The prediction of chronological age from methylation-based biomarkers represents one of the most promising applications in the field of forensic sciences. Age-prediction models developed so far are not easily applicable for forensic caseworkers. Among the several attempts to pursue this objective, the formulation of single-locus models might represent a good strategy. The present work aimed to develop an accurate single-locus model for age prediction exploiting ELOVL2, a gene for which epigenetic alterations are most highly correlated with age. We carried out a systematic review of different published pyrosequencing datasets in which methylation of the ELOVL2 promoter was analysed to formulate age prediction models. Nine of these, with available datasets involving 2298 participants, were selected. We found that irrespective of which model was adopted, a very strong relationship between ELOVL2 methylation levels and age exists. In particular, the model giving the best age-prediction accuracy was the gradient boosting regressor with a prediction error of about 5.5 years. The findings reported here strongly support the use of ELOVL2 for the formulation of a single-locus epigenetic model, but the inclusion of additional, non-redundant markers is a fundamental requirement to apply a molecular model to forensic applications with more robust results.

Starting in early 2008, dominant mutations in TARDBP gene have been reported by several groups as a primary cause of ALS. To date, a total of 30 mutations of TARDBP have been reported not only in SOD1-negative FALS cases (∼3%) but also in SALS cases (∼1.5%). All but one of the mutations identified (D169G) reside in exon 6 of the TARDBP gene, which encodes for the C-terminal glycine-rich domain of TDP-43. All of these mutations are dominantly inherited missense changes with the exception of a truncating mutation (Y374X) at the extreme C terminus of the protein.3

Neurodegenerative diseases are progressive disorders that affect the central nervous system (CNS) and represent the major cause of premature death in the elderly. One of the possible determinants of neurodegeneration is the change in mitochondrial function and content. Altered levels of mitochondrial DNA copy number (mtDNA-CN) in biological fluids have been reported during both the early stages and progression of the diseases. In patients affected by neurodegenerative diseases, changes in mtDNA-CN levels appear to correlate with mitochondrial dysfunction, cognitive decline, disease progression, and ultimately therapeutic interventions. In this review, we report the main results published up to April 2024, regarding the evaluation of mtDNA-CN levels in blood samples from patients affected by Alzheimer’s (AD), Parkinson’s (PD), and Huntington’s diseases (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). The aim is to show a probable link between mtDNA-CN changes and neurodegenerative disorders. Understanding the causes underlying this association could provide useful information on the molecular mechanisms involved in neurodegeneration and offer the development of new diagnostic approaches and therapeutic interventions.