Sci* 2010;65(8):887–895\. [doi.org/10.1093/gerona/glq064](https://doi.org/10.1093/gerona/glq064?ref=insights.cortexbio.co.uk). [↩](#cite-2) 3. Simonsick EM, Glynn NW, Jerome GJ, et al. Fatigability in high-functioning adults: who is most susceptible? *J Am Geriatr Soc* 2016;64(4):736–742\. [doi.org/10.1111/jgs.14027](https://doi.org/10.1111/jgs.14027?ref=insights.cortexbio.co.uk). [↩](#cite-3) 4. Bower JE. Cancer-related fatigue: mechanisms, risk factors, and treatments. *Nat Rev Clin Oncol* 2014;11(10):597–609\. [doi.org/10.1038/nrclinonc.2014.127](https://doi.org/10.1038/nrclinonc.2014.127?ref=insights.cortexbio.co.uk). [↩](#cite-4) 5. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: an expanding universe. *Cell* 2023;186(2):243–278\. [doi.org/10.1016/j.cell.2022.11.001](https://doi.org/10.1016/j.cell.2022.11.001?ref=insights.cortexbio.co.uk). [↩](#cite-5) 6. Martini-Drew D. Ageing fatigue subtypes: a mechanism-based nomenclature and translational research framework. *CortexBio White Paper* 2026;CB-FATIGUE-AGEING-01\. [cortexbio.co.uk](https://cortexbio.co.uk/?ref=insights.cortexbio.co.uk). [↩](#cite-6) 7. Centers for Disease Control and Prevention. FastStats — older persons' health and limitations in daily activity. Atlanta: CDC; 2024\. Available from: [cdc.gov/nchs/fastats/older-american-health.htm](https://www.cdc.gov/nchs/fastats/older-american-health.htm?ref=insights.cortexbio.co.uk). [↩](#cite-7)