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

Rafael de Cabo, Lijuan Liu, Ahmed Ali, Nathan Price, Jing Zhang, Mingyi Wang, Edward Lakatta, Pablo M. Irusta

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)152-166
Number of pages15
JournalAging
Volume7
Issue number3
DOIs
StatePublished - 2015
Externally publishedYes

Keywords

  • Aging
  • Caloric restriction
  • Human diploid fibroblasts
  • Lifespan extension
  • SIRT1
  • Senescence

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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