The nuclear sirtuin SIRT6 protects the heart from developing aging-associated myocyte senescence and cardiac hypertrophy
| Autor: | Mahesh P. Gupta, Sadhana Samant, Samantha Hund, Madhu Gupta, Vinodkumar B. Pillai |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Senescence
SIRT6 Aging medicine.medical_specialty Cardiomegaly Protective Agents Mice Fibrosis Internal medicine medicine Animals Sirtuins Myocyte Myocytes Cardiac Doxorubicin Telomere Shortening biology Sirt6 business.industry Cell Biology medicine.disease Telomere Endocrinology Sirtuin biology.protein NAD+ kinase business cardiac aging DNA Damage Research Paper medicine.drug |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| DOI: | 10.18632/aging.203027 |
| Popis: | Sirtuins have been shown to regulate the aging process. We have previously demonstrated that Sirt6 blocks the pressure overload-induced cardiac hypertrophy in mice. Here, we show that Sirt6 can also mitigate aging-induced cardiomyocyte senescence and cardiac hypertrophy. We found that aging is associated with altered Sirt6 activity along with development of cardiac hypertrophy and fibrosis. Compared to young mice (4-months), the hearts of aged mice (24-months) showed increased levels of mitochondrial DNA damage, shortened telomere length, and increased accumulation of 8-oxo-dG adducts, which are hallmarks of aging. The aged hearts also showed reduced levels of NAD+ and altered levels of mitochondrial fusion-fission proteins. Similar characteristics were observed in the hearts of Sirt6 deficient mice. Additionally, we found that doxorubicin (Dox) induced cardiomyocyte senescence, as measured by expression of p16INK4a, p53, and β-galactosidase, was associated with loss of Sirt6. However, Sirt6 overexpression protected cardiomyocytes from developing Dox-induced senescence. Further, compared to wild-type mice, the hearts of Sirt6.Tg mice showed reduced expression of aging markers, and the development of aging-associated cardiac hypertrophy and fibrosis. Our data suggest that Sirt6 is a critical anti-aging molecule that regulates various cellular processes associated with aging and protects the heart from developing aging-induced cardiac hypertrophy and fibrosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|