{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T06:05:09Z","timestamp":1780380309044,"version":"3.54.1"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Aging is characterized by progressive loss of physiological complexity, inter-system coordination, and adaptive capacity. While mitochondrial dysfunction, metabolic inflexibility, impaired stress responses, and circadian dysregulation are well established, an integrative systems-level construct linking these processes remains lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To introduce physiological amplitude as a unifying framework describing the bounded dynamic range of coordinated variability across interacting physiological systems.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We develop a conceptual, hypothesis-generating framework grounded in network physiology and systems biology, integrating mitochondrial function, metabolic flexibility, hormetic stress responses, and circadian regulation into a unified architecture of system-level adaptation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Physiological amplitude is defined as the bounded dynamic range within which coordinated multiscale physiological dynamics are maintained. Aging is conceptualized as a progressive contraction of this accessible range across interconnected biological networks. This framework distinguishes physiological amplitude from variability and resilience by positioning it as a higher-order property emerging from constraint-defined interactions across physiological systems.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Physiological amplitude provides an integrative framework for interpreting multiscale physiological dynamics and generates testable hypotheses for quantification using continuous monitoring and network-based analysis. As a candidate systems-level descriptor, it may support the development of integrative biomarkers of aging and metabolic decline, pending empirical validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fragi.2026.1837722","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T05:41:19Z","timestamp":1780378879000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Physiological amplitude: a systems-level framework for adaptive capacity in aging and metabolism"],"prefix":"10.3389","volume":"7","author":[{"given":"Grazyna","family":"Sepczynska","sequence":"first","affiliation":[{"name":"Independent Researcher","place":["Toronto, ON, Canada"]},{"name":"Eye Institute","place":["Czestochowa, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/nphys3178","article-title":"Network physiology: how organ systems dynamically interact","volume":"11","author":"Bartsch","year":"2015","journal-title":"Nat. Phys."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1126\/science.1195027","article-title":"Circadian integration of metabolism and energetics","volume":"330","author":"Bass","year":"2010","journal-title":"Science"},{"key":"B3","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/s12079-010-0119-1","article-title":"Hormesis provides a generalized quantitative estimate of biological plasticity","volume":"5","author":"Calabrese","year":"2011","journal-title":"J. Cell Commun. Signal."},{"key":"B4","doi-asserted-by":"publisher","first-page":"M146","DOI":"10.1093\/gerona\/56.3.M146","article-title":"Frailty in older adults: evidence for a phenotype","volume":"56","author":"Fried","year":"2001","journal-title":"J. Gerontology Ser. A"},{"key":"B5","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/S0197-4580(01)00266-4","article-title":"What is physiologic complexity and how does it change with aging and disease?","volume":"23","author":"Goldberger","year":"","journal-title":"Neurobiol. Aging"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2466","DOI":"10.1073\/pnas.012579499","article-title":"Fractal dynamics in physiology: alterations with disease and aging","volume":"99","author":"Goldberger","year":"","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1016\/j.cmet.2017.04.015","article-title":"Metabolic flexibility in health and disease","volume":"25","author":"Goodpaster","year":"2017","journal-title":"Cell Metab."},{"key":"B8","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1016\/j.cell.2014.10.029","article-title":"Integrative biology of exercise","volume":"159","author":"Hawley","year":"2014","journal-title":"Cell"},{"key":"B9","doi-asserted-by":"publisher","first-page":"100201","DOI":"10.1088\/1367-2630\/18\/10\/100201","article-title":"Focus on the emerging new fields of network physiology and network medicine","volume":"18","author":"Ivanov","year":"2016","journal-title":"New J. Phys."},{"key":"B10","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1016\/j.cell.2014.10.039","article-title":"Geroscience: linking aging to chronic disease","volume":"159","author":"Kennedy","year":"2014","journal-title":"Cell"},{"key":"B11","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1038\/nrg1471","article-title":"Biological robustness","volume":"5","author":"Kitano","year":"2004","journal-title":"Nat. Rev. Genet."},{"key":"B12","doi-asserted-by":"publisher","first-page":"B115","DOI":"10.1093\/gerona\/57.3.B115","article-title":"Dynamics of stability: the physiologic basis of functional health and frailty","volume":"57","author":"Lipsitz","year":"2002","journal-title":"J. Gerontology Ser. A"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"L\u00f3pez-Ot\u00edn","year":"2013","journal-title":"Cell"},{"key":"B14","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1100\/tsw.2001.58","article-title":"Accumulation of deficits as a proxy measure of aging","volume":"1","author":"Mitnitski","year":"2001","journal-title":"ScientificWorldJournal"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1016\/j.cell.2014.11.034","article-title":"Metabolic inflexibility: when mitochondrial indecision leads to metabolic gridlock","volume":"159","author":"Muoio","year":"2014","journal-title":"Cell"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1016\/j.cell.2012.02.035","article-title":"Mitochondria: in sickness and in health","volume":"148","author":"Nunnari","year":"2012","journal-title":"Cell"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1243417","DOI":"10.1126\/science.1243417","article-title":"Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism","volume":"342","author":"Peek","year":"2013","journal-title":"Science"},{"key":"B18","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1038\/nrm.2016.34","article-title":"The rise of mitochondria in medicine","volume":"17","author":"Picard","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.arr.2007.03.002","article-title":"Hormesis in aging","volume":"7","author":"Rattan","year":"2008","journal-title":"Ageing Res. Rev."},{"key":"B20","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1152\/physrev.1997.77.3.731","article-title":"Cellular energy utilization and molecular origin of metabolic rate","volume":"77","author":"Rolfe","year":"1997","journal-title":"Physiol. Rev."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.3390\/ijms27031345","article-title":"Energy allocation resilience and endocrine integration","volume":"27","author":"Schuler","year":"2026","journal-title":"Int. J. Mol. Sci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1016\/j.molcel.2016.01.028","article-title":"The mitochondrial basis of aging","volume":"61","author":"Sun","year":"2016","journal-title":"Mol. Cell"},{"key":"B23","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1038\/nrc3365","article-title":"Mitochondria and cancer","volume":"12","author":"Wallace","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"B24","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1093\/gerona\/glv202","article-title":"Physical resilience in older adults: systematic review","volume":"71","author":"Whitson","year":"2016","journal-title":"J. Gerontology Ser. A"}],"container-title":["Frontiers in Aging"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fragi.2026.1837722\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T05:41:20Z","timestamp":1780378880000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fragi.2026.1837722\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,2]]},"references-count":24,"alternative-id":["10.3389\/fragi.2026.1837722"],"URL":"https:\/\/doi.org\/10.3389\/fragi.2026.1837722","relation":{},"ISSN":["2673-6217"],"issn-type":[{"value":"2673-6217","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,2]]},"article-number":"1837722"}}