Aging-induced Akt activation involves in aging-related pathologies and Aβ-induced toxicity

Yu Ru Chen, Yu Hsuan Li, Tsung Chi Hsieh, Chih Ming Wang, Kuan Chung Cheng, Lei Wang, Tzu Yu Lin, Chun-Hei Cheung, Chia Lin Wu, HsuehCheng Chinag

Research output: Contribution to journalArticle

Abstract

Multicellular signals are altered in the processes of both aging and neurodegenerative diseases, including Alzheimer's disease (AD). Similarities in behavioral and cellular functional changes suggest a common regulator between aging and AD that remains undetermined. Our genetics and behavioral approaches revealed the regulatory role of Akt in both aging and AD pathogenesis. In this study, we found that the activity of Akt is upregulated during aging through epidermal growth factor receptor activation by using the fruit fly as an in vivo model. Downregulation of Akt in neurons improved cell survival, locomotor activity, and starvation challenge in both aged and Aβ42-expressing flies. Interestingly, increased cAMP levels attenuated both Akt activation-induced early death and Aβ42-induced learning deficit in flies. At the molecular level, overexpression of Akt promoted Notch cleavage, suggesting that Akt is an endogenous activity regulator of γ-secretase. Taken together, this study revealed that Akt is involved in the aging process and Aβ toxicity, and manipulating Akt can restore both neuronal functions and improve behavioral activity during the processes of aging and AD pathogenesis.

Original languageEnglish
Article numbere12989
JournalAging Cell
Volume18
Issue number4
DOIs
Publication statusPublished - 2019 Aug 1

Fingerprint

Alzheimer Disease
Pathology
Diptera
Behavioral Genetics
Amyloid Precursor Protein Secretases
Locomotion
Starvation
Epidermal Growth Factor Receptor
Neurodegenerative Diseases
Fruit
Cell Survival
Down-Regulation
Learning
Neurons

All Science Journal Classification (ASJC) codes

  • Ageing
  • Cell Biology

Cite this

Chen, Y. R., Li, Y. H., Hsieh, T. C., Wang, C. M., Cheng, K. C., Wang, L., ... Chinag, H. (2019). Aging-induced Akt activation involves in aging-related pathologies and Aβ-induced toxicity. Aging Cell, 18(4), [e12989]. https://doi.org/10.1111/acel.12989
Chen, Yu Ru ; Li, Yu Hsuan ; Hsieh, Tsung Chi ; Wang, Chih Ming ; Cheng, Kuan Chung ; Wang, Lei ; Lin, Tzu Yu ; Cheung, Chun-Hei ; Wu, Chia Lin ; Chinag, HsuehCheng. / Aging-induced Akt activation involves in aging-related pathologies and Aβ-induced toxicity. In: Aging Cell. 2019 ; Vol. 18, No. 4.
@article{b311a9ffcf774b5597a847946e568f82,
title = "Aging-induced Akt activation involves in aging-related pathologies and Aβ-induced toxicity",
abstract = "Multicellular signals are altered in the processes of both aging and neurodegenerative diseases, including Alzheimer's disease (AD). Similarities in behavioral and cellular functional changes suggest a common regulator between aging and AD that remains undetermined. Our genetics and behavioral approaches revealed the regulatory role of Akt in both aging and AD pathogenesis. In this study, we found that the activity of Akt is upregulated during aging through epidermal growth factor receptor activation by using the fruit fly as an in vivo model. Downregulation of Akt in neurons improved cell survival, locomotor activity, and starvation challenge in both aged and Aβ42-expressing flies. Interestingly, increased cAMP levels attenuated both Akt activation-induced early death and Aβ42-induced learning deficit in flies. At the molecular level, overexpression of Akt promoted Notch cleavage, suggesting that Akt is an endogenous activity regulator of γ-secretase. Taken together, this study revealed that Akt is involved in the aging process and Aβ toxicity, and manipulating Akt can restore both neuronal functions and improve behavioral activity during the processes of aging and AD pathogenesis.",
author = "Chen, {Yu Ru} and Li, {Yu Hsuan} and Hsieh, {Tsung Chi} and Wang, {Chih Ming} and Cheng, {Kuan Chung} and Lei Wang and Lin, {Tzu Yu} and Chun-Hei Cheung and Wu, {Chia Lin} and HsuehCheng Chinag",
year = "2019",
month = "8",
day = "1",
doi = "10.1111/acel.12989",
language = "English",
volume = "18",
journal = "Aging Cell",
issn = "1474-9718",
publisher = "Wiley-Blackwell",
number = "4",

