| Autor: |
Sakawdaurn Yasom, Papitchaya Watcharanurak, Narumol Bhummaphan, Jirapan Thongsroy, Charoenchai Puttipanyalears, Sirapat Settayanon, Kanwalat Chalertpet, Wilunplus Khumsri, Aphisek Kongkaew, Maturada Patchsung, Chutha Siriwattanakankul, Monnat Pongpanich, Piyapat Pin‐on, Depicha Jindatip, Rujira Wanotayan, Mingkwan Odton, Suangsuda Supasai, Thura Tun Oo, Busarin Arunsak, Wasana Pratchayasakul, Nipon Chattipakorn, Siriporn Chattipakorn, Apiwat Mutirangura |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
FASEB BioAdvances, Vol 4, Iss 6, Pp 408-434 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2573-9832 |
| DOI: |
10.1096/fba.2021-00131 |
| Popis: |
Abstract The endogenous DNA damage triggering an aging progression in the elderly is prevented in the youth, probably by naturally occurring DNA gaps. Decreased DNA gaps are found during chronological aging in yeast. So we named the gaps “Youth‐DNA‐GAPs.” The gaps are hidden by histone deacetylation to prevent DNA break response and were also reduced in cells lacking either the high‐mobility group box (HMGB) or the NAD‐dependent histone deacetylase, SIR2. A reduction in DNA gaps results in shearing DNA strands and decreasing cell viability. Here, we show the roles of DNA gaps in genomic stability and aging prevention in mammals. The number of Youth‐DNA‐GAPs were low in senescent cells, two aging rat models, and the elderly. Box A domain of HMGB1 acts as molecular scissors in producing DNA gaps. Increased gaps consolidated DNA durability, leading to DNA protection and improved aging features in senescent cells and two aging rat models similar to those of young organisms. Like the naturally occurring Youth‐DNA‐GAPs, Box A‐produced DNA gaps avoided DNA double‐strand break response by histone deacetylation and SIRT1, a Sir2 homolog. In conclusion, Youth‐DNA‐GAPs are a biomarker determining the DNA aging stage (young/old). Box A‐produced DNA gaps ultimately reverse aging features. Therefore, DNA gap formation is a potential strategy to monitor and treat aging‐associated diseases. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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