{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:35:32Z","timestamp":1790379332419,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,3,15]],"date-time":"2019-03-15T00:00:00Z","timestamp":1552608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2015R1A5A2008833"],"award-info":[{"award-number":["NRF-2015R1A5A2008833"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The changes in telomere length and mitochondrial DNA copy number (mtDNAcn) are considered to be aging markers. However, many studies have provided contradictory or only fragmentary information about changes of these markers in animal models, due to inaccurate analysis methods and a lack of objective aging standards. To establish chronological aging standards for these two markers, we analyzed telomere length and mtDNAcn in 12 tissues\u2014leukocytes, prefrontal cortex, hippocampus, pituitary gland, adrenal gland, retina, aorta, liver, kidney, spleen, skeletal muscle, and skin\u2014from a commonly used rodent model, C57BL\/6 male mice aged 2\u201324 months. It was found that at least one of the markers changed age-dependently in all tissues. In the leukocytes, hippocampus, retina, and skeletal muscle, both markers changed age-dependently. As a practical application, the aging marker changes were analyzed after chronic immobilization stress (CIS) to see whether CIS accelerated aging or not. The degree of tissue-aging was calculated using each standard curve and found that CIS accelerated aging in a tissue-specific manner. Therefore, it is expected that researchers can use our standard curves to objectively estimate tissue-specific aging accelerating effects of experimental conditions for least 12 tissues in C57BL\/6 male mice.<\/jats:p>","DOI":"10.3390\/cells8030247","type":"journal-article","created":{"date-parts":[[2019,3,18]],"date-time":"2019-03-18T04:06:55Z","timestamp":1552882015000},"page":"247","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Chronological Aging Standard Curves of Telomere Length and Mitochondrial DNA Copy Number in Twelve Tissues of C57BL\/6 Male Mouse"],"prefix":"10.3390","volume":"8","author":[{"given":"Ji Hyeong","family":"Baek","sequence":"first","affiliation":[{"name":"Department of Anatomy and Convergence Medical Sciences, Gyeongsang National University School of Medicine, Jinju 52727, Korea"},{"name":"Institute of Health Sciences, Bio Anti-aging Medical Research Center, Gyeongsang National University, Jinju 52727, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeonwi","family":"Son","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Convergence Medical Sciences, Gyeongsang National University School of Medicine, Jinju 52727, Korea"},{"name":"Institute of Health Sciences, Bio Anti-aging Medical Research Center, Gyeongsang National University, Jinju 52727, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0403-3726","authenticated-orcid":false,"given":"Young-Hoon","family":"Jeong","sequence":"additional","affiliation":[{"name":"Institute of Health Sciences, Bio Anti-aging Medical Research Center, Gyeongsang National University, Jinju 52727, Korea"},{"name":"Department of Internal Medicine, Gyeongsang National University School of Medicine and Cardiovascular Center, Gyeongsang National University Changwon Hospital, Changwon 51472, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6149-5284","authenticated-orcid":false,"given":"Sang Won","family":"Park","sequence":"additional","affiliation":[{"name":"Institute of Health Sciences, Bio Anti-aging Medical Research Center, Gyeongsang National University, Jinju 52727, Korea"},{"name":"Department of Pharmacology and Convergence Medical Sciences, Gyeongsang National University School of Medicine, Jinju 52727, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4159-3888","authenticated-orcid":false,"given":"Hyun Joon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Convergence Medical Sciences, Gyeongsang National University School of Medicine, Jinju 52727, Korea"},{"name":"Institute of Health Sciences, Bio Anti-aging Medical Research Center, Gyeongsang National University, Jinju 52727, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1172\/JCI64125","article-title":"The role of mitochondria in aging","volume":"123","author":"Bratic","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1053\/j.seminhematol.2013.03.030","article-title":"Telomere dynamics in mice and humans","volume":"50","author":"Calado","year":"2013","journal-title":"Semin. Hematol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1038\/labinvest.3700673","article-title":"Role of telomeres and telomerase in genomic instability, senescence and cancer","volume":"87","author":"Deng","year":"2007","journal-title":"Lab. Investig."