{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:02:33Z","timestamp":1792440153321,"version":"4.5.0"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Obes"],"published-print":{"date-parts":[[2026,4]]},"DOI":"10.1038\/s41366-025-02007-w","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T18:34:49Z","timestamp":1767638089000},"page":"797-805","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The effect of obesity and aging on NAD+\/Sirtuin metabolism transcription and DNA methylation in subcutaneous adipose tissue of monozygotic twin pairs discordant for BMI"],"prefix":"10.1038","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6655-4415","authenticated-orcid":false,"given":"Helena A. K.","family":"Lapatto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8608-541X","authenticated-orcid":false,"given":"Birgitta W.","family":"van der Kolk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7624-7948","authenticated-orcid":false,"given":"Maheswary","family":"Muniandy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6342-0577","authenticated-orcid":false,"given":"Sini","family":"Heinonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5770-6475","authenticated-orcid":false,"given":"Aino","family":"Heikkinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Alvarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0943-6076","authenticated-orcid":false,"given":"Seung Hyuk T.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riikka","family":"Jokinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper","family":"Lundbom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juho","family":"Kuula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antti","family":"Hakkarainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per-Henrik","family":"Groop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3716-2455","authenticated-orcid":false,"given":"Jaakko","family":"Kaprio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taru","family":"Tukiainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3661-7400","authenticated-orcid":false,"given":"Miina","family":"Ollikainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e4ivi","family":"Pajukanta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eija","family":"Pirinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8522-1288","authenticated-orcid":false,"given":"Kirsi H.","family":"Pietil\u00e4inen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"key":"2007_CR1","unstructured":"Obesity and overweight. https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/obesity-and-overweight."},{"key":"2007_CR2","unstructured":"World Health Organization. Progress report on the United Nations Decade of Healthy Ageing, 2021-2023. 2023. https:\/\/www.who.int\/publications\/i\/item\/9789240079694."},{"key":"2007_CR3","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1161\/CIRCRESAHA.120.316101","volume":"126","author":"ME Pich\u00e9","year":"2020","unstructured":"Pich\u00e9 ME, Tchernof A, Despr\u00e9s JP. Obesity phenotypes, diabetes, and cardiovascular diseases. Circ Res. 2020;126:1477\u2013500.","journal-title":"Circ Res"},{"key":"2007_CR4","doi-asserted-by":"publisher","DOI":"10.1111\/obr.12991","volume":"21","author":"BT Tam","year":"2020","unstructured":"Tam BT, Morais JA, Santosa S. Obesity and ageing: two sides of the same coin. Obes Rev. 2020;21:e12991.","journal-title":"Obes Rev"},{"key":"2007_CR5","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1038\/ijo.2017.29","volume":"41","author":"S Stenholm","year":"2017","unstructured":"Stenholm S, Head J, Aalto V, Kivim\u00e4ki M, Kawachi I, Zins M, et al. Body mass index as a predictor of healthy and disease-free life expectancy between ages 50 and 75: a multicohort study. Int J Obes. 2017;41:769\u201375.","journal-title":"Int J Obes"},{"key":"2007_CR6","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1038\/s41580-020-00313-x","volume":"22","author":"AJ Covarrubias","year":"2020","unstructured":"Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2020;22:119\u201341.