Effect of Aging on the Plasma Membrane Repair Process in Multiple Cell Types

Abstract

Plasma membrane repair mechanisms play a vital role in supporting the structure and function of most mammalian cells by preventing changes in the permeability of the cell membrane and maintaining its barrier function1. Breakdown of the barrier function of the membrane can lead to death of the cell and accumulation (or prevention) of such cell death events can contribute to the progression of various diseases, including cancer2, bacterial infection3, Alzheimer's disease4,5, heart failure6,7 and various inherited myopathies such as Duchenne muscular dystrophy8. Many of these disease states are also exacerbated by the aging process which can alter intracellular vesicle trafficking9, a process that is essential for effective plasma membrane repair10–12. Here we tested the hypothesis that during the aging process the membrane repair capacity of multiple cell types decreases. We first determined if membrane repair efficiency changed in Mus musculus muscle tissue cells (myocytes) from young or aged mice using laser microscopy injury to determine the effectiveness of plasma membrane repair 13. Further experimentation was conducted on the effects of senescence, or premature aging, on primary human fibroblasts from young volunteers. Fibroblast cells were cultured and treated with hydroxyurea, which causes growth arrest in the S phase of the cell cycle, every 72 hours for 12 days 14. Membrane repair capacity was measured using laser microscopy on senescent cells compared to young untreated control cells. Preliminary findings show a decrease in membrane repair capacity in cells with induced senescence, however, this change does not reach a statistically significant level in those cells treated with hydroxyurea 14. Results of this experiment will guide future research to determine the mechanism of reduced membrane repair during aging in M. musculus cells and determine if this process affects primary human fibroblast cells. Future investigation in the membrane repair process will include locating a potential therapeutic target for aging-related diseases.