4-N-furfurylcytosine, a novel cytosine-derived modulator of mitochondrial and redox homeostasis to counteract aging: Insights from cellular and mouse models<\/p>\n
Agnieszka Fedoruk-Wyszomirska, Pawe\u0142 Pawelczak, Marta Orlicka-P\u0142ocka, Dorota Gurda-Wo\u017ana, Ma\u0142gorzata Giel-Pietraszuk, \u0141ukasz Przyby\u0142, Grzegorz Framski, Karol Pasternak, Agata Chmurzynska, Eliza Wyszko<\/p>\n
Abstrakt<\/p>\n
Mitochondrial dysfunction and redox imbalance are key features of aging that drive cellular senescence, metabolic decline, and tissue degeneration. 4-N-furfurylcytosine (FC), a cytosine derivative with redox-modulating properties, has been proposed to counteract age-associated oxidative damage; however, its effects in mammalian aging remain unexplored. The anti-aging potential of FC was investigated using a translational approach integrating in vitro and in vivo models. Human fibroblasts (MRC-5) and keratinocytes (HaCaT) subjected to physiological and stress-induced senescence were used to assess mitochondrial function, redox balance, and proteostasis, while aged C57BL\/6J mice, long-term supplemented with FC were evaluated for systemic metabolic, molecular, and behavioral outcomes. FC enhanced cell survival and mitigated key hallmarks of senescence, including \u03b2-galactosidase activity and p16 expression. Moreover, FC reduced intracellular reactive oxygen species and oxidative damage, as evidenced by decreased levels of 8-oxodG, protein carbonyls, and lipid peroxidation. FC improved mitochondrial membrane polarization and increased ATP levels while reducing oxygen consumption, indicating an altered bioenergetic state. Proteomic profiling revealed enrichment of pathways related to mitochondrial maintenance, antioxidant defense, and proteostasis, consistent with enhanced metabolic adaptability. In aged mice, FC supplementation preserved lean body mass, improved coordination and endurance, stabilized lipid and glucose metabolism, maintained telomere integrity, increased mtDNA:nDNA ratio, and reduced systemic oxidative stress markers, indicating delayed molecular aging and preserved mitochondrial function without overt adverse effects detected in the measured readouts. 4-N-furfurylcytosine modulates redox- and mitochondria-associated aging phenotypes in cellular and mouse models, with effects consistent with remodeling of mitochondrial homeostasis and improved resilience to oxidative stress. These findings support FC as a promising candidate for further investigation as a modulator of aging-related processes.<\/p>\n
S\u0142owa kluczowe: 4-N-Furfurylcytosine; Aging; Anti-aging activity; Epigenetic regulation; Mitochondrial quality control; Redox homeostasis; Telomere maintenance<\/p>\n
Free Radical Biology and Medicine, 2026, 253:443-462; doi: 10.1016\/j.freeradbiomed.2026.05.312<\/p>\n","protected":false},"excerpt":{"rendered":"
4-N-furfurylcytosine, a novel cytosine-derived modulator of mitochondrial and redox homeostasis to counteract aging: Insights from cellular and mouse models Agnieszka Fedoruk-Wyszomirska, Pawe\u0142 Pawelczak, Marta Orlicka-P\u0142ocka, Dorota Gurda-Wo\u017ana, Ma\u0142gorzata Giel-Pietraszuk, \u0141ukasz Przyby\u0142, Grzegorz Framski, Karol Pasternak, Agata Chmurzynska, Eliza Wyszko Abstrakt… Czytaj dalej<\/a><\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[20],"tags":[],"_links":{"self":[{"href":"http:\/\/www1.up.poznan.pl\/kzcid\/wp-json\/wp\/v2\/posts\/2692"}],"collection":[{"href":"http:\/\/www1.up.poznan.pl\/kzcid\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/www1.up.poznan.pl\/kzcid\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/www1.up.poznan.pl\/kzcid\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"http:\/\/www1.up.poznan.pl\/kzcid\/wp-json\/wp\/v2\/comments?post=2692"}],"version-history":[{"count":1,"href":"http:\/\/www1.up.poznan.pl\/kzcid\/wp-json\/wp\/v2\/posts\/2692\/revisions"}],"predecessor-version":[{"id":2693,"href":"http:\/\/www1.up.poznan.pl\/kzcid\/wp-json\/wp\/v2\/posts\/2692\/revisions\/2693"}],"wp:attachment":[{"href":"http:\/\/www1.up.poznan.pl\/kzcid\/wp-json\/wp\/v2\/media?parent=2692"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/www1.up.poznan.pl\/kzcid\/wp-json\/wp\/v2\/categories?post=2692"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/www1.up.poznan.pl\/kzcid\/wp-json\/wp\/v2\/tags?post=2692"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}