# OVCH1 Antisense RNA 1 is differentially expressed between non-frail and frail old adults

## TL;DR

This study finds that OVCH1 Antisense RNA 1 is expressed differently in non-frail and frail older adults, suggesting a potential role in age-related health differences.

## Contribution

The study identifies OVCH1 Antisense RNA 1 as a differentially expressed RNA in frailty and explores its potential role in age-related health decline.

## Key findings

- OVCH1 Antisense RNA 1 and other lncRNAs like XIST and TTTY14 are differentially expressed between non-frail and frail older adults.
- Glycogen Phosphorylase L (PYGL) is a top hub gene associated with frailty and non-frailty differences.
- Transcription factors FOXO3 and MYC show distinct expression patterns linked to age-related pathways in non-frail and frail individuals.

## Abstract

While some old adults stay healthy and non-frail up to late in life, others experience multimorbidity and frailty often accompanied by a pro-inflammatory state. The underlying molecular mechanisms for those differences are still obscure. Here, we used gene expression analysis to understand the molecular underpinning between non-frail and frail individuals in old age. Twenty-four adults (50% non-frail and 50% frail) from InCHIANTI study were included. Total RNA extracted from whole blood was analyzed by Cap Analysis of Gene Expression (CAGE). CAGE identified transcription start site (TSS) and active enhancer regions. We identified a set of differentially expressed (DE) TSS and enhancer between non-frail and frail and male and female participants. Several DE TSSs were annotated as lncRNA (XIST and TTTY14) and antisense RNAs (ZFX-AS1 and OVCH1 Antisense RNA 1). The promoter region chr6:366,786,54-366,787,97;+ was DE and overlapping the longevity CDKN1A gene. GWAS-LD enrichment analysis identifies overlapping LD-blocks with the DE regions with reported traits in GWAS catalog (isovolumetric relaxation time and urinary tract infection frequency). Furthermore, we used weighted gene co-expression network analysis (WGCNA) to identify changes of gene expression associated with clinical traits and identify key gene modules. We performed functional enrichment analysis of the gene modules with significant trait/module correlation. One gene module is showing a very distinct pattern in hub genes. Glycogen Phosphorylase L (PYGL) was the top ranked hub gene between non-frail and frail. We predicted transcription factor binding sites (TFBS) and motif activity. TF involved in age-related pathways (e.g., FOXO3 and MYC) shows different expression patterns between non-frail and frail participants. Expanding the study of OVCH1 Antisense RNA 1 and PYGL may help understand the mechanisms leading to loss of homeostasis that ultimately causes frailty.

The online version contains supplementary material available at 10.1007/s11357-023-00961-9.