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2007_CR7","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1038\/s41392-022-01257-8","volume":"7","author":"QJ Wu","year":"2022","unstructured":"Wu QJ, Zhang TN, Chen HH, Yu XF, Lv JL, Liu YY, et al. The sirtuin family in health and disease. Signal Transduct Target Ther. 2022;7:402.","journal-title":"Signal Transduct Target Ther"},{"key":"2007_CR8","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.cmet.2012.06.016","volume":"16","author":"P Bai","year":"2012","unstructured":"Bai P, Cant\u00f3 C. The role of PARP-1 and PARP-2 enzymes in metabolic regulation and disease. Cell Metab. 2012;16:290\u20135.","journal-title":"Cell Metab"},{"key":"2007_CR9","first-page":"1","volume":"5","author":"N Xie","year":"2020","unstructured":"Xie N, Zhang L, Gao W, Huang C, Huber PE, Zhou X, et al. NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential. Signal Transduct Target Ther. 2020;5:1\u201337.","journal-title":"Signal Transduct Target Ther"},{"key":"2007_CR10","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/j.redox.2017.02.011","volume":"12","author":"R Jokinen","year":"2017","unstructured":"Jokinen R, Pirnes-Karhu S, Pietil\u00e4inen KH, Pirinen E. Adipose tissue NAD+-homeostasis, sirtuins and poly(ADP-ribose) polymerases\u2014important players in mitochondrial metabolism and metabolic health. Redox Biol. 2017;12:246\u201363.","journal-title":"Redox Biol"},{"key":"2007_CR11","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2021.100226","volume":"2","author":"BW van der Kolk","year":"2021","unstructured":"van der Kolk BW, Saari S, Lovric A, Arif M, Alvarez M, Ko A, et al. Molecular pathways behind acquired obesity: adipose tissue and skeletal muscle multiomics in monozygotic twin pairs discordant for BMI. Cell Rep Med. 2021;2:100226.","journal-title":"Cell Rep Med"},{"key":"2007_CR12","first-page":"582","volume":"13","author":"V Mart\u00ednez-Jim\u00e9nez","year":"2019","unstructured":"Mart\u00ednez-Jim\u00e9nez V, Cortez-Espinosa N, Rodr\u00edguez-Varela E, Vega-C\u00e1rdenas M, Briones-Espinoza M, Ru\u00edz-Rodr\u00edguez VM, et al. Altered levels of sirtuin genes (SIRT1, SIRT2, SIRT3 and SIRT6) and their target genes in adipose tissue from individual with obesity. Diab Metab Syndrome Clin Res Rev. 2019;13:582\u20139.","journal-title":"Diab Metab Syndrome Clin Res Rev"},{"key":"2007_CR13","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1210\/jc.2015-3054","volume":"101","author":"E Rappou","year":"2016","unstructured":"Rappou E, Jukarainen S, Rinnankoski-Tuikka R, Kaye S, Heinonen S, Hakkarainen A, et al. Weight loss is associated with increased NAD(+)\/SIRT1 expression but reduced PARP activity in white adipose tissue. J Clin Endocrinol Metab. 2016;101:1263\u201373.","journal-title":"J Clin Endocrinol Metab"},{"key":"2007_CR14","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1210\/jc.2015-3095","volume":"101","author":"S Jukarainen","year":"2016","unstructured":"Jukarainen S, Heinonen S, R\u00e4m\u00f6 JT, Rinnankoski-Tuikka R, Rappou E, Tummers M, et al. Obesity is associated with low NAD(+)\/SIRT pathway expression in adipose tissue of BMI-discordant monozygotic twins. J Clin Endocrinol Metab. 2016;101:275\u201383.","journal-title":"J Clin Endocrinol Metab"},{"key":"2007_CR15","doi-asserted-by":"publisher","first-page":"1635","DOI":"10.1038\/ijo.2016.131","volume":"40","author":"A Kurylowicz","year":"2016","unstructured":"Kurylowicz A, Owczarz M, Polosak J, Jonas MI, Lisik W, Jonas M, et al. SIRT1 and SIRT7 expression in adipose tissues of obese and normal-weight individuals is regulated by microRNAs but not by methylation status. Int J Obes. 2016;40:1635\u201342.","journal-title":"Int J Obes"},{"key":"2007_CR16","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/j.diabres.2013.07.002","volume":"101","author":"YS Song","year":"2013","unstructured":"Song YS, Lee SK, Jang YJ, Park HS, Kim JH, Lee YJ, et al. Association between low SIRT1 expression in visceral and subcutaneous adipose tissues and metabolic abnormalities in women with obesity and type 2 diabetes. Diab Res Clin Pr. 2013;101:341\u20138.","journal-title":"Diab Res Clin Pr"},{"key":"2007_CR17","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s13098-021-00623-w","volume":"13","author":"R Ferraz-Bannitz","year":"2021","unstructured":"Ferraz-Bannitz R, Welendorf CR, Coelho PO, Salgado W, Nonino CB, Beraldo RA, et al. Bariatric surgery can acutely modulate ER-stress and inflammation on subcutaneous adipose tissue in non-diabetic patients with obesity. Diabetol Metab Syndr. 