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Int J Mol Sci. 2018 Apr 10;19(4). pii: E1140. doi: 10.3390/ijms19041140.

Aging and Intermittent Fasting Impact on Transcriptional Regulation and Physiological Responses of Adult Drosophila Neuronal and Muscle Tissues.

Author information

1
Donald P. Shiley BioScience Center, San Diego State University, San Diego, CA 92182, USA. sharonzh10@yahoo.com.
2
Biological and Medical Informatics Research Center, San Diego State University, San Diego, CA 92182, USA. sharonzh10@yahoo.com.
3
Department of Biology, San Diego State University, San Diego, CA 92182, USA. sharonzh10@yahoo.com.
4
Donald P. Shiley BioScience Center, San Diego State University, San Diego, CA 92182, USA. epratliff@hotmail.com.
5
Department of Biology, San Diego State University, San Diego, CA 92182, USA. epratliff@hotmail.com.
6
Donald P. Shiley BioScience Center, San Diego State University, San Diego, CA 92182, USA. Brandonrm.16@gmail.com.
7
Department of Biology, San Diego State University, San Diego, CA 92182, USA. Brandonrm.16@gmail.com.
8
Donald P. Shiley BioScience Center, San Diego State University, San Diego, CA 92182, USA. nadjaelm@outlook.com.
9
Department of Biology, San Diego State University, San Diego, CA 92182, USA. nadjaelm@outlook.com.
10
Donald P. Shiley BioScience Center, San Diego State University, San Diego, CA 92182, USA. jmfmastroianni@yahoo.com.
11
Department of Biology, San Diego State University, San Diego, CA 92182, USA. jmfmastroianni@yahoo.com.
12
Donald P. Shiley BioScience Center, San Diego State University, San Diego, CA 92182, USA. rkotzebue@gmail.com.
13
Department of Biology, San Diego State University, San Diego, CA 92182, USA. rkotzebue@gmail.com.
14
Donald P. Shiley BioScience Center, San Diego State University, San Diego, CA 92182, USA. madhulika.achal@gmail.com.
15
Donald P. Shiley BioScience Center, San Diego State University, San Diego, CA 92182, USA. rmauntz@gmail.com.
16
Donald P. Shiley BioScience Center, San Diego State University, San Diego, CA 92182, USA. gonzalez.arysa@gmail.com.
17
Department of Biology, San Diego State University, San Diego, CA 92182, USA. gonzalez.arysa@gmail.com.
18
Donald P. Shiley BioScience Center, San Diego State University, San Diego, CA 92182, USA. ayeh.sdsu@gmail.com.
19
Department of Biology, San Diego State University, San Diego, CA 92182, USA. ayeh.sdsu@gmail.com.
20
Donald P. Shiley BioScience Center, San Diego State University, San Diego, CA 92182, USA. yossarianassyrian@gmail.com.
21
Department of Biology, San Diego State University, San Diego, CA 92182, USA. yossarianassyrian@gmail.com.
22
Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Dr., La Jolla, CA 92037, USA. yossarianassyrian@gmail.com.
23
Donald P. Shiley BioScience Center, San Diego State University, San Diego, CA 92182, USA. maciasandrew01@gmail.com.
24
Department of Biology, San Diego State University, San Diego, CA 92182, USA. maciasandrew01@gmail.com.
25
The Salk Institute for Biological Studies, Cellular Neurobiology, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. ddaugherty@salk.edu.
26
Department of Biology, San Diego State University, San Diego, CA 92182, USA. gharris@sdsu.edu.
27
Biological and Medical Informatics Research Center, San Diego State University, San Diego, CA 92182, USA. redwards@sdsu.edu.
28
Department of Biology, San Diego State University, San Diego, CA 92182, USA. redwards@sdsu.edu.
29
Donald P. Shiley BioScience Center, San Diego State University, San Diego, CA 92182, USA. kfinley@sdsu.edu.
30
Department of Biology, San Diego State University, San Diego, CA 92182, USA. kfinley@sdsu.edu.

Abstract

The progressive decline of the nervous system, including protein aggregate formation, reflects the subtle dysregulation of multiple functional pathways. Our previous work has shown intermittent fasting (IF) enhances longevity, maintains adult behaviors and reduces aggregates, in part, by promoting autophagic function in the aging Drosophila brain. To clarify the impact that IF-treatment has upon aging, we used high throughput RNA-sequencing technology to examine the changing transcriptome in adult Drosophila tissues. Principle component analysis (PCA) and other analyses showed ~1200 age-related transcriptional differences in head and muscle tissues, with few genes having matching expression patterns. Pathway components showing age-dependent expression differences were involved with stress response, metabolic, neural and chromatin remodeling functions. Middle-aged tissues also showed a significant increase in transcriptional drift-variance (TD), which in the CNS included multiple proteolytic pathway components. Overall, IF-treatment had a demonstrably positive impact on aged transcriptomes, partly ameliorating both fold and variance changes. Consistent with these findings, aged IF-treated flies displayed more youthful metabolic, behavioral and basal proteolytic profiles that closely correlated with transcriptional alterations to key components. These results indicate that even modest dietary changes can have therapeutic consequences, slowing the progressive decline of multiple cellular systems, including proteostasis in the aging nervous system.

KEYWORDS:

Drosophila; RNA-sequencing; aging; aging-delaying interventions; cellular proteostasis; intermittent fasting; metabolism; neural degeneration

PMID:
29642630
PMCID:
PMC5979431
DOI:
10.3390/ijms19041140
[Indexed for MEDLINE]
Free PMC Article

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