Epigenetic factors and inflammaging: FOXO3A as a potential biomarker of sarcopenia and upregulation of DNMT3A and SIRT3 in older adults

• Published in: Frontiers in immunology Vol. 16; p. 1467308
• Main Authors: Bogucka, Diana, Wajda, Anna, Stypińska, Barbara, Radkowski, Marcin Jerzy, Targowski, Tomasz, Modzelewska, Ewa, Kmiołek, Tomasz, Ejma-Multański, Adam, Filipowicz, Gabriela, Kaliberda, Yana, Dudek, Ewa, Paradowska-Gorycka, Agnieszka
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 2025
• Subjects: Adult; Aged; Aged, 80 and over; ageing; DNA Methyltransferase 3A - genetics; Epigenesis, Genetic; Female; Forkhead Box Protein O3 - genetics; FOXO3A; frailty; Genetic Markers; geriatrics; Humans; Immunology; inflammation; Male; Middle Aged; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; RNA, Messenger - genetics; sarcopenia; Sarcopenia - genetics; Sarcopenia - pathology; Sirtuin 3 - genetics; Up-Regulation; frailty; geriatrics; ageing; inflammation; DNMT3A; FOXO3A; SIRT3; sarcopenia
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2025.1467308

Epigenetic factors influence inflammaging and geriatric disorders such as sarcopenia and frailty. It is necessary to develop a biomarker/panel of biomarkers for fast and easy diagnostics. Currently, hard-to-access equipment is required to diagnose sarcopenia. The development of a biomarker/panel of biomarkers will prevent many older adults from being excluded from the diagnostic process. In this study, we analyzed selected gene expression profiles, namely, , , , , , , and , in whole blood. The study included 168 subjects divided into five groups: patients hospitalized at the Geriatrics Clinic and Polyclinic with sarcopenia, frailty syndrome, or without those disorders (geriatric control), and non-hospitalized healthy controls (HC) aged 25 to 30 years and over 50 years. We revealed a lower mRNA level of (p<0.001) in sarcopenic patients compared to the geriatric controls. Furthermore, we detected upregulation of (p=0.003) and (p=0.015) in HC over 50 years old compared to HC aged 25 to 30 years. Interestingly, we observed 2 cluster formations during the gene expression correlation analysis ( , , , and , ). We also noted correlations of clinical parameters with mRNA levels in the sarcopenic patients group, such as vitamin D level with (r=0.64, p=0.010), creatine kinase with (r=-0.58, p=0.032) and (r=-0.59, p=0.026), creatinine with (r=0.57, p=0.026), erythrocyte sedimentation rate (ESR) with (r=0.69, p=0.004), and lactate dehydrogenase (LDH) with (r=-0.86, p=0.007). In the frailty syndrome group, we noted a correlation of appendicular skeletal muscle mass (ASMM) with (r=0.59, p=0.026) mRNA level. In the geriatric controls, we observed a correlation of serum iron with mRNA level (r=-0.79, p=0.036). Our study revealed as a potential biomarker of sarcopenia. Furthermore, we observed a high expression of epigenetic factors ( and ) in older adults.