}

Chen, YR, Li, YH, Hsieh, TC, Wang, CM, Cheng, KC, Wang, L, Lin, TY, Cheung, C-H, Wu, CL & Chinag, H 2019, 'Aging-induced Akt activation involves in aging-related pathologies and Aβ-induced toxicity', Aging Cell, vol. 18, no. 4, e12989. https://doi.org/10.1111/acel.12989

Aging-induced Akt activation involves in aging-related pathologies and Aβ-induced toxicity. / Chen, Yu Ru; Li, Yu Hsuan; Hsieh, Tsung Chi; Wang, Chih Ming; Cheng, Kuan Chung; Wang, Lei; Lin, Tzu Yu; Cheung, Chun-Hei; Wu, Chia Lin; Chinag, HsuehCheng.

In: Aging Cell, Vol. 18, No. 4, e12989, 01.08.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Aging-induced Akt activation involves in aging-related pathologies and Aβ-induced toxicity

AU - Chen, Yu Ru

AU - Li, Yu Hsuan

AU - Hsieh, Tsung Chi

AU - Wang, Chih Ming

AU - Cheng, Kuan Chung

AU - Wang, Lei

AU - Lin, Tzu Yu

AU - Cheung, Chun-Hei

AU - Wu, Chia Lin

AU - Chinag, HsuehCheng

PY - 2019/8/1

Y1 - 2019/8/1

N2 - Multicellular signals are altered in the processes of both aging and neurodegenerative diseases, including Alzheimer's disease (AD). Similarities in behavioral and cellular functional changes suggest a common regulator between aging and AD that remains undetermined. Our genetics and behavioral approaches revealed the regulatory role of Akt in both aging and AD pathogenesis. In this study, we found that the activity of Akt is upregulated during aging through epidermal growth factor receptor activation by using the fruit fly as an in vivo model. Downregulation of Akt in neurons improved cell survival, locomotor activity, and starvation challenge in both aged and Aβ42-expressing flies. Interestingly, increased cAMP levels attenuated both Akt activation-induced early death and Aβ42-induced learning deficit in flies. At the molecular level, overexpression of Akt promoted Notch cleavage, suggesting that Akt is an endogenous activity regulator of γ-secretase. Taken together, this study revealed that Akt is involved in the aging process and Aβ toxicity, and manipulating Akt can restore both neuronal functions and improve behavioral activity during the processes of aging and AD pathogenesis.

AB - Multicellular signals are altered in the processes of both aging and neurodegenerative diseases, including Alzheimer's disease (AD). Similarities in behavioral and cellular functional changes suggest a common regulator between aging and AD that remains undetermined. Our genetics and behavioral approaches revealed the regulatory role of Akt in both aging and AD pathogenesis. In this study, we found that the activity of Akt is upregulated during aging through epidermal growth factor receptor activation by using the fruit fly as an in vivo model. Downregulation of Akt in neurons improved cell survival, locomotor activity, and starvation challenge in both aged and Aβ42-expressing flies. Interestingly, increased cAMP levels attenuated both Akt activation-induced early death and Aβ42-induced learning deficit in flies. At the molecular level, overexpression of Akt promoted Notch cleavage, suggesting that Akt is an endogenous activity regulator of γ-secretase. Taken together, this study revealed that Akt is involved in the aging process and Aβ toxicity, and manipulating Akt can restore both neuronal functions and improve behavioral activity during the processes of aging and AD pathogenesis.

UR - http://www.scopus.com/inward/record.url?scp=85068797504&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85068797504&partnerID=8YFLogxK

U2 - 10.1111/acel.12989

DO - 10.1111/acel.12989

M3 - Article

VL - 18

JO - Aging Cell

JF - Aging Cell

SN - 1474-9718

IS - 4

M1 - e12989

ER -