<i>Atg4b</i> Overexpression Extends Lifespan and Healthspan in <i>Drosophila melanogaster</i>
Autophagy plays important but complex roles in aging, affecting health and longevity. We found that, in the general population, the levels of <i>ATG4B</i> and <i>ATG4D</i> decreased during aging, yet they are upregulated in centenarians, suggesting that overexpression of ATG4...
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MDPI AG
2023-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/12/9893 |
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| author | Yongxuan Li Wei Zhang Yunshuang Ye Yinan Sun Liping Yang Guijun Chen Kangning Chen Sheryl Smith Jumin Zhou |
| author_facet | Yongxuan Li Wei Zhang Yunshuang Ye Yinan Sun Liping Yang Guijun Chen Kangning Chen Sheryl Smith Jumin Zhou |
| author_sort | Yongxuan Li |
| collection | DOAJ |
| description | Autophagy plays important but complex roles in aging, affecting health and longevity. We found that, in the general population, the levels of <i>ATG4B</i> and <i>ATG4D</i> decreased during aging, yet they are upregulated in centenarians, suggesting that overexpression of ATG4 members could be positive for healthspan and lifespan. We therefore analyzed the effect of overexpressing <i>Atg4b</i> (a homolog of human <i>ATG4D</i>) in <i>Drosophila</i>, and found that, indeed, <i>Atg4b</i> overexpression increased resistance to oxidative stress, desiccation stress and fitness as measured by climbing ability. The overexpression induced since mid-life increased lifespan. Transcriptome analysis of <i>Drosophila</i> subjected to desiccation stress revealed that <i>Atg4b</i> overexpression increased stress response pathways. In addition, overexpression of <i>ATG4B</i> delayed cellular senescence, and improved cell proliferation. These results suggest that <i>ATG4B</i> have contributed to a slowdown in cellular senescence, and in <i>Drosophila</i>, <i>Atg4b</i> overexpression may have led to improved healthspan and lifespan by promoting a stronger stress response. Overall, our study suggests that <i>ATG4D</i> and <i>ATG4B</i> have the potential to become targets for health and lifespan interventions. |
| first_indexed | 2024-03-11T02:22:52Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T02:22:52Z |
| publishDate | 2023-06-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-cf2fb96988b34c0d909e53626ff20b012023-11-18T10:45:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-012412989310.3390/ijms24129893<i>Atg4b</i> Overexpression Extends Lifespan and Healthspan in <i>Drosophila melanogaster</i>Yongxuan Li0Wei Zhang1Yunshuang Ye2Yinan Sun3Liping Yang4Guijun Chen5Kangning Chen6Sheryl Smith7Jumin Zhou8Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, Kunming Institute of Zoology, Kunming 650223, ChinaKey Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, Kunming Institute of Zoology, Kunming 650223, ChinaKey Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, Kunming Institute of Zoology, Kunming 650223, ChinaKey Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, Kunming Institute of Zoology, Kunming 650223, ChinaKey Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, Kunming Institute of Zoology, Kunming 650223, ChinaKey Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, Kunming Institute of Zoology, Kunming 650223, ChinaKey Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, Kunming Institute of Zoology, Kunming 650223, ChinaBiology Department, Arcadia University, Philadelphia, PA 19104, USAKey Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, Kunming Institute of Zoology, Kunming 650223, ChinaAutophagy plays important but complex roles in aging, affecting health and longevity. We found that, in the general population, the levels of <i>ATG4B</i> and <i>ATG4D</i> decreased during aging, yet they are upregulated in centenarians, suggesting that overexpression of ATG4 members could be positive for healthspan and lifespan. We therefore analyzed the effect of overexpressing <i>Atg4b</i> (a homolog of human <i>ATG4D</i>) in <i>Drosophila</i>, and found that, indeed, <i>Atg4b</i> overexpression increased resistance to oxidative stress, desiccation stress and fitness as measured by climbing ability. The overexpression induced since mid-life increased lifespan. Transcriptome analysis of <i>Drosophila</i> subjected to desiccation stress revealed that <i>Atg4b</i> overexpression increased stress response pathways. In addition, overexpression of <i>ATG4B</i> delayed cellular senescence, and improved cell proliferation. These results suggest that <i>ATG4B</i> have contributed to a slowdown in cellular senescence, and in <i>Drosophila</i>, <i>Atg4b</i> overexpression may have led to improved healthspan and lifespan by promoting a stronger stress response. Overall, our study suggests that <i>ATG4D</i> and <i>ATG4B</i> have the potential to become targets for health and lifespan interventions.https://www.mdpi.com/1422-0067/24/12/9893<i>Atg4b</i>longevityhealthy aging<i>ATG4B</i>cellular senescence |
| spellingShingle | Yongxuan Li Wei Zhang Yunshuang Ye Yinan Sun Liping Yang Guijun Chen Kangning Chen Sheryl Smith Jumin Zhou <i>Atg4b</i> Overexpression Extends Lifespan and Healthspan in <i>Drosophila melanogaster</i> International Journal of Molecular Sciences <i>Atg4b</i> longevity healthy aging <i>ATG4B</i> cellular senescence |
| title | <i>Atg4b</i> Overexpression Extends Lifespan and Healthspan in <i>Drosophila melanogaster</i> |
| title_full | <i>Atg4b</i> Overexpression Extends Lifespan and Healthspan in <i>Drosophila melanogaster</i> |
| title_fullStr | <i>Atg4b</i> Overexpression Extends Lifespan and Healthspan in <i>Drosophila melanogaster</i> |
| title_full_unstemmed | <i>Atg4b</i> Overexpression Extends Lifespan and Healthspan in <i>Drosophila melanogaster</i> |
| title_short | <i>Atg4b</i> Overexpression Extends Lifespan and Healthspan in <i>Drosophila melanogaster</i> |
| title_sort | i atg4b i overexpression extends lifespan and healthspan in i drosophila melanogaster i |
| topic | <i>Atg4b</i> longevity healthy aging <i>ATG4B</i> cellular senescence |
| url | https://www.mdpi.com/1422-0067/24/12/9893 |
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