title: Serum from calorie-restricted animals delays senescence and extends the lifespan of normal human fibroblasts in vitro.
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.
authors: Experimental Gerontology Section, Translational Gerontology Branch, NIA/NIH, Baltimore, MD 21224, USA.
authors: Rafael
authors: R
authors: de Cabo
authors: Experimental Gerontology Section, Translational Gerontology Branch, NIA/NIH, Baltimore, MD 21224, USA.
authors: Lijuan
authors: L
authors: Liu
authors: Experimental Gerontology Section, Translational Gerontology Branch, NIA/NIH, Baltimore, MD 21224, USA.
authors: Ahmed
authors: A
authors: Ali
authors: Experimental Gerontology Section, Translational Gerontology Branch, NIA/NIH, Baltimore, MD 21224, USA.
authors: Nathan
authors: N
authors: Price
authors: Experimental Gerontology Section, Translational Gerontology Branch, NIA/NIH, Baltimore, MD 21224, USA.
authors: Jing
authors: J
authors: Zhang
authors: Experimental Gerontology Section, Translational Gerontology Branch, NIA/NIH, Baltimore, MD 21224, USA.
authors: Mingyi
authors: M
authors: Wang
authors: Laboratory of Cardiovascular Science and Cardiovascular Function Section, NIA/NIH, Baltimore, MD 21224, USA.
authors: Edward
authors: E
authors: Lakatta
authors: Experimental Gerontology Section, Translational Gerontology Branch, NIA/NIH, Baltimore, MD 21224, USA.|Department of Human Science, Georgetown University Medical Center, Washington, DC 20057 USA.
authors: Pablo M
authors: PM
authors: Irusta
mesh_terms: D000818:Animals; D031204:Caloric Restriction; D002460:Cell Line; D016922:Cellular Senescence; D017077:Culture Media, Conditioned; D004171:Diploidy; D015536:Down-Regulation; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D008136:Longevity; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D010641:Phenotype; D011916:Rats, Inbred F344; D044967:Serum; D056564:Sirtuin 1 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D016159:Tumor Suppressor Protein p53; C061901:GLB1 protein, human; D001616:beta-Galactosidase; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: SIRT1; aging; caloric restriction; human diploid fibroblasts; lifespan extension; senescence