2021;13:19.","journal-title":"Diabetol Metab Syndr"},{"key":"2007_CR18","doi-asserted-by":"publisher","first-page":"17312","DOI":"10.1074\/jbc.M117.778720","volume":"292","author":"S Kwon","year":"2017","unstructured":"Kwon S, Seok S, Yau P, Li X, Kemper B, Kemper JK. Obesity and aging diminish sirtuin 1 (SIRT1)-mediated deacetylation of SIRT3, leading to hyperacetylation and decreased activity and stability of SIRT3. J Biol Chem. 2017;292:17312\u201323.","journal-title":"J Biol Chem"},{"key":"2007_CR19","doi-asserted-by":"publisher","first-page":"927","DOI":"10.14336\/AD.2019.0820","volume":"11","author":"L Zhao","year":"2020","unstructured":"Zhao L, Cao J, Hu K, He X, Yun D, Tong T, et al. Sirtuins and their biological relevance in aging and age-related diseases. Aging Dis. 2020;11:927.","journal-title":"Aging Dis"},{"key":"2007_CR20","doi-asserted-by":"publisher","first-page":"16017.","DOI":"10.1038\/npjamd.2016.17","volume":"2","author":"SI Imai","year":"2016","unstructured":"Imai SI, Guarente L. It takes two to tango: NAD + and sirtuins in aging\/longevity control. NPJ Aging Mech Dis. 2016;2:16017.","journal-title":"NPJ Aging Mech Dis"},{"key":"2007_CR21","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1017\/thg.2019.106","volume":"22","author":"M Kaidesoja","year":"2019","unstructured":"Kaidesoja M, Aaltonen S, Bogl LH, Heikkil\u00e4 K, Kaartinen S, Kujala UM, et al. FinnTwin16: a longitudinal study from age 16 of a population-based Finnish Twin Cohort. Twin Res Hum Genet. 2019;22:530\u20139.","journal-title":"Twin Res Hum Genet"},{"key":"2007_CR22","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1017\/thg.2019.83","volume":"22","author":"RJ Rose","year":"2019","unstructured":"Rose RJ, Salvatore JE, Aaltonen S, Barr PB, Bogl LH, Byers HA, et al. FinnTwin12 Cohort: an updated review. Twin Res Hum Genet. 2019;22:302\u201311.","journal-title":"Twin Res Hum Genet"},{"key":"2007_CR23","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1017\/thg.2019.54","volume":"22","author":"J Kaprio","year":"2019","unstructured":"Kaprio J, Bollepalli S, Buchwald J, Iso-Markku P, Korhonen T, Kovanen V, et al. The older Finnish Twin Cohort\u201445 years of follow-up. Twin Res Hum Genet. 2019;22:240\u201354.","journal-title":"Twin Res Hum Genet"},{"key":"2007_CR24","doi-asserted-by":"crossref","unstructured":"Baecke JAH, Burema J, Frijters ER. Baecke questionnaire for measurement of a Person\u2019s habitual physical activity. In: Determinants of body fatness in young adults living in a Dutch Community Am J Clin Nutr. 1982;36:936-42.","DOI":"10.1093\/ajcn\/36.5.936"},{"key":"2007_CR25","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/0895-4356(88)90088-1","volume":"41","author":"J Kaprio","year":"1988","unstructured":"Kaprio J, Koskenvuo M. A prospective study of psychological and socioeconomic characteristics, health behavior and morbidity in cigarette smokers prior to quitting compared to persistent smokers and non-smokers. J Clin Epidemiol. 1988;41:139\u201350.","journal-title":"J Clin Epidemiol"},{"key":"2007_CR26","doi-asserted-by":"publisher","first-page":"eadd5163.","DOI":"10.1126\/sciadv.add5163","volume":"9","author":"HAK Lapatto","year":"2023","unstructured":"Lapatto HAK, Kuusela M, Heikkinen A, Muniandy M, van der Kolk BW, Gopalakrishnan S. Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study. Sci Adv. 2023;9:eadd5163.","journal-title":"Sci Adv"},{"key":"2007_CR27","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-023-01594-7","volume":"15","author":"E Sehovic","year":"2023","unstructured":"Sehovic E, Zellers SM, Youssef MK, Heikkinen A, Kaprio J, Ollikainen M. DNA methylation sites in early adulthood characterised by pubertal timing and development: a twin study. Clin Epigenetics. 