{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T03:35:19Z","timestamp":1790566519740,"version":"4.1.0"},"reference-count":56,"publisher":"Walter de Gruyter GmbH","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,25]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In the area of the Medical Sciences, the chronological age has always been, and still is, an indicator by which we try to understand the health status of an individual. However, besides considering people born with an already expressed disease, each human genome has sequence alterations called predisposing mutations; carriers of such genetic alterations have an increased risk of contracting diseases during their life. In addition, the exposome, i.e. the totality of environmental<jats:italic>noxae<\/jats:italic>(\u201chits\u201d) to which our body is exposed throughout life (through ingestion, breathing, body surface hits, and psychosociological stress agents, etc.) contributes to increase gradually but inexorably the frailty of an organism, and this process is usually referred to as \u201cphysiological ageing\u201d. This position paper proposes that we invert our visual angle and view the passage-of-time not as the cause of diseases, but consider the genome alterations present at birth and the<jats:italic>noxae<\/jats:italic>received during our life as the real major causes of ageing. The Biomedical Sciences are now increasingly unraveling the etiopathogenesis of most chronic degenerative diseases; thus, it will be possible to monitor and treat those that most contribute to the increased frailty of each person, which is now referred to with the misnomer \u201cphysiological ageing\u201d. These concepts are not banal; indeed, they imply that we must try to avoid the causes of alterations that result later in chronic degenerative diseases. Thus, we should shift our attention from the cure to the prevention of alterations\/diseases also to improve both the length and quality of our life. Moreover, this approach involves real personalized or individualized medicine, thus conferring a more direct benefit to each of us by finalizing either the cure or the monitoring of diseases.<\/jats:p>","DOI":"10.1515\/cclm-2020-0125","type":"journal-article","created":{"date-parts":[[2020,4,17]],"date-time":"2020-04-17T13:13:28Z","timestamp":1587129208000},"page":"1635-1644","source":"Crossref","is-referenced-by-count":27,"title":["The shift of the paradigm between ageing and diseases"],"prefix":"10.1515","volume":"58","author":[{"given":"Francesco","family":"Salvatore","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnologies , University of Naples Federico II , Naples , Italy"},{"name":"CEINGE Biotecnologie Avanzate Scarl , Naples , Italy"},{"name":"Inter-University Center for Multifactorial and Multigenes Chronic Human Diseases, Federico II Naples, Tor Vergata Roma2, Chieti-Pescara Universities , Naples , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2020,4,13]]},"reference":[{"key":"2023033111254779833_j_cclm-2020-0125_ref_001","doi-asserted-by":"crossref","unstructured":"Shrestha A, Martin C, Burton M, Walters S, Collins K, Wyld L. Quality of life versus length of life considerations in cancer patients: a systematic literature review. Psychooncology 2019;28:1367\u201380.","DOI":"10.1002\/pon.5054"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_002","doi-asserted-by":"crossref","unstructured":"The Lancet Respiratory Medicine. Prolonging life at all costs: quantity versus quality. Lancet Respir Med 2016;4:165.","DOI":"10.1016\/S2213-2600(16)00059-X"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_003","doi-asserted-by":"crossref","unstructured":"Hawsawi YM, Al-Numair NS, Sobahy TM, Al-Ajmi AM, Al-Harbi RM, Baghdadi MA, et al. The role of BRCA1\/2 in hereditary and familial breast and ovarian cancers. Mol Genet Genomic Med 