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Research Paper|Volume 7, Issue 3|pp 152—166

Serum from calorie-restricted animals delays senescence and extends the lifespan of normal human fibroblasts in vitro

Rafael de Cabo1, Lijuan Liu1, Ahmed Ali1, Nathan Price1, Jing Zhang1, Mingyi Wang1, Edward Lakatta2, Pablo M. Irusta1,3
  • 1Experimental Gerontology Section, Translational Gerontology Branch, NIA/NIH, Baltimore, MD 21224, USA
  • 2Laboratory of Cardiovascular Science and Cardiovascular Function Section, NIA/NIH, Baltimore, MD 21224, USA
  • 3Department of Human Science, Georgetown University Medical Center, Washington, DC 20057 USA

* * Equal contribution

Received: August 12, 2014Accepted: January 11, 2015Published: January 13, 2015
https://doi.org/10.18632/aging.100719

Copyright: © 2015 de Cabo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The cumulative effects of cellular senescence and cell loss over time in various tissues and organs are considered major contributing factors to the ageing process. In various organisms, caloric restriction (CR) slows ageing and increases lifespan, at least in part, by activating nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases of the sirtuin family. Here, we use an in vitro model of CR to study the effects of this dietary regime on replicative senescence, cellular lifespan and modulation of the SIRT1 signaling pathway in normal human diploid fibroblasts. We found that serum from calorie-restricted animals was able to delay senescence and significantly increase replicative lifespan in these cells, when compared to serum from ad libitum fed animals. These effects correlated with CR-mediated increases in SIRT1 and decreases in p53 expression levels. In addition, we show that manipulation of SIRT1 levels by either over-expression or siRNA-mediated knockdown resulted in delayed and accelerated cellular senescence, respectively. Our results demonstrate that CR can delay senescence and increase replicative lifespan of normal human diploid fibroblasts in vitro and suggest that SIRT1 plays an important role in these processes.