Date Published: February 28, 2019
Publisher: Impact Journals
Author(s): Nicole Noren Hooten, Michele K. Evans.
Emerging evidence indicates that noncoding RNAs play regulatory roles in aging and disease. The functional roles of long noncoding RNAs (lncRNAs) in physiology and disease are not completely understood. Little is known about lncRNAs in the context of human aging and socio-environmental conditions. Microarray profiling of lncRNAs and mRNAs from peripheral blood mononuclear cells from young and old white (n=16) and African American (AA) males (n=16) living above or below poverty from the Healthy Aging in Neighborhoods of Diversity across the Life Span study revealed changes in both lncRNAs and mRNAs with age and poverty status in white males, but not in AA males. We validated lncRNA changes in an expanded cohort (n=40); CTD-3247F14.2, GAS5, H19, TERC and MEG3 changed significantly with age, whereas AK022914,GAS5, KB-1047C11.2, MEG3 and XLOC_003262 changed with poverty. Mitochondrial function and response to DNA damage and stress were pathways enriched in younger individuals. Response to stress, viral infection, and immune signals were pathways enriched in individuals living above poverty. These data show that both human age and a marker of social adversity influence lncRNA expression, which may provide insight about molecular pathways underlying aging and social factors that affect disparities in aging and disease.
Recent attention has focused on discovering new biomarkers that may serve as indicators of both health span and life span. DNA methylation, telomere erosion, DNA damage and repair, mitochondrial copy number and function are considered markers of biological aging . However, it has been difficult to unequivocally identify a single universal biomarker to monitor aging differentiated from disease because there is considerable variation in the signs and symptoms of aging. Studies have also identified noncoding RNAs (ncRNAs), such as microRNAs (miRNAs), as relevant biomarkers of aging. We and others have shown that miRNA levels change during human aging [2–6]. Interestingly, these changes in miRNA levels can be modulated by interventions such as calorie restriction or metformin [7,8]. miRNAs are also key regulators of cellular processes important for aging such as cellular senescence . Data from model systems also support a role for miRNAs in the aging process. For example, the Caenorhabditis elegans miRNA lin-4 regulates lifespan through modulating expression of its target gene, lin-14 . Since this initial discovery several other miRNAs have been associated with regulating longevity in C. elegans .
Here, we have examined differences in expressed lncRNAs and mRNAs with age and poverty status in both white and AA males. In our initial genome-wide profiling, we found that white males had larger significant differences in expression levels of lncRNAs and mRNAs with poverty and age, as compared to AA males, where these changes were far more modest. This indicates that the influence of age and poverty on gene expression patterns differs between racial groups. It is not clear what drives these differences, but they may correlate with the wide gap in health status and health outcomes between AAs and whites particularly between AA men and white men. AA males living below poverty in the HANDLS cohort, and in other studies, are particularly vulnerable to early mortality compared to their white counterparts and even when compared to AA men who live above the poverty line despite adjustments for various lifestyle cofactors [21,22]. Given this disparity, it is important to examine whether and how gene expression or other genomic factors may act as a biologic transduction pathway for the social determinants of health.