Painful diabetic neuropathy is associated with accelerated epigenetic aging

• DOI: 10.1007/s11357-025-01516-w
• Publication Date: 2025-01-23T04:52:18Z
• Authors: Katarzyna Malgorz...; Paolo Garagnani; Massimiliano Bonafé; Maria Giulia Baca...; Luciano Calzari; Davide Gentilini; Dan Ziegler; Monique M. Gerrits; Catharina G. Faber; Rayaz A. Malik; Margherita Marchi; Erika Salvi; Giuseppe Lauria; Chiara Pirazzini
• Keywords: dNaM; Premature aging

Abstract About one out of two diabetic patients develop neuropathy (DN), these 20% experience neuropathic pain (NP) leading to individual, social, and health-economic burden. Risk factors for NP are largely unknown; however, premature aging was recently associated with several chronic disorders. DNA methylation-based biological age (DNAm) is disease risk, morbidity, mortality in different clinical settings. The purpose this work study, the first time, whether involved development a huge cohort DN assessed by anatomopathological assay (99 painful (PDN), 132 painless (PLDN) patients, 84 controls (CTRL)). Six subsets DNAm biomarkers were calculated evaluate NP-associated changes epigenetic aging, telomere shortening, blood cell count estimates, plasma protein surrogates. We observed pain-related acceleration (DNAmAgeHannum, DNAmGrimAgeBasedOnPredictedAge, DNAmAgeSkinBloodClock), pace (DunedinPoAm), shortening telomeres between PDN PLDN patients. showed decreased predicted counts B lymphocytes, naive absolute CD8 T cells, increased granulocyte counts. Several surrogates proteins significantly (GHR, MMP1, THBS2, PAPPA, TGF-α, GDF8, EDA, MPL, CCL21) PDNs compared PLDNs. These results provide evidence an DN. This achievement has been possible thanks state art phenotyping enrolled Our findings indicate that process may be directly progression general health degeneration T2DM Therefore, it hypothesize administration effective antiaging drugs could slow down or even block advancement.