Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/214487
Title: STUDY OF EPIGENETIC REGULATORS AND SIGNATURES OF AGING
Authors: NGIAN ZHEN KAI
ORCID iD:   orcid.org/0000-0002-4134-2846
Keywords: Drosophila, Nelf-A, healthspan, heat-shock proteins, heterochromatin, stress responses
Issue Date: 16-Aug-2021
Citation: NGIAN ZHEN KAI (2021-08-16). STUDY OF EPIGENETIC REGULATORS AND SIGNATURES OF AGING. ScholarBank@NUS Repository.
Abstract: Epigenetic alteration is a hallmark of aging, but it remains unclear if perturbation of transcription machineries may affect longevity. NELF-mediated pausing of RNA polymerase II (RNAPII) constitutes an important step in transcription regulation. I found that halving NELF-A level in heterozygous mutants or via neuronal-specific depletion of NELF-A improves locomotor activity, stress resistance and lifespan of Drosophila significantly. Mechanistically, lower NELF-A releases paused RNAPII to facilitate productive transcription of the heat-shock protein (Hsp) genes. Elevated HSPs attenuate the level of protein aggregation, reactive oxidative species, DNA damage and systemic inflammation in the brains of NELF-A depleted flies. This protection is conserved in human cells where NELF-A depletion confers improved resistance against oxidative stress. Reduced oxidative DNA damage allows the maintenance of H3K9me2-enriched heterochromatin, which represses the activation of specific retrotransposons during aging. Therefore, by regulating transcription of Hsp genes in the brains, NELF-A controls multiple aspects of aging in Drosophila.
URI: https://scholarbank.nus.edu.sg/handle/10635/214487
Appears in Collections:Ph.D Theses (Open)

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