Simultaneous assessment of mitochondrial DNA copy number and nuclear epigenetic age towards predictive models of development and aging.

OBJECTIVE: Mitochondrial dysfunction and nuclear epigenetic alterations, two hallmarks of aging, are associated with aberrant development and complex disease risk. Here, we report a method for the simultaneous assessment of mitochondrial DNA copy number (mtDNA-CN) and DNA methylation age (DNAm age) from the same DNA extraction using quantitative polymerase chain reaction (qPCR) and array data, respectively. RESULT: We present methods for the concurrent estimation of mtDNA-CN and DNAm age from the same DNA samples. This includes qPCR to estimate mtDNA-CN, representing the number of circular mitochondrial genomes in a cell, and DNA methylation microarray data to estimate the epigenetic age of an individual. Further, we provide a method for the combination of these metrics into a shared metric termed 'mtEpiAge'. This approach provides a valuable tool for exploring the interplay between mitochondrial dysfunction and nuclear epigenetic alterations, and their associations with disease and aging.

Mitochondrial genomic integrity and the nuclear epigenome in health and disease.

Bidirectional crosstalk between the nuclear and mitochondrial genomes is essential for proper cell functioning. Mitochondrial DNA copy number (mtDNA-CN) and heteroplasmy influence mitochondrial function, which can influence the nuclear genome and contribute to health and disease. Evidence shows that mtDNA-CN and heteroplasmic variation are associated with aging, complex disease, and all-cause mortality. Further, the nuclear epigenome may mediate the effects of mtDNA variation on disease. In this way, mitochondria act as an environmental biosensor translating vital information about the state of the cell to the nuclear genome. Cellular communication between mtDNA variation and the nuclear epigenome can be achieved by modification of metabolites and intermediates of the citric acid cycle and oxidative phosphorylation. These essential molecules (e.g. ATP, acetyl-CoA, ɑ-ketoglutarate and S-adenosylmethionine) act as substrates and cofactors for enzymes involved in epigenetic modifications. The role of mitochondria as an environmental biosensor is emerging as a critical modifier of disease states. Uncovering the mechanisms of these dynamics in disease processes is expected to lead to earlier and improved treatment for a variety of diseases. However, the influence of mtDNA-CN and heteroplasmy variation on mitochondrially-derived epigenome-modifying metabolites and intermediates is poorly understood. This perspective will focus on the relationship between mtDNA-CN, heteroplasmy, and epigenome modifying cofactors and substrates, and the influence of their dynamics on the nuclear epigenome in health and disease.

Individual differences in preference for epistemic versus teleologic strategies of deliberate self-persuasion.

People are often dissatisfied with their attitudes (e.g., liking their jobs too little or junk food too much) and would like to evaluate differently. On the basis of theory and research, a scale was developed to measure individual differences in preference for 2 types of cognitive tactics (epistemic or teleologic [E or T]) that people use when they try to change their own attitudes (Maio & Thomas, 2007). For each of 3 attitude objects (my life, a romantic partner, Arabs), the scale items loaded on the 2 intended factors, and E - T scale scores were significantly correlated across the 3 attitude objects (Study 1). Scale scores also displayed satisfactory internal and test-retest reliability and discriminant validity (Study 2). In addition, E - T scores (i.e., mean preference for epistemic vs. teleologic tactics) displayed satisfactory predictive and construct validity by predicting the extent to which individuals would recall negative attributes of their lives (Study 3) and of going to a counseling center (Study 4) after a session of deliberate self-persuasion. The discussion centers on theoretical and practical applications of the new scale.