2019;7:1\u20137.","DOI":"10.1002\/mgg3.879"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_004","doi-asserted-by":"crossref","unstructured":"Wild CP. The exposome: from concept to utility. Int J Epidemiol 2012;41:24\u201332.","DOI":"10.1093\/ije\/dyr236"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_005","doi-asserted-by":"crossref","unstructured":"Agier L, Basaga\u00f1a X, Maitre L, Granum B, Bird PK, Casas M, et al. Early-life exposome and lung function in children in Europe: an analysis of data from the longitudinal, population-based HELIX cohort. Lancet Planet Heal 2019;3:e81\u201392.","DOI":"10.1016\/S2542-5196(19)30010-5"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_006","doi-asserted-by":"crossref","unstructured":"Tamayo-Uria I, Maitre L, Thomsen C, Nieuwenhuijsen MJ, Chatzi L, Siroux V, et al. The early-life exposome: description and patterns in six European countries. Environ Int 2019;123:189\u2013200.","DOI":"10.1016\/j.envint.2018.11.067"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_007","doi-asserted-by":"crossref","unstructured":"Strafella C, Caputo V, Galota MR, Zampatti S, Marella G, Mauriello S, et al. Application of precision medicine in neurodegenerative diseases. Front Neurol 2018;9:701.","DOI":"10.3389\/fneur.2018.00701"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_008","doi-asserted-by":"crossref","unstructured":"Abdel-Daim MM, Zakhary NI, Aleya L, Bung\u01ceu SG, Bohara RA, Siddiqi NJ. Aging, metabolic, and degenerative disorders: biomedical value of antioxidants. Oxid Med Cell Longev 2018;2018:2098123.","DOI":"10.1155\/2018\/2098123"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_009","unstructured":"Olshansky SJ, Martin GM, Kirkland JL, editors. Aging: the longevity divided, 1st ed. Woodbury, NY, USA: Cold Spring Harbor Laboratory Press, 2015:243."},{"key":"2023033111254779833_j_cclm-2020-0125_ref_010","doi-asserted-by":"crossref","unstructured":"Olshansky SJ. Articulating the case for the longevity dividend. Cold Spring Harb Perspect Med 2016;6:a025940.","DOI":"10.1101\/cshperspect.a025940"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_011","doi-asserted-by":"crossref","unstructured":"Sierra F. The emergence of geroscience as an interdisciplinary approach to the enhancement of health span and life span. Cold Spring Harb Perspect Med 2016;6:a025163.","DOI":"10.1101\/cshperspect.a025163"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_012","doi-asserted-by":"crossref","unstructured":"Han JDJ, Xia X, Chen W, McDermott J. Molecular and phenotypic biomarkers of aging. F1000Research 2017;6:860.","DOI":"10.12688\/f1000research.10692.1"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_013","doi-asserted-by":"crossref","unstructured":"Dodig S, \u010cepelak I, Pavi\u0107 I. Hallmarks of senescence and aging. Biochem Medica 2019;29:030501.","DOI":"10.11613\/BM.2019.030501"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_014","doi-asserted-by":"crossref","unstructured":"Wagner KH, Cameron-Smith D, Wessner B, Franzke B. Biomarkers of aging: from function to molecular biology. Nutrients 2016;8:338.","DOI":"10.3390\/nu8060338"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_015","doi-asserted-by":"crossref","unstructured":"Jia L, Zhang W, Chen X. Common methods of biological age estimation. Clin Interv Aging 2017;12:759\u201372.","DOI":"10.2147\/CIA.S134921"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_016","doi-asserted-by":"crossref","unstructured":"Jylh\u00e4v\u00e4 J, Pedersen NL, H\u00e4gg S. Biological age predictors. EBioMedicine 2017;21:29\u201336.","DOI":"10.1016\/j.ebiom.2017.03.046"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_017","unstructured":"Salvatore F. Dall\u2019invecchiamento alla longevit\u00e0 in buona salute: da un ossimoro ad un\u2019endiade. Il contributo della medicina di laboratorio alla medicina personalizzata. In: Ciaccio M, Lippi G, editors. Biochimica Clinica e Medicina di Laboratorio. Napoli, Italy: Edises, 2019:759\u201366."