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Involvement of Age-associated Golgi Stress in Impairment of Nuclear Translocation
- Author(s)
- ANA SOFIA PEREIRA DE BRITO
- Advisor
- Bum-Ho Bin
- Department
- 일반대학원 응용생명공학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2022-08
- Language
- eng
- Alternative Abstract
- In light of the increase in human life span, we are now faced with the task of not only increasing longevity but also boosting health span as we age. Cellular senescence is a key feature of aging that contributes to age-related illnesses and is also a viable therapeutic target. Furthermore, recent reports have demonstrated that senescence leads to inhibition of cytoplasm to nucleus nuclear translocation, but these mechanisms are yet far from being well understood. The Golgi apparatus is a stacked membrane organelle in the perinuclear region that functions as a center for protein and lipid trafficking as well as post-translational modifications of cargoes prior to delivery to their final destinations. However, it is not yet well understood how the Golgi apparatus changes during aging. Here, we found that the Golgi apparatus and Golgi-derived microtubules (Golgi MTs) are required for correct nuclear translocation of proteins for the regulation of cellular signaling and epigenetics. Furthermore, we reveal that age-related zinc deficiency elevates Golgi stress preventing the proper function of zinc-dependent stacking proteins on the Golgi-cisternal membrane. In addition, zinc deficiency also reduces Golgi-bound microtubule structures and induces defects on nuclear translocation of proteins in aged cells. Thus, we claim that zinc deficiency during aging produces a positive feedback loop with the disturbed Golgi apparatus, worsening fragmentation and exacerbating the aging phenotype. Our findings propose an explanation for why aged cells are less receptive to stimulation and highlight the importance of a proper zinc diet during aging.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Applied Biotechnology > 4. Theses(Ph.D)
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