2023;15:181.","journal-title":"Clin Epigenetics"},{"key":"2007_CR28","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/s42255-019-0161-5","volume":"2","author":"E Katsyuba","year":"2020","unstructured":"Katsyuba E, Romani M, Hofer D, Auwerx J. NAD+ homeostasis in health and disease. Nat Metab. 2020;2:9\u201331.","journal-title":"Nat Metab"},{"key":"2007_CR29","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1007\/s00125-019-4831-3","volume":"62","author":"NJ Connell","year":"2019","unstructured":"Connell NJ, Houtkooper RH, Schrauwen P. NAD+ metabolism as a target for metabolic health: have we found the silver bullet?. Diabetologia. 2019;62:888\u201399.","journal-title":"Diabetologia"},{"key":"2007_CR30","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.ceb.2008.03.012","volume":"20","author":"JN Feige","year":"2008","unstructured":"Feige JN, Johan A. Transcriptional targets of sirtuins in the coordination of mammalian physiology. Curr Opin Cell Biol. 2008;20:303\u20139.","journal-title":"Curr Opin Cell Biol"},{"key":"2007_CR31","doi-asserted-by":"crossref","unstructured":"Houtkooper RH, Pirinen E, Auwerx J. Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol. 2012;13:225\u201338.","DOI":"10.1038\/nrm3293"},{"key":"2007_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2020.113219","volume":"327","author":"BA Harlan","year":"2020","unstructured":"Harlan BA, Killoy KM, Pehar M, Liu L, Auwerx J, Vargas MR. Evaluation of the NAD+ biosynthetic pathway in ALS patients and effect of modulating NAD+ levels in hSOD1-linked ALS mouse models. Exp Neurol. 2020;327:113219.","journal-title":"Exp Neurol"},{"key":"2007_CR33","doi-asserted-by":"publisher","DOI":"10.5936\/csbj.201301012","volume":"4","author":"SA Trammell","year":"2013","unstructured":"Trammell SA, Brenner C. Targeted, LCMS-based metabolomics for quantitative measurement of NAD(+) metabolites. Comput Struct Biotechnol J. 2013;4:e201301012.","journal-title":"Comput Struct Biotechnol J"},{"key":"2007_CR34","doi-asserted-by":"publisher","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","volume":"51","author":"D Szklarczyk","year":"2023","unstructured":"Szklarczyk D, Kirsch R, Koutrouli M, Nastou K, Mehryary F, Hachilif R, et al. The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res. 2023;51:D638\u201346.","journal-title":"Nucleic Acids Res"},{"key":"2007_CR35","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43:e47.","journal-title":"Nucleic Acids Res"},{"key":"2007_CR36","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2020.111215","volume":"187","author":"C Chen","year":"2020","unstructured":"Chen C, Zhou M, Ge Y, Wang X. SIRT1 and aging related signaling pathways. Mech Ageing Dev. 2020;187:111215.","journal-title":"Mech Ageing Dev"},{"key":"2007_CR37","doi-asserted-by":"crossref","unstructured":"Ummarino S, Hausman C, Gaggi G, Rinaldi L, Bassal MA, Zhang Y. NAD modulates DNA methylation and cell differentiation. Cells. 2021;10:2986.","DOI":"10.3390\/cells10112986"},{"key":"2007_CR38","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1111\/dom.12171","volume":"15","author":"S Imai","year":"2013","unstructured":"Imai S, Yoshino J. The importance of NAMPT\/NAD\/SIRT1 in the systemic regulation of metabolism and ageing. Diab Obes Metab. 2013;15:26\u201333.","journal-title":"Diab Obes Metab"},{"key":"2007_CR39","doi-asserted-by":"crossref","unstructured":"Zhai X, Dang L, Wang S, Sun C. The SIRT5-mediated upregulation of C\/EBP\u03b2 promotes white adipose tissue browning by enhancing UCP1 signaling. Int J Mol Sci. 2024;25:10514.","DOI":"10.3390\/ijms251910514"},{"key":"2007_CR40","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.2337\/db18-1103","volume":"68","author":"L Shuai","year":"2019","unstructured":"Shuai L, Zhang LN, Li BH, Tang CL, Wu LY, Li J, et al. SIRT5 regulates brown adipocyte differentiation and browning of subcutaneous white adipose tissue. Diabetes. 