Journalartikel
Autorenliste: Garcia Castro, Claudia F.; Nardiello, Claudio; Hadzic, Stefan; Kojonazarov, Baktybek; Kraut, Simone; Gierhardt, Mareike; Schäffer, Julia; Bednorz, Mariola; Quanz, Karin; Heger, Jacqueline; Korfei, Martina; Wilhelm, Jochen; Hecker, Matthias; Bartkuhn, Marek; Arnhold, Stefan; Guenther, Andreas; Seeger, Werner; Schulz, Rainer; Weissmann, Norbert; Sommer, Natascha; Pak, Oleg
Jahr der Veröffentlichung: 2024
Seiten: 911-926
Zeitschrift: Aging and Disease
Bandnummer: 15
Heftnummer: 2
ISSN: 2152-5250
Open Access Status: Gold
DOI Link: https://doi.org/10.14336/AD.2023.0715
Verlag: Buck Institute for Age Research
Abstract:
The mitochondrial adaptor protein p66Shc has been suggested to control life span in mice via the release of hydrogen peroxide. However, the role of p66Shc in lung aging remains unsolved. Thus, we investigated the effects of p66Shc-/-on the aging of the lung and pulmonary circulation. In vivo lung and cardiac characteristics were investigated in p66Shc-/-and wild type (WT) mice at 3, 12, and 24 months of age by lung function measurements, micro-computed tomography (& mu;CT), and echocardiography. Alveolar number and muscularization of small pulmonary arteries were measured by stereology and vascular morphometry, respectively. Protein and mRNA levels of senescent markers were measured by western blot and PCR, respectively. Lung function declined similarly in WT and p66Shc-/-mice during aging. However, & mu;CT analyses and stereology showed slightly enhanced signs of aging-related parameters in p66Shc-/-mice, such as a decline of alveolar density. Accordingly, p66Shc-/-mice showed higher protein expression of the senescence marker p21 in lung homogenate compared to WT mice of the corresponding age. Pulmonary vascular remodeling was increased during aging, but aged p66Shc-/-mice showed similar muscularization of pulmonary vessels and hemodynamics like WT mice. In the heart, p66Shc-/-prevented the deterioration of right ventricular (RV) function but promoted the decline of left ventricular (LV) function during aging. p66Shc-/-affects the aging process of the lung and the heart differently. While p66Shc-/-slightly accelerates lung aging and deteriorates LV function in aged mice, it seems to exert protective effects on RV function during aging.
Zitierstile
Harvard-Zitierstil: Garcia Castro, C., Nardiello, C., Hadzic, S., Kojonazarov, B., Kraut, S., Gierhardt, M., et al. (2024) The Role of the Redox Enzyme p66Shc in Biological Aging of the Lung, Aging and Disease, 15(2), pp. 911-926. https://doi.org/10.14336/AD.2023.0715
APA-Zitierstil: Garcia Castro, C., Nardiello, C., Hadzic, S., Kojonazarov, B., Kraut, S., Gierhardt, M., Schäffer, J., Bednorz, M., Quanz, K., Heger, J., Korfei, M., Wilhelm, J., Hecker, M., Bartkuhn, M., Arnhold, S., Guenther, A., Seeger, W., Schulz, R., Weissmann, N., ...Pak, O. (2024). The Role of the Redox Enzyme p66Shc in Biological Aging of the Lung. Aging and Disease. 15(2), 911-926. https://doi.org/10.14336/AD.2023.0715
Schlagwörter
ADAPTER PROTEIN P66SHC; CELLULAR SENESCENCE; EMPHYSEMA; lung function; MN SUPEROXIDE-DISMUTASE; p66Shc; pulmonary vasculature; right ventricular function
