Functional restoration of lysosomes and mitochondria through modulation of AKT activity ameliorates senescence
Senescence is a phenomenon defined by alterations in cellular organelles and is the primary cause of aging and aging-related diseases. Recent studies have shown that oncogene-induced senescence is driven by activation of serine/threonine protein kinases (AKT1, AKT2 and AKT3). In this study, we evalu...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-03-01
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| Series: | Experimental Gerontology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0531556523000128 |
| _version_ | 1797776168449998848 |
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| author | Myeong Uk Kuk Haneur Lee Eun Seon Song Yun Haeng Lee Ji Yun Park Subin Jeong Hyung Wook Kwon Youngjoo Byun Sang Chul Park Joon Tae Park |
| author_facet | Myeong Uk Kuk Haneur Lee Eun Seon Song Yun Haeng Lee Ji Yun Park Subin Jeong Hyung Wook Kwon Youngjoo Byun Sang Chul Park Joon Tae Park |
| author_sort | Myeong Uk Kuk |
| collection | DOAJ |
| description | Senescence is a phenomenon defined by alterations in cellular organelles and is the primary cause of aging and aging-related diseases. Recent studies have shown that oncogene-induced senescence is driven by activation of serine/threonine protein kinases (AKT1, AKT2 and AKT3). In this study, we evaluated twelve AKT inhibitors and revealed GDC0068 as a potential agent to ameliorate senescence. Senescence-ameliorating effect was evident from the finding that GDC0068 yielded lysosomal functional recovery as observed by reduction in lysosomal mass and induction in autophagic flux. Furthermore, GDC0068-mediated restoration of lysosomal function activated the removal of dysfunctional mitochondria, resulting in restoration of mitochondrial function. Together, our findings revealed a unique mechanism by which senescence is recovered by functional restoration of lysosomes and mitochondria through modulation of AKT activity. |
| first_indexed | 2024-03-12T22:47:08Z |
| format | Article |
| id | doaj.art-5c5b0656dcf3499ca10a8137cddfb115 |
| institution | Directory Open Access Journal |
| issn | 1873-6815 |
| language | English |
| last_indexed | 2024-03-12T22:47:08Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Experimental Gerontology |
| spelling | doaj.art-5c5b0656dcf3499ca10a8137cddfb1152023-07-21T04:58:50ZengElsevierExperimental Gerontology1873-68152023-03-01173112091Functional restoration of lysosomes and mitochondria through modulation of AKT activity ameliorates senescenceMyeong Uk Kuk0Haneur Lee1Eun Seon Song2Yun Haeng Lee3Ji Yun Park4Subin Jeong5Hyung Wook Kwon6Youngjoo Byun7Sang Chul Park8Joon Tae Park9Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Republic of KoreaDivision of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Republic of KoreaDivision of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Republic of KoreaDivision of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Republic of KoreaDivision of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Republic of KoreaDivision of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Republic of KoreaDivision of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Republic of Korea; Convergence Research Center for Insect Vectors, Incheon National University, Incheon 22012, Republic of KoreaCollege of Pharmacy, Korea University, Sejong 30019, Republic of Korea; Corresponding authors.The Future Life & Society Research Center, Chonnam National University, Gwangju, Republic of Korea; Corresponding authors.Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Republic of Korea; Convergence Research Center for Insect Vectors, Incheon National University, Incheon 22012, Republic of Korea; Correspondence to: J.T. Park, Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Republic of Korea.Senescence is a phenomenon defined by alterations in cellular organelles and is the primary cause of aging and aging-related diseases. Recent studies have shown that oncogene-induced senescence is driven by activation of serine/threonine protein kinases (AKT1, AKT2 and AKT3). In this study, we evaluated twelve AKT inhibitors and revealed GDC0068 as a potential agent to ameliorate senescence. Senescence-ameliorating effect was evident from the finding that GDC0068 yielded lysosomal functional recovery as observed by reduction in lysosomal mass and induction in autophagic flux. Furthermore, GDC0068-mediated restoration of lysosomal function activated the removal of dysfunctional mitochondria, resulting in restoration of mitochondrial function. Together, our findings revealed a unique mechanism by which senescence is recovered by functional restoration of lysosomes and mitochondria through modulation of AKT activity.http://www.sciencedirect.com/science/article/pii/S0531556523000128AKTGDC0068Senescence ameliorationLysosomeMitochondria |
| spellingShingle | Myeong Uk Kuk Haneur Lee Eun Seon Song Yun Haeng Lee Ji Yun Park Subin Jeong Hyung Wook Kwon Youngjoo Byun Sang Chul Park Joon Tae Park Functional restoration of lysosomes and mitochondria through modulation of AKT activity ameliorates senescence Experimental Gerontology AKT GDC0068 Senescence amelioration Lysosome Mitochondria |
| title | Functional restoration of lysosomes and mitochondria through modulation of AKT activity ameliorates senescence |
| title_full | Functional restoration of lysosomes and mitochondria through modulation of AKT activity ameliorates senescence |
| title_fullStr | Functional restoration of lysosomes and mitochondria through modulation of AKT activity ameliorates senescence |
| title_full_unstemmed | Functional restoration of lysosomes and mitochondria through modulation of AKT activity ameliorates senescence |
| title_short | Functional restoration of lysosomes and mitochondria through modulation of AKT activity ameliorates senescence |
| title_sort | functional restoration of lysosomes and mitochondria through modulation of akt activity ameliorates senescence |
| topic | AKT GDC0068 Senescence amelioration Lysosome Mitochondria |
| url | http://www.sciencedirect.com/science/article/pii/S0531556523000128 |
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