Aging and intermittent fasting impact on transcriptional regulation and physiological responses of adult drosophila neuronal and muscle tissues

Sharon Zhang, Eric P. Ratliff, Brandon Molina, Nadja El-Mecharrafie, Jessica Mastroianni, Roxanne W. Kotzebue, Madhulika Achal, Ruth E. Mauntz, Arysa Gonzalez, Ayeh Barekat, William A. Bray, Andrew M. Macias, Daniel Daugherty, Greg L. Harris, Robert A. Edwards, Kim D. Finley

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7 Citations (Scopus)

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.

Original languageEnglish
Article number1140
Number of pages20
JournalInternational Journal of Molecular Sciences
Volume19
Issue number4
DOIs
Publication statusPublished - Apr 2018
Externally publishedYes

Bibliographical note

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

Keywords

  • Aging
  • Aging-delaying interventions
  • Cellular proteostasis
  • Drosophila
  • Intermittent fasting
  • Metabolism
  • Neural degeneration
  • RNA-sequencing

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    Zhang, S., Ratliff, E. P., Molina, B., El-Mecharrafie, N., Mastroianni, J., Kotzebue, R. W., Achal, M., Mauntz, R. E., Gonzalez, A., Barekat, A., Bray, W. A., Macias, A. M., Daugherty, D., Harris, G. L., Edwards, R. A., & Finley, K. D. (2018). Aging and intermittent fasting impact on transcriptional regulation and physiological responses of adult drosophila neuronal and muscle tissues. International Journal of Molecular Sciences, 19(4), [1140]. https://doi.org/10.3390/ijms19041140