Analysis of representative mutants for key DNA repair pathways on healthspan in Caenorhabditis elegans
| Autor: | Roshan Karthikappallil, Himaly Shinglot, Lucile Marchal, Suhao Han, Shruthi Hamsanathan, Aditi U. Gurkar |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Aging
DNA Repair DNA damage DNA repair Mutant Longevity Biology medicine.disease_cause Genomic Instability Article medicine Animals Humans Caenorhabditis elegans Caenorhabditis elegans Proteins DNA Helicases Recombinational DNA Repair biology.organism_classification Cell biology Oxidative Stress Physiological Aging Mutation Homologous recombination Oxidative stress Developmental Biology Nucleotide excision repair DNA Damage |
| Zdroj: | Mech Ageing Dev |
| ISSN: | 1872-6216 |
| Popis: | Although the link between DNA damage and aging is well accepted, the role of different DNA repair proteins on functional/physiological aging is not well-defined. Here, using Caenorhabditis elegans, we systematically examined the effect of three DNA repair genes involved in key genomic stability pathways. We assayed multiple health proxies including molecular, functional and resilience measures to define healthspan. Mutation in XPF-1/ERCC-1, a protein involved in nucleotide excision repair (NER), homologous recombination (HR) and interstrand crosslink (ICL) repair, showed the highest impairment of functional and stress resilience measures along with a shortened lifespan. brc-1 mutants, with a well-defined role in HR and ICL are short-lived and highly sensitive to acute stressors, specifically oxidative stress. In contrast, ICL mutants fcd-2 did not impact lifespan or most healthspan measures. Our efforts also uncover that DNA repair mutants show high sensitivity to oxidative stress with age, suggesting that this measure could act as a primary proxy for healthspan. Together, these data suggest that impairment of multiple DNA repair genes can drive functional/physiological aging. Further studies to examine specific DNA repair genes in a tissue specific manner will help dissect the importance and mechanistic role of these repair systems in biological aging. |
| Databáze: | OpenAIRE |
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