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DNA damage accumulates with age (Lombard et al., 2005). However, whether and how robust DNA repair machinery promotes longevity is elusive. Here, we demonstrate that ATM-centered DNA damage response (DDR) progressively declines with senescence and age, while low dose of chloroquine (CQ) activates ATM, promotes DNA damage clearance, rescues age-related metabolic shift, and prolongs replicative lifespan. Molecularly, ATM phosphorylates SIRT6 deacetylase and thus prevents MDM2-mediated ubiquitination and proteasomal degradation. Extra copies of Sirt6 extend lifespan in Atm-/- mice, with restored metabolic homeostasis. Moreover, the treatment with CQ remarkably extends lifespan of Caenorhabditis elegans, but not the ATM-1 mutants. In a progeria mouse model with low DNA repair capacity, long-term administration of CQ ameliorates premature aging features and extends lifespan. Thus, our data highlights a pro-longevity role of ATM, for the first time establishing direct causal links between robust DNA repair machinery and longevity, and providing therapeutic strategy for progeria and age-related metabolic diseases.
Pubmed ID: 29717979 RIS Download
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A commercial antibody supplier and provider of various services.
View all literature mentionsGlobal nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.
View all literature mentionsNon-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsCommercial antibody vendor which supplies antibodies and other products to life science researchers.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis polyclonal targets Cleaved Caspase-3 (Asp175)
View all literature mentionsThis monoclonal targets detection of MDM2, MDM2 p60 cleavage product and p53-MDM2 complexes
View all literature mentionsThis monoclonal targets CDKN1A
View all literature mentionsThis monoclonal targets ATM, phospho (Ser1981)
View all literature mentionsThis monoclonal targets ATM
View all literature mentionsThis monoclonal targets Histone H2A.X, phospho (Ser139)
View all literature mentionsThis unknown targets LC3B
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets HA
View all literature mentionsThis monoclonal targets Phospho-ATM/ATR Substrate (S*Q) (D23H2/D69H5) Rabbit mAb
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Hep-G2 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis polyclonal targets Cleaved Caspase-3 (Asp175)
View all literature mentionsThis monoclonal targets ATM, phospho (Ser1981)
View all literature mentionsThis monoclonal targets detection of MDM2, MDM2 p60 cleavage product and p53-MDM2 complexes
View all literature mentionsThis monoclonal targets CDKN1A
View all literature mentionsThis monoclonal targets Histone H2A.X, phospho (Ser139)
View all literature mentionsThis monoclonal targets ATM
View all literature mentionsCell line Hep-G2 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis unknown targets LC3B
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets HA
View all literature mentionsThis polyclonal targets Cleaved Caspase-3 (Asp175)
View all literature mentionsThis monoclonal targets Phospho-ATM/ATR Substrate (S*Q) (D23H2/D69H5) Rabbit mAb
View all literature mentionsThis monoclonal targets ATM, phospho (Ser1981)
View all literature mentionsThis monoclonal targets detection of MDM2, MDM2 p60 cleavage product and p53-MDM2 complexes
View all literature mentionsThis monoclonal targets CDKN1A
View all literature mentionsThis monoclonal targets Histone H2A.X, phospho (Ser139)
View all literature mentionsThis monoclonal targets ATM
View all literature mentionsCell line U2OS is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Hep-G2 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets HA
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis unknown targets LC3B
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