Free Radical Biology and Medicine
Human longevity is increasing; in fact, the United States Census Bureau predicts that there will be a 10% increase in individuals 65 y of age and older by 2050. Unfortunately, increases in longevity is also associated with increased risk factors for numerous health issues, and decreased effectiveness of medical interventions. Aging cells lose their ability to renew and repair damage. RNA sequencing and bioinformatics analysis of primary cultures of Normal Human Fibroblasts (NHFs) from healthy donors of different ages (3 d – 70 y) ranked lipid metabolism as the number one metabolic process that is significantly altered during aging. Using BODIPY C11 fluorescent probes to measure ratio of lipid peroxides (LOO•) to neutral lipids, our results showed an age associated increase (up to 100%) in lipid peroxidation in 20 different NHFs aged from 17 y up to 79 y. Results from Immune blot analysis showed significant decreases (greater than 50%) in the expression of G0-G1 Switch 2 (G0S2), a negative regulator of the lipolytic enzyme, Adipose triglyceride lipase (ATGL) in older NHFs, whereas no significant difference was observed in the protein levels of fatty acid synthase (FASN) and ATGL or its co-activator Comparative Gene Identification-58 (CGI-58). Using Platypus cell migration and wound healing assay, results showed that NHFs from older individuals have slower wound closing ability when compared to NHFs from younger individuals. Over all these results indicate that a G0S2 dependent lipolytic signaling contributes to age-related impairment in wound healing via lipid peroxides. Intervention of the G0S2-ATGL lipid signaling pathway is an attractive and novel avenue to mitigate age-associated decline in the regenerative efficacy of tissues.
Pearson K, Hiremagalore S, Fussell J, Kalen A, Goswami P, Sarsour E. Decreases in G0-G1 Switch 2 Expression and Increases in Lipid Peroxidation Impaired Wound Healing in Aging Normal Human Fibroblasts. Free Radical Biology and Medicine. 2022; 180(S1).