Intron retention in aging and Alzheimer’s disease (AD): AD is an age-related neurodegenerative disorder with pathological accumulation of amyloid plaque (Masters et al., 2015), which can be classified into familial and sporadic form. In familial AD, mutations in genes encod-ing either amyloid precursor protein or presenilin (PS1 and PS2) cause overproduction of amyloid-42 molecules and early onset of dementia. Late-onset sporadic AD, which accounts for majority of the cases (>95%), is characterized by high degree of genetic and pathological het-erogeneity. Although aging and genetic variants are two risks factors for sporadic AD, it remains unclear how epigenetic alterations during aging may contribute to its etiology. To determine the transcriptional changes that are associated with aging, we analyzed the transcriptome of head or brain tissues isolated at different ages from adult Drosophila, mice and human (Adusumalli et al., 2019). We observed an increase in the level of intron retention (IR) in the mRNA transcripts during aging across different species. These retained introns share highly conserved features and surprisingly, do not affect the expression level of their mRNA transcripts. As many age-dependent IR mRNA transcripts over-lapped with curated AD genes, we further compared the IR patts in the frontal cortex and cerebellum isolated from large AD cohorts with their age-matched controls. Consistent with reports of aberrant splicing in AD (Tollervey et al., 2011; Bai et al., 2013; Raj et al., 2018), we found a significant increase in the rate of IR at genes that are involved in RNA processing and protein homeostasis in AD samples. Furthermore, many of these IR genes showed significant changes in their protein levels when compared to age-matched controls. Taken together, our findings suggest that increased IR is a transcriptional signature that is conserved across species during aging and may be linked to AD progression.