2019;68:1449\u201361.","journal-title":"Diabetes"},{"key":"2007_CR41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-021-87759-x","volume":"11","author":"Y Majeed","year":"2021","unstructured":"Majeed Y, Halabi N, Madani AY, Engelke R, Bhagwat AM, Abdesselem H, et al. SIRT1 promotes lipid metabolism and mitochondrial biogenesis in adipocytes and coordinates adipogenesis by targeting key enzymatic pathways. Sci Rep. 2021;11:1\u201319.","journal-title":"Sci Rep"},{"key":"2007_CR42","doi-asserted-by":"publisher","first-page":"763","DOI":"10.3390\/cells13090763","volume":"13","author":"C Iacobini","year":"2024","unstructured":"Iacobini C, Vitale M, Haxhi J, Menini S, Pugliese G. Impaired remodeling of white adipose tissue in obesity and aging: from defective adipogenesis to adipose organ dysfunction. Cells. 2024;13:763.","journal-title":"Cells"},{"key":"2007_CR43","doi-asserted-by":"publisher","first-page":"164","DOI":"10.4093\/dmj.2022.0270","volume":"47","author":"EJ Bae","year":"2023","unstructured":"Bae EJ, Park BH. Multiple roles of sirtuin 6 in adipose tissue inflammation. Diab Metab J. 2023;47:164\u201372.","journal-title":"Diab Metab J"},{"key":"2007_CR44","first-page":"739","volume":"9","author":"X Li","year":"2021","unstructured":"Li X, Liu L, Li T, Liu M, Wang Y, Ma H, et al. SIRT6 in senescence and aging-related cardiovascular diseases. Front Cell Dev Biol. 2021;9:739.","journal-title":"Front Cell Dev Biol"},{"key":"2007_CR45","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1016\/j.cell.2013.06.016","volume":"154","author":"L Mouchiroud","year":"2013","unstructured":"Mouchiroud L, Houtkooper RH, Moullan N, Katsyuba E, Ryu D, Cant\u00f3 C, et al. The NAD+\/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell. 2013;154:430.","journal-title":"Cell"},{"key":"2007_CR46","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/321653","volume":"2012","author":"A Mangerich","year":"2012","unstructured":"Mangerich A, B\u00fcrkle A. Pleiotropic cellular functions of PARP1 in longevity and aging: genome maintenance meets inflammation. Oxid Med Cell Longev. 2012;2012:321653.","journal-title":"Oxid Med Cell Longev"},{"key":"2007_CR47","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.1111\/febs.15716","volume":"289","author":"K Mao","year":"2022","unstructured":"Mao K, Zhang G. The role of PARP1 in neurodegenerative diseases and aging. FEBS J. 2022;289:2013\u201324.","journal-title":"FEBS J"},{"key":"2007_CR48","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1002\/jcsm.12178","volume":"8","author":"K Boengler","year":"2017","unstructured":"Boengler K, Kosiol M, Mayr M, Schulz R, Rohrbach S. Mitochondria and ageing: role in heart, skeletal muscle and adipose tissue. J Cachexia Sarcopenia Muscle. 2017;8:349\u201369.","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"2007_CR49","doi-asserted-by":"publisher","first-page":"2622","DOI":"10.3390\/ijms19092622","volume":"19","author":"J Krstic","year":"2018","unstructured":"Krstic J, Reinisch I, Schupp M, Schulz TJ, Prokesch A. p53 functions in adipose tissue metabolism and homeostasis. Int J Mol Sci. 2018;19:2622.","journal-title":"Int J Mol Sci"},{"key":"2007_CR50","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1448535","volume":"15","author":"X Li","year":"2024","unstructured":"Li X, Li Y, Hao Q, Jin J, Wang Y. Metabolic mechanisms orchestrated by Sirtuin family to modulate inflammatory responses. Front Immunol. 2024;15:1448535.","journal-title":"Front Immunol"},{"key":"2007_CR51","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1038\/ijo.2015.221","volume":"40","author":"KH Pietilinen","year":"2015","unstructured":"Pietilinen KH, Ismail K, Jrvinen E, Heinonen S, Tummers M, Bollepalli S, et al. DNA methylation and gene expression patterns in adipose tissue differ significantly within young adult monozygotic BMI-discordant twin pairs. Int J Obes. 2015;40:654\u201361.","journal-title":"Int J Obes"},{"key":"2007_CR52","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2021.106031","volume":"137","author":"M Ma\u0142odobra-Mazur","year":"2021","unstructured":"Ma\u0142odobra-Mazur