Major and Classification
Bachelor of Science in Human Development and Aging & Minor in Hip-Hop
Faculty Mentor
Dr. Tara Mastro, PhD, Department of Gerontology
Department
USC Leonard Davis School of Gerontology
Research Gateway Project
A Multi-omic Characterization of Human Fibroblasts Overexpressing Alu
Project Abstract
For decades, a significant portion of our genome consisting of repetitive DNA, including transposable elements (TEs), was relegated to the realm of “junk” or “selfish” DNA. Astonishingly, it is estimated that approximately 45% of the human genome is comprised of transposable elements. Genomic instability, often observed during aging and in age-related diseases like cancer, is now understood to be linked with the activity of TEs (Rodriguez et al., 2020). In the United States, cancer alone accounts for a substantial disease burden, with over 600,000 (American Cancer Society, 2021) deaths annually. Understanding the regulatory mechanisms and functional consequences of TEs, therefore, has the potential to create life-saving treatments.
TEs are DNA sequences that have the ability to move from different locations in the genome. Transposons can be classified as Class I and Class II. Class I transposons, or retrotransposons, use a “copy and paste” mechanism to move around the genome. Class II transposons, in contrast, use a “cut and paste” mechanism to move around the genome (Well et al., 2020). In humans, the most active and abundant TEs are Long interspersed element 1 (LINE-1; L1) and Alu. L1 is a family of autonomous, actively mobile retrotransposons that occupy ∼17% of the human genome (Lander et al., 2001, Venter et al., 2001). Alu elements, similarly, are retrotransposons that make up around ~11% of the genome (Lander et al., 2001, Venter et al., 2001), though they are non-autonomous and rely on L1 for their mobility (Bravo et al., 2023).
During aging, TEs can become derepressed, leading to increased transcription of TE-related RNA (Bravo et al., 2020). This derepression can result in the mobilization of TE copies, leading to the generation of additional copies of these elements within the genome (Bravo et al., 2020). It has been mostly unclear whether TEs are simply bystanders during aging or whether they contribute to, and drive, aging and aging-related diseases. Over the past few years, however, researchers have demonstrated that TEs can promote various aspects of aging, including genomic instability, inflammation, and mitochondrial dysfunction (Bravo et al., 2020). However, the full list of aging hallmarks modified in response to alterations in transposon levels remains incomplete.