},{"key":"2023033111254779833_j_cclm-2020-0125_ref_018","unstructured":"Salvatore F. Healthy aging: an oxymoron or a hendiadys \u2013 Rendiconti della accademia nazionale delle scienze, detta dei XL \u2013 Memorie di Scienze Fisiche e Naturali. Serie V, vol. XXXIV, parte II, 2010:31\u201345."},{"key":"2023033111254779833_j_cclm-2020-0125_ref_019","unstructured":"Carmona JJ, Michan S. Biology of healthy aging and longevity. Rev Invest Clin 2016;68:7\u201316."},{"key":"2023033111254779833_j_cclm-2020-0125_ref_020","doi-asserted-by":"crossref","unstructured":"Dzau VJ, Inouye SK, Rowe JW, Finkelman E, Yamada T. Enabling healthful aging for all \u2013 the National academy of medicine grand challenge in healthy longevity. N Engl J Med 2019;381:1699\u2013701.","DOI":"10.1056\/NEJMp1912298"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_021","doi-asserted-by":"crossref","unstructured":"Navaratnarajah A, Jackson SH. The physiology of ageing. Med (United Kingdom) 2017;45:6\u201310.","DOI":"10.1016\/j.mpmed.2016.10.008"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_022","doi-asserted-by":"crossref","unstructured":"Radder JE, Shapiro SD, Berndt A. Personalized medicine for chronic, complex diseases: chronic obstructive pulmonary disease as an example. Per Med 2014;11:669\u201379.","DOI":"10.2217\/pme.14.51"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_023","doi-asserted-by":"crossref","unstructured":"Bell CG, Lowe R, Adams PD, Baccarelli AA, Beck S, Bell JT, et al. DNA methylation aging clocks: challenges and recommendations. Genome Biol 2019;20:249.","DOI":"10.1186\/s13059-019-1824-y"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_024","doi-asserted-by":"crossref","unstructured":"Levine M, Lu A, Quach A, Chen B, Assimes T, Bandinelli S, et al. An epigenetic biomarker of aging for lifespan and healthspan. Ageing 2018;10:573\u201391.","DOI":"10.18632\/aging.101414"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_025","unstructured":"Heidegger M. Essere e tempo, 3rd ed. Milan, Italy: Longanesi, 2005:589."},{"key":"2023033111254779833_j_cclm-2020-0125_ref_026","unstructured":"Rovelli C. L\u2019ordine del tempo, Piccola Biblioteca Adelphi. In: Riquier C, editor. Bergson H. Historie de l\u2019id\u00e9e de temple, 11th ed. PUF, Paris: Course au College de France, 2016, Vol. 2017:705."},{"key":"2023033111254779833_j_cclm-2020-0125_ref_027","doi-asserted-by":"crossref","unstructured":"Borysiewicz LK. Prevention is better than cure. Lancet 2010;9:572\u201383.","DOI":"10.7861\/clinmedicine.9-6-572"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_028","doi-asserted-by":"crossref","unstructured":"Loeser RF, Collins JA, Diekman BO. Ageing and the pathogenesis of osteoarthritis. Nat Rev Rheumatol 2016;12:412\u201320.","DOI":"10.1038\/nrrheum.2016.65"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_029","doi-asserted-by":"crossref","unstructured":"Y\u00e1\u00f1ez A, Cho SH, Soriano JB, Rosenwasser LJ, Rodrigo GJ, Rabe KF, et al. Asthma in the elderly: what we know and what we have yet to know. World Allergy Organ J 2014;7:8.","DOI":"10.1186\/1939-4551-7-8"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_030","doi-asserted-by":"crossref","unstructured":"Estape T. Cancer in the elderly: challenges and barriers. Asia-Pacific J Oncol Nurs 2018;5:40\u20132.","DOI":"10.4103\/apjon.apjon_52_17"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_031","doi-asserted-by":"crossref","unstructured":"Paneni F, Diaz Ca\u00f1estro C, Libby P, L\u00fcscher TF, Camici GG. The aging cardiovascular system: understanding it at the cellular and clinical levels. J Am Coll Cardiol 2017;69:1952\u201367.","DOI":"10.1016\/j.jacc.2017.01.064"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_032","doi-asserted-by":"crossref","unstructured":"Mallappallil