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"337","DOI":"10.14336\/AD.2013.0400337","article-title":"Mitochondrial DNA damage patterns and aging: Revising the evidences for humans and mice","volume":"4","author":"Kazachkova","year":"2013","journal-title":"Aging Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1111\/joim.12055","article-title":"The role of mitochondrial DNA mutations and free radicals in disease and ageing","volume":"273","author":"Lagouge","year":"2013","journal-title":"J. Intern. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"161","DOI":"10.2174\/1874609808666150122153151","article-title":"Telomere length variations in aging and age-related diseases","volume":"7","author":"Rizvi","year":"2014","journal-title":"Current Aging Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1016\/j.ebiom.2015.07.029","article-title":"Inflammation, but not Telomere Length, Predicts Successful Ageing at Extreme Old Age: A Longitudinal Study of Semi-supercentenarians","volume":"2","author":"Arai","year":"2015","journal-title":"EBioMedicine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1203\/00006450-200209000-00012","article-title":"Telomere Length in the Newborn","volume":"52","author":"Okuda","year":"2002","journal-title":"Pediatr. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1074\/jbc.274.2.962","article-title":"Sequence-specific DNA cleavage by Fe2+-mediated fenton reactions has possible biological implications","volume":"274","author":"Henle","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1006\/excr.1997.3893","article-title":"Preferential accumulation of single-stranded regions in telomeres of human fibroblasts","volume":"239","author":"Petersen","year":"1998","journal-title":"Exp. Cell Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4763","DOI":"10.1021\/bi002721g","article-title":"Site-specific DNA damage at the GGG sequence by UVA involves acceleration of telomere shortening","volume":"40","author":"Oikawa","year":"2001","journal-title":"Biochemistry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/da.20686","article-title":"Depression gets old fast: Do stress and depression accelerate cell aging?","volume":"27","author":"Wolkowitz","year":"2010","journal-title":"Depress. Anxiety"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Bernal, A., and Tusell, L. (2018). Telomeres: Implications for Cancer Development. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010294"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.biocel.2004.09.003","article-title":"Telomere dysfunction in aging and cancer","volume":"37","author":"Gilley","year":"2005","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1097\/PSY.0000000000000545","article-title":"Psychological Stress and Mitochondria: A Systematic Review","volume":"80","author":"Picard","year":"2018","journal-title":"Psychosom. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1073\/pnas.94.2.514","article-title":"Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress","volume":"94","author":"Yakes","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2695","DOI":"10.1093\/hmg\/ddq163","article-title":"High mitochondrial DNA copy number has detrimental effects in mice","volume":"19","author":"Ylikallio","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.bbabio.2010.11.016","article-title":"Regional variation in mitochondrial DNA copy number in mouse brain","volume":"1807","author":"Fuke","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/jcp.1041430122","article-title":"Distinct genomic copy number in mitochondria of different mammalian organs","volume":"143","author":"Veltri","year":"1990","journal-title":"J. Cell. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.mad.2007.10.010","article-title":"Factors impacting human telomere homeostasis and age-related disease","volume":"129","author":"Gilley","year":"2008","journal-title":"Mech. Ageing Dev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"35859","DOI":"10.1038\/srep35859","article-title":"Altered mitochondrial DNA copy number contributes to human cancer risk: Evidence from an updated meta-analysis","volume":"6","author":"Hu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Monroy-Jaramillo, N., Dyukova, E., and Walss-Bass, C. (2017). Telomere length in psychiatric disorders: Is it more than an ageing marker?. World J. Biol. Psychiatry.","DOI":"10.1080\/15622975.2016.1273550"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"77","DOI":"10.14336\/AD.2017.0310","article-title":"Short Telomere Length is Associated with Aging, Central Obesity, Poor Sleep and Hypertension in Lebanese Individuals","volume":"9","author":"Zgheib","year":"2018","journal-title":"Aging Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.neulet.2009.06.025","article-title":"Chronic immobilization stress induces anxiety- and depression-like behaviors and decreases transthyretin in the mouse cortex","volume":"461","author":"Joo","year":"2009","journal-title":"Neurosci. Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.neuropharm.2018.09.040","article-title":"Glutamine has antidepressive effects through increments of glutamate and glutamine levels and glutamatergic activity in the medial prefrontal cortex","volume":"143","author":"Son","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Son, H., Jung, S., Shin, J.H., Kang, M.J., and Kim, H.J. (2018). Anti-Stress and Anti-Depressive Effects of Spinach Extracts on a Chronic Stress-Induced Depression Mouse Model through Lowering Blood Corticosterone and Increasing Brain Glutamate and Glutamine Levels. J. Clin. Med., 7.","DOI":"10.3390\/jcm7110406"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e21","DOI":"10.1093\/nar\/gkn1027","article-title":"Telomere length measurement by a novel monochrome multiplex quantitative PCR method","volume":"37","author":"Cawthon","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1016\/j.cell.2013.11.037","article-title":"Declining NAD+ induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging","volume":"155","author":"Gomes","year":"2013","journal-title":"Cell"},{"key":"ref_29","first-page":"17","article-title":"Real-time PCR assay for measurement of mouse telomeres","volume":"56","author":"Callicott","year":"2006","journal-title":"Comp. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in real-time RT-PCR","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/30.10.e47","article-title":"Telomere measurement by quantitative PCR","volume":"30","author":"Cawthon","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.mrfmmm.2011.04.003","article-title":"Telomere length measurement-caveats and a critical assessment of the available technologies and tools","volume":"730","author":"Aubert","year":"2012","journal-title":"Mutat. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1093\/ije\/dyu191","article-title":"Reproducibility of telomere length assessment: An international collaborative study","volume":"44","author":"Baird","year":"2015","journal-title":"Int. J. Epidemiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1007\/s00391-007-0480-0","article-title":"Telomere shortening and ageing","volume":"40","author":"Jiang","year":"2007","journal-title":"Z. Gerontol. Geriatr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.exger.2009.12.002","article-title":"Does mtDNA nucleoid organization impact aging?","volume":"45","author":"Bogenhagen","year":"2010","journal-title":"Exp. Gerontol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/nrg1606","article-title":"Mitochondrial DNA mutations in human disease","volume":"6","author":"Taylor","year":"2005","journal-title":"Nat. Rev. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"37404","DOI":"10.1038\/srep37404","article-title":"Elevated Mitochondrial DNA Copy Number in Peripheral Blood and Tissue Predict the Opposite Outcome of Cancer: A Meta-Analysis","volume":"6","author":"Chen","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4247","DOI":"10.1182\/blood-2008-05-157974","article-title":"A prospective study of mitochondrial DNA copy number and risk of non-Hodgkin lymphoma","volume":"112","author":"Lan","year":"2008","journal-title":"Blood"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.4103\/0366-6999.216395","article-title":"Reference Intervals of Mitochondrial DNA Copy Number in Peripheral Blood for Chinese Minors and Adults","volume":"130","author":"Xia","year":"2017","journal-title":"Chin. Med. J. (Engl.)"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3176","DOI":"10.1038\/s41598-017-03599-8","article-title":"Aberrant telomere length and mitochondrial DNA copy number in suicide completers","volume":"7","author":"Otsuka","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1016\/j.cub.2015.03.008","article-title":"Molecular Signatures of Major Depression","volume":"25","author":"Cai","year":"2015","journal-title":"Curr. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jpsychires.2016.01.015","article-title":"Shortened telomere length in patients with depression: A meta-analytic study","volume":"76","author":"Lin","year":"2016","journal-title":"J. Psychiatr. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4818","DOI":"10.1073\/pnas.92.11.4818","article-title":"Developmental and tissue-specific regulation of mouse telomerase and telomere length","volume":"92","author":"Prowse","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/3\/247\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:39:07Z","timestamp":1760186347000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/3\/247"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,15]]},"references-count":43,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,3]]}},"alternative-id":["cells8030247"],"URL":"https:\/\/doi.org\/10.3390\/cells8030247","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,15]]}}}