M, Cierzniak A, Myszczyszyn A, Kaliszewski K, Dobosz T. Histone modifications influence the insulin-signaling genes and are related to insulin resistance in human adipocytes. Int J Biochem Cell Biol. 2021;137:106031.","journal-title":"Int J Biochem Cell Biol"},{"key":"2007_CR53","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1111\/joim.13528","volume":"292","author":"S Lundgren","year":"2022","unstructured":"Lundgren S, Kuitunen S, Pietil\u00e4inen KH, Hurme M, K\u00e4h\u00f6nen M, M\u00e4nnist\u00f6 S, et al. BMI is positively associated with accelerated epigenetic aging in twin pairs discordant for body mass index. J Intern Med. 2022;292:627\u201340.","journal-title":"J Intern Med"},{"key":"2007_CR54","doi-asserted-by":"crossref","unstructured":"De Toro-Mart\u00edn J, Gu\u00e9nard F, Tchernof A, Hould FS, Lebel S, Julien F, et al. Body mass index is associated with epigenetic age acceleration in the visceral adipose tissue of subjects with severe obesity. Clin Epigenetics. 2019;11:172.","DOI":"10.1186\/s13148-019-0754-6"},{"key":"2007_CR55","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2025.156241","volume":"168","author":"RA Moldovan","year":"2025","unstructured":"Moldovan RA, Hidalgo MR, Casta\u00f1\u00e9 H, Jim\u00e9nez-Franco A, Joven J, Burks DJ, et al. Landscape of sex differences in obesity and type 2 diabetes in subcutaneous adipose tissue: a systematic review and meta-analysis of transcriptomics studies. Metabolism. 2025;168:156241.","journal-title":"Metabolism"},{"key":"2007_CR56","first-page":"1347","volume":"14","author":"MJ Briones-Espinoza","year":"2020","unstructured":"Briones-Espinoza MJ, Cort\u00e9s-Garc\u00eda JD, Vega-C\u00e1rdenas M, Uresti-Rivera EU, G\u00f3mez-Otero A, L\u00f3pez-L\u00f3pez N, et al. Decreased levels and activity of Sirt1 are modulated by increased miR-34a expression in adipose tissue mononuclear cells from subjects with overweight and obesity: a pilot study. Diab Metab Syndrome Clin Res Rev. 2020;14:1347\u201354.","journal-title":"Diab Metab Syndrome Clin Res Rev"},{"key":"2007_CR57","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.freeradbiomed.2012.10.525","volume":"56","author":"BJ Morris","year":"2013","unstructured":"Morris BJ. Seven sirtuins for seven deadly diseases of aging. Free Radic Biol Med. 2013;56:133\u201371.","journal-title":"Free Radic Biol Med"},{"key":"2007_CR58","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1007\/s12020-018-1544-1","volume":"60","author":"M Stefanowicz","year":"2018","unstructured":"Stefanowicz M, Niko\u0142ajuk A, Matulewicz N, Karczewska-Kupczewska M. Adipose tissue, but not skeletal muscle, sirtuin 1 expression is decreased in obesity and related to insulin sensitivity. Endocrine. 2018;60:263\u201371.","journal-title":"Endocrine"},{"key":"2007_CR59","doi-asserted-by":"crossref","unstructured":"Heinonen S, Jokinen R, Rissanen A, Pietil\u00e4inen KH. White adipose tissue mitochondrial metabolism in health and in obesity. Obes Rev. 2020;21:e12958.","DOI":"10.1111\/obr.12958"}],"container-title":["International Journal of Obesity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41366-025-02007-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41366-025-02007-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41366-025-02007-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T13:02:25Z","timestamp":1775566945000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41366-025-02007-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,5]]},"references-count":59,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["2007"],"URL":"https:\/\/doi.org\/10.1038\/s41366-025-02007-w","relation":{},"ISSN":["0307-0565","1476-5497"],"issn-type":[{"value":"0307-0565","type":"print"},{"value":"1476-5497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,5]]},"assertion":[{"value":"21 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 December 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 December 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 January 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}