M, Friedman EA, Delano BG, Mcfarlane SI, Salifu MO. Chronic kidney disease in the elderly: evaluation and management. Clin Pract 2014;11:525\u201335.","DOI":"10.2217\/cpr.14.46"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_033","doi-asserted-by":"crossref","unstructured":"Incalzi RA, Scarlata S, Pennazza G, Santonico M, Pedone C. Chronic obstructive pulmonary disease in the elderly. Eur J Intern Med 2014;25:320\u20138.","DOI":"10.1016\/j.ejim.2013.10.001"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_034","doi-asserted-by":"crossref","unstructured":"Xia X, Jiang Q, McDermott J, Han JDJ. Aging and Alzheimer\u2019s disease: comparison and associations from molecular to system level. Aging Cell 2018;17:e12802.","DOI":"10.1111\/acel.12802"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_035","doi-asserted-by":"crossref","unstructured":"Kalyani RR, Golden SH, Cefalu WT. Diabetes and aging: unique considerations and goals of care. Diabetes Care 2017;40:440\u20133.","DOI":"10.2337\/dci17-0005"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_036","doi-asserted-by":"crossref","unstructured":"Coco D Lo, Lopez G, Corrao S. Cognitive impairment and stroke in elderly patients. Vasc Health Risk Manag 2016;12:105\u201316.","DOI":"10.2147\/VHRM.S75306"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_037","doi-asserted-by":"crossref","unstructured":"Wang S, Ren J. Obesity paradox in aging: from prevalence to pathophysiology. Prog Cardiovasc Dis 2018;61:182\u20139.","DOI":"10.1016\/j.pcad.2018.07.011"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_038","doi-asserted-by":"crossref","unstructured":"Curtis JR, Safford MM. Management of osteoporosis among the elderly with other chronic medical conditions. Drugs Aging 2012;29:549\u201364.","DOI":"10.2165\/11599620-000000000-00000"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_039","doi-asserted-by":"crossref","unstructured":"Patel R, McKinnon BJ. Hearing loss in the elderly. Clin Geriatr Med 2018;34:163\u201374.","DOI":"10.1016\/j.cger.2018.01.001"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_040","doi-asserted-by":"crossref","unstructured":"Lochlainn MN, Kenny RA. Sexual activity and aging. J Am Med Dir Assoc 2013;14:565\u201372.","DOI":"10.1016\/j.jamda.2013.01.022"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_041","doi-asserted-by":"crossref","unstructured":"Ottaviano G, Frasson G, Nardello E, Martini A. Olfaction deterioration in cognitive disorders in the elderly. Aging Clin Exp Res 2016;28:37\u201345.","DOI":"10.1007\/s40520-015-0380-x"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_042","unstructured":"Pelletier AL, Rojas-Roldan L, Coffin J. Vision loss in older adults. Am Fam Physician 2016;94:219\u201326. Review. Erratum in: Am Fam Physician 2016;94:344."},{"key":"2023033111254779833_j_cclm-2020-0125_ref_043","doi-asserted-by":"crossref","unstructured":"Imoscopi A, Inelmen EM, Sergi G, Miotto F, Manzato E. Taste loss in the elderly: epidemiology, causes and consequences. Aging Clin Exp Res 2012;24:570\u20139.","DOI":"10.1007\/BF03654833"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_044","doi-asserted-by":"crossref","unstructured":"Sanford AM. Anorexia of aging and its role for frailty. Curr Opin Clin Nutr Metab Care 2017;20:54\u201360.","DOI":"10.1097\/MCO.0000000000000336"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_045","doi-asserted-by":"crossref","unstructured":"Dhillon RJ, Hasni S. Pathogenesis and management of sarcopenia. Clin Geriatr Med 2017;33:17\u201326.","DOI":"10.1016\/j.cger.2016.08.002"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_046","doi-asserted-by":"crossref","unstructured":"Zhang S, Duan E. Fighting against skin aging: the way from bench to bedside. Cell Transplant 