Abstract
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.
Highlights
Recent attention has focused on discovering new biomarkers that may serve as indicators of both health span and life span
LncRNAs have been studied in the context of senescence and various other hallmarks of aging, little is known about whether long noncoding RNAs (lncRNAs) expression is altered with human age
If we categorize based on race, poverty and age, we identified changes in lncRNA levels that occurred with both races comparing above and below poverty status
Summary
Recent attention has focused on discovering new biomarkers that may serve as indicators of both health span and life span. Recent findings from model systems suggest that longevity and health span can be modulated by specific changes in gene expression patterns [10, 16] These patterns could be useful markers for identifying individuals in at-risk populations for the premature development of disease or monitoring adverse outcomes that may lead to early mortality. The observed increase in mRNAs encoding inflammatory proteins and the decrease in mRNAs encoding immune-response proteins, termed the Conserved Transcriptional Response to Adversity (CTRA) [25,26,27], has been documented in several human and non-human models (for review [28]) These data hint that differences in gene expression may underlie racial and socioeconomic disparities in health. LncRNAs may be important promoters of the change in gene expression that results from exposure to various social-environmental conditions
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