{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T09:56:51Z","timestamp":1781776611868,"version":"3.54.5"},"reference-count":63,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T00:00:00Z","timestamp":1781308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: The relationship between physical exercise and human longevity constitutes one of the most consequential intersections in contemporary preventive medicine. Although international guidelines recommend 150 min of moderate-intensity exercise weekly, growing evidence suggests that the architecture of optimal exercise is far more complex, encompassing dose, modality, timing across the lifespan, and the paradox risks imposed by extreme endurance. Methods: We included in this narrative review landmark cohort studies, randomized controlled trials, meta-analyses, and expert physiological frameworks published in high-impact cardiovascular, sports medicine, and longevity journals from 1966 to 2024. Results: Cardiorespiratory fitness (CRF), indexed by maximal oxygen uptake (VO2 max), demonstrates the strongest and most linear dose\u2013response relationship with all-cause mortality identified in preventive medicine, with every 1 metabolic equivalent of task (MET) increment associated with a 12\u201315% reduction in mortality risk. The optimal dose of vigorous-intensity exercise follows a J-shaped dose\u2013response curve: 3\u20135 sessions per week generating 1\u20132.4 h of vigorous activity is associated with the lowest all-cause mortality risk in large prospective cohorts, whereas chronic extreme endurance exercise incurs measurable atrial remodeling, patchy myocardial fibrosis, and a 5.3-fold increase in the risk of atrial fibrillation. The importance of exercise types shifts profoundly across the lifespan, transitioning from aerobic capacity effort in the third decade to resistance training in the seventh decade and neuromuscular stability in the eighth. Based on our interpretation of the available evidence, we propose a structured, personalized four-step exercise pathway integrating CRF assessment, lifespan-adapted prescription, lifestyle co-interventions, and periodic reassessment. Conclusions: Among currently available lifestyle interventions, regular exercise is consistently associated with some of the largest and most reproducible reductions in all-cause and cardiovascular mortality observed in prospective cohort data, while remaining accessible and cost-effective.<\/jats:p>","DOI":"10.3390\/jcm15124597","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T08:57:58Z","timestamp":1781513878000},"page":"4597","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Oxygen Imperative: Cardiorespiratory Fitness, Dose-Dependent Exercise Thresholds, and Longevity\u2014A Narrative Review"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7378-7787","authenticated-orcid":false,"given":"Dragos","family":"Cozma","sequence":"first","affiliation":[{"name":"Institute of Cardiovascular Diseases Timisoara, 300310 Timisoara, Romania"},{"name":"Cardiology Department, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania"},{"name":"Research Center of the Institute of Cardiovascular Diseases Timisoara, 300310 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0320-6779","authenticated-orcid":false,"given":"Dan","family":"Gaita","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Diseases Timisoara, 300310 Timisoara, Romania"},{"name":"Cardiology Department, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania"},{"name":"Research Center of the Institute of Cardiovascular Diseases Timisoara, 300310 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8760-5605","authenticated-orcid":false,"given":"Simina","family":"Crisan","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Diseases Timisoara, 300310 Timisoara, Romania"},{"name":"Cardiology Department, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania"},{"name":"Research Center of the Institute of Cardiovascular Diseases Timisoara, 300310 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7351-741X","authenticated-orcid":false,"given":"Cristina","family":"Tudoran","sequence":"additional","affiliation":[{"name":"Department VII, Internal Medicine II, Discipline of Cardiology, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania"},{"name":"County Emergency Hospital \u201cPius Brinzeu\u201d, L. Rebreanu, Nr. 156, 300723 Timisoara, Romania"},{"name":"Center of Molecular Research in Nephrology and Vascular Disease, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea Simina","family":"Dumitrescu","sequence":"additional","affiliation":[{"name":"Department of Physiotherapy, Faculty of Physical Education and Sports, West University of Timi\u0219oara, Bulevardul Vasile P\u00e2rvan 4, 300223 Timisoara, Romania"},{"name":"Neoclinic Medical Center, Calea Doroban\u021bilor 3, 307200 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"V\u0103c\u0103rescu","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Diseases Timisoara, 300310 Timisoara, Romania"},{"name":"Cardiology Department, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania"},{"name":"Research Center of the Institute of Cardiovascular Diseases Timisoara, 300310 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1152\/physrev.00019.2016","article-title":"Role of Inactivity in Chronic Diseases: Evolutionary Insight and Pathophysiological Mechanisms","volume":"97","author":"Booth","year":"2017","journal-title":"Physiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1126\/science.abe5017","article-title":"Daily Energy Expenditure through the Human Life Course","volume":"373","author":"Pontzer","year":"2021","journal-title":"Science"},{"key":"ref_3","unstructured":"World Health Organization (2018). 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