2018;27:729\u201338.","DOI":"10.1177\/0963689717725755"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_047","doi-asserted-by":"crossref","unstructured":"Sanada F, Taniyama Y, Muratsu J, Otsu R, Shimizu H, Rakugi H, et al. Source of chronic inflammation in aging. Front Cardiovasc Med 2018;5:12.","DOI":"10.3389\/fcvm.2018.00012"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_048","doi-asserted-by":"crossref","unstructured":"Chung HY, Kim DH, Lee EK, Chung KW, Chung S, Lee B, et al. Redefining chronic inflammation in aging and age-related diseases: proposal of the senoinflammation concept. Aging Dis 2019;10:367\u201382.","DOI":"10.14336\/AD.2018.0324"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_049","doi-asserted-by":"crossref","unstructured":"Tomasetti C, Vogelstein B. Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science 2015;347:78\u201381.","DOI":"10.1126\/science.1260825"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_050","doi-asserted-by":"crossref","unstructured":"Luzzatto L, Pandolfi PP. Causality and chance in the development of cancer. N Engl J Med 2015;373:84\u20138.","DOI":"10.1056\/NEJMsb1502456"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_051","doi-asserted-by":"crossref","unstructured":"Dellino GI, Palluzzi F, Chiariello AM, Piccioni R, Bianco S, Furia L, et al. Release of paused RNA polymerase II at specific loci favors DNA double-strand-break formation and promotes cancer translocations. Nat Genet 2019;51:1011\u201323.","DOI":"10.1038\/s41588-019-0421-z"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_052","doi-asserted-by":"crossref","unstructured":"Corr\u00e0 U, Piepoli MF. Secondary prevention: where we are. Eur J Prev Cardiol 2017;24:14\u201321.","DOI":"10.1177\/2047487317704978"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_053","doi-asserted-by":"crossref","unstructured":"Aminde LN, Takah NF, Zapata-Diomedi B, Veerman JL. Primary and secondary prevention interventions for cardiovascular disease in low-income and middle-income countries: a systematic review of economic evaluations. Cost Eff Resour Alloc 2018;16:22.","DOI":"10.1186\/s12962-018-0108-9"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_054","doi-asserted-by":"crossref","unstructured":"Oeppen J, Vaupel JW. Broken limits to life expectancy. Science 2002;296:1029\u201331.","DOI":"10.1126\/science.1069675"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_055","doi-asserted-by":"crossref","unstructured":"Barbi E, Lagona F, Marsili M, Vaupel JW, Wachter KW. The plateau of human mortality: demography of longevity pioneers. Science 2018;360:1459\u201361.","DOI":"10.1126\/science.aat3119"},{"key":"2023033111254779833_j_cclm-2020-0125_ref_056","doi-asserted-by":"crossref","unstructured":"Dolgin E. There\u2019s no limit to longevity, says study that revives human lifespan debate. Nature 2018;559:14\u20135.","DOI":"10.1038\/d41586-018-05582-3"}],"container-title":["Clinical Chemistry and Laboratory Medicine (CCLM)"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyter.com\/view\/journals\/cclm\/58\/10\/article-p1635.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/cclm-2020-0125\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/cclm-2020-0125\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,4]],"date-time":"2024-08-04T06:22:11Z","timestamp":1722752531000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/cclm-2020-0125\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,13]]},"references-count":56,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,2,7]]},"published-print":{"date-parts":[[2020,9,25]]}},"alternative-id":["10.1515\/cclm-2020-0125"],"URL":"https:\/\/doi.org\/10.1515\/cclm-2020-0125","relation":{},"ISSN":["1437-4331","1434-6621"],"issn-type":[{"value":"1437-4331","type":"electronic"},{"value":"1434-6621","type":"print"}],"subject":[],"published":{"date-parts":[[2020,4,13]]}}}