{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:36:04Z","timestamp":1789428964291,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Nucleotides\u2014essential substrates for DNA repair, energy metabolism, and redox regulation\u2014are emerging as nutritional modulators of biological aging. Yet, individual responses to exogenous nucleotide (NTs) supplementation remain poorly understood. Given that urate metabolism governs systemic oxidative balance, this study investigated whether genetic variability in urate regulation modifies the anti\u2010aging effects of NTs. In this secondary analysis of the TALENTs randomized controlled trial (121 adults aged 60\u201370\u2009years; 19\u2010week intervention; NCT05243108), participants were stratified by urate polygenic risk score (UA\u2010PRS) to evaluate genotype\u2010dependent responses in DNA methylation age (DNAmAge) and leukocyte telomere length (LTL). A significant UA\u2010PRS\u2009\u00d7\u2009intervention interaction was observed for \u0394DNAmAge (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0114) and \u0394LTL (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0271). NTs supplementation reduced DNAmAge in the High\u2010PRS group (\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2009=\u2009\u22125.10,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.00013) and preserved telomere length in the Low\u2010PRS group (\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2009=\u20090.31,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0043). Multi\u2010omics analyzes revealed that NTs modulated glucose\u2010transport and pentose phosphate pathways in High\u2010PRS individuals, while enhancing immune regulation and reducing GDF15 and IL\u20101\u03b2 levels in Low\u2010PRS individuals. These findings suggest that genetic variation in urate metabolism determines whether NTs are preferentially utilized for redox and epigenetic maintenance or for immune and inflammatory regulation, supporting a precision\u2010nutrition model for delaying biological aging.\n                  <\/jats:p>","DOI":"10.1111\/acel.70581","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T03:27:42Z","timestamp":1781062062000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Urate\u2010Related Genetic Risk Modulates the Anti\u2010Aging Effects of Exogenous Nucleotides: Multi\u2010Omics Evidence From Older Adults"],"prefix":"10.1111","volume":"25","author":[{"given":"Ruisheng","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyue","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxiao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueying","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health Peking University Health Science Center  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health Peking University  Beijing China"},{"name":"Key Laboratory of Epidemiology of Major Diseases (Peking University) Ministry of Education  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health Peking University  Beijing China"},{"name":"Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meihong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health Peking University  Beijing China"},{"name":"Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety Peking University  Beijing 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