SIRT1 deacetylase in aging-induced neuromuscular degeneration and amyotrophic lateral sclerosis
Name
Herskovits_et_al-2018-Aging_Cell.pdf
Description
Published version
Size
1.69 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Herskovits, A. Zara
Hunter, Tegan A.
Maxwell, Nicholas
Pereira, Katherine
Whittaker, Charles A.
Valdez, Gregorio
Guarente, Leonard P.
Guarente, Leonard Pershing
Date Issued
October 2018
Journal
Aging Cell
Publisher
Wiley
Citation
Herskovits, Adrianna Z. et al. "SIRT1 deacetylase in aging-induced neuromuscular degeneration and amyotrophic lateral sclerosis." Aging Cell 17, 6 (October 2018): e12839 © 2018 The Authors
Version
Final published version
Abstract
Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. SIRT1 is an NAD+-dependent deacetylase that functions in a variety of cells and tissues to mitigate age-associated diseases. However, it remains unknown if SIRT1 also acts to prevent pathological changes that accrue in motor neurons during aging and amyotrophic lateral sclerosis (ALS). In this study, we show that SIRT1 expression decreases in the spinal cord of wild-type mice during normal aging. Using mouse models either overexpressing or lacking SIRT1 in motor neurons, we found that SIRT1 slows age-related degeneration of motor neurons’ presynaptic sites at neuromuscular junctions (NMJs). Transcriptional analysis of spinal cord shows an overlap of greater than 90% when comparing alterations during normal aging with changes during ALS, revealing a substantial upregulation in immune and inflammatory response genes and a downregulation of synaptic transcripts. In addition, overexpressing SIRT1 in motor neurons delays progression to end-stage disease in high copy SOD1G93A mice. Thus, our findings suggest that there are parallels between ALS and aging, and interventions to impede aging may also slow the progression of this devastating disease.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1111/acel.12839
