Essential tremor (ET) is a common movement disorder increasingly recognized as a complex syndrome with neurodegenerative features. While mitochondrial dysfunction and cellular aging are implicated in several neurodegenerative diseases, their role in ET remains unexplored. To investigate mitochondrial DNA copy number (mtDNA-CN) and telomere length (TL) in patients with ET and evaluate their potential as biomarkers of mitochondrial dysfunction and biological aging. In this cross-sectional case–control study, 68 ET patients (median age 66 years; 64.7% male) and 62 healthy controls (median age 70 years; 54.8% male) were enrolled. Relative mtDNA-CN and TL were quantified by quantitative PCR, measuring mitochondrial ND1 gene levels and telomere-to-single-copy gene (T/S) ratio, respectively, both normalized to β-actin. Associations with disease status were assessed using age- and sex-adjusted multivariable linear regression on log2-transformed data, with statistical significance defined as p < 0.05 after false discovery rate (FDR)-corrected Wald tests. Receiver operating characteristic (ROC) and effect size (Cohen’s d) analyses were performed. ET patients showed significantly reduced mtDNA-CN (β = −2.785, 95% CI −3.700 to −1.869; pFDR = 2.53 × 10−9) and TL (β = −2.073, 95% CI −2.758 to −1.388; pFDR = 3.00 × 10−9), corresponding to ~6.9-fold and ~4.2-fold reductions, respectively. Age- and sex-stratified analyses confirmed consistent reductions, more pronounced in older individuals. Both biomarkers showed good discriminatory performance (mtDNA-CN: AUC = 0.83, 95% CI: 0.75–0.90; TL: AUC = 0.76, 95% CI: 0.68–0.85) and large effect sizes (Cohen’s d = |1.192| and |1.058|), respectively. Reduced mtDNA-CN and TL support the involvement of mitochondrial impairment and accelerated cellular aging in ET and may represent accessible peripheral biomarkers and provide a basis for future longitudinal and mechanistic investigations.
Gagliardi et al. (Wed,) studied this question.