A conserved KLF-autophagy pathway modulates nematode lifespan and mammalian age-associated vascular dysfunction

Abstract

Loss of protein and organelle quality control secondary to reduced autophagy is a hallmark of aging. However, the physiologic and molecular regulation of autophagy in long-lived organisms remains incompletely understood. Here we show that the Kruppel-like family of transcription factors are important regulators of autophagy and healthspan in C. elegans, and also modulate mammalian vascular age-associated phenotypes. Kruppel-like family of transcription factor deficiency attenuates autophagy and lifespan extension across mechanistically distinct longevity nematode models. Conversely, Kruppel-like family of transcription factor overexpression extends nematode lifespan in an autophagy-dependent manner. Furthermore, we show the mammalian vascular factor Kruppel-like family of transcription factor 4 has a conserved role in augmenting autophagy and improving vessel function in aged mice. Kruppel-like family of transcription factor 4 expression also decreases with age in human vascular endothelium. Thus, Kruppel-like family of transcription factors constitute a transcriptional regulatory point for the modulation of autophagy and longevity in C. elegans with conserved effects in the murine vasculature and potential implications for mammalian vascular aging.

Publisher

Nature Publishing Group

Publication Date

10-13-2017

Publication Title

Nature Communications

Department

Biology

Document Type

Article

DOI

https://dx.doi.org/10.1038/s41467-017-00899-5

Keywords

Ageing, Arterial stiffening, Caenorhabditis elegans, Macroautophagy

Language

English

Format

text

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