Title |
PGC-1α Modulates Telomere Function and DNA Damage in Protecting against Aging-Related Chronic Diseases
|
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Published in |
Cell Reports, August 2015
|
DOI | 10.1016/j.celrep.2015.07.047 |
Pubmed ID | |
Authors |
Shiqin Xiong, Nikolay Patrushev, Farshad Forouzandeh, Lula Hilenski, R. Wayne Alexander |
Abstract |
Cellular senescence and organismal aging predispose age-related chronic diseases, such as neurodegenerative, metabolic, and cardiovascular disorders. These diseases emerge coincidently from elevated oxidative/electrophilic stress, inflammation, mitochondrial dysfunction, DNA damage, and telomere dysfunction and shortening. Mechanistic linkages are incompletely understood. Here, we show that ablation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) accelerates vascular aging and atherosclerosis, coinciding with telomere dysfunction and shortening and DNA damage. PGC-1α deletion reduces expression and activity of telomerase reverse transcriptase (TERT) and increases p53 levels. Ectopic expression of PGC-1α coactivates TERT transcription and reverses telomere malfunction and DNA damage. Furthermore, alpha lipoic acid (ALA), a non-dispensable mitochondrial cofactor, upregulates PGC-1α-dependent TERT and the cytoprotective Nrf-2-mediated antioxidant/electrophile-responsive element (ARE/ERE) signaling cascades, and counteracts high-fat-diet-induced, age-dependent arteriopathy. These results illustrate the pivotal importance of PGC-1α in ameliorating senescence, aging, and associated chronic diseases, and may inform novel therapeutic approaches involving electrophilic specificity. |
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Norway | 4 | 16% |
Ireland | 1 | 4% |
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Japan | 1 | 4% |
Unknown | 13 | 52% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 21 | 84% |
Practitioners (doctors, other healthcare professionals) | 2 | 8% |
Science communicators (journalists, bloggers, editors) | 1 | 4% |
Scientists | 1 | 4% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United Kingdom | 2 | 2% |
Germany | 1 | 1% |
Unknown | 93 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 18 | 19% |
Student > Ph. D. Student | 16 | 17% |
Student > Master | 12 | 13% |
Student > Bachelor | 11 | 11% |
Other | 9 | 9% |
Other | 18 | 19% |
Unknown | 12 | 13% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 37 | 39% |
Medicine and Dentistry | 17 | 18% |
Agricultural and Biological Sciences | 16 | 17% |
Neuroscience | 3 | 3% |
Environmental Science | 1 | 1% |
Other | 7 | 7% |
Unknown | 15 | 16% |