Volume 7, Issue 3

de Cabo R, Liu L, Ali A, Price N, Zhang J, Wang M, Lakatta E, Irusta PM, . Serum from calorie-restricted animals delays senescence and extends the lifespan of normal human fibroblasts in vitro. . 7:152-166. https://doi.org/10.18632/aging.100719

Copy or Download citation:

Select the format you require from the list below

Plain text
EndNote
Reference Manager
ProCite
BibteX

Provider: 
                TY  - JOUR
                AU  - de Cabo, Rafael 
                AU  - Liu, Lijuan 
                AU  - Ali, Ahmed 
                AU  - Price, Nathan 
                AU  - Zhang, Jing 
                AU  - Wang, Mingyi 
                AU  - Lakatta, Edward 
                AU  - Irusta, Pablo M. 
                TI  - Serum from calorie-restricted animals delays senescence and extends the lifespan of normal human fibroblasts <i>in vitro</i>
                JO  - 
                JA  - 
                VL  - 7
                IS  - 3
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100719
                DO  - 10.18632/aging.100719
                SP  - 152
                EP  - 166
                PY  - 
                AB  - 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.
                ER  -

Click to copy this citation from the text box above or download the citation:

Wound healing and longevity: Lessons from long-lived αMUPA mice

Hagai Yanai, Dimitri Toren, Klemens Vierlinger, Manuela Hofner, Christa Nöhammer, Marco Chilosi, Arie Budovsky, Vadim E. Fraifeld,

https://doi.org/10.18632/aging.100726 pp 167—176

View Abstract PDF Full-Text How to Cite Request Reprint

Cite this Article

How to cite

Yanai H, Toren D, Vierlinger K, Hofner M, Nöhammer C, Chilosi M, Budovsky A, Fraifeld VE, . Wound healing and longevity: Lessons from long-lived αMUPA mice. . 7:167-176. https://doi.org/10.18632/aging.100726

Copy or Download citation:

Select the format you require from the list below

Plain text
EndNote
Reference Manager
ProCite
BibteX

Provider: 
                TY  - JOUR
                AU  - Yanai, Hagai 
                AU  - Toren, Dimitri 
                AU  - Vierlinger, Klemens 
                AU  - Hofner, Manuela 
                AU  - Nöhammer, Christa 
                AU  - Chilosi, Marco 
                AU  - Budovsky, Arie 
                AU  - Fraifeld, Vadim E. 
                TI  - Wound healing and longevity: Lessons from long-lived αMUPA mice
                JO  - 
                JA  - 
                VL  - 7
                IS  - 3
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100726
                DO  - 10.18632/aging.100726
                SP  - 167
                EP  - 176
                PY  - 
                AB  - Does the longevity phenotype offer an advantage in wound healing (WH)? In an attempt to answer this question, we explored skin wound healing in the long-lived transgenic αMUPA mice, a unique model of genetically extended life span. These mice spontaneously eat less, preserve their body mass, are more resistant to spontaneous and induced tumorigenesis and live longer, thus greatly mimicking the effects of caloric restriction (CR). We found that αMUPA mice showed a much slower age-related decline in the rate of WH than their wild-type counterparts (FVB/N). After full closure of the wound, gene expression in the skin of old αMUPA mice returned close to basal levels. In contrast, old FVB/N mice still exhibited significant upregulation of genes associated with growth-promoting pathways, apoptosis and cell-cell/cell-extra cellular matrix interaction, indicating an ongoing tissue remodeling or an inability to properly shut down the repair process. It appears that the CR-like longevity phenotype is associated with more balanced and efficient WH mechanisms in old age, which could ensure a long-term survival advantage.
                ER  -

Click to copy this citation from the text box above or download the citation:

Functional genomic analysis reveals overlapping and distinct features of chronologically long-lived yeast populations

Margaret B. Wierman, Mirela Matecic, Veena Valsakumar, Mingguang Li, Daniel L. Smith Jr., Stefan Bekiranov, Jeffrey S. Smith,

https://doi.org/10.18632/aging.100729 pp 177—194

View Abstract PDF Full-Text How to Cite Request Reprint

Cite this Article

How to cite

Wierman MB, Matecic M, Valsakumar V, Li M, Smith DL, Bekiranov S, Smith JS, . Functional genomic analysis reveals overlapping and distinct features of chronologically long-lived yeast populations. . 7:177-194. https://doi.org/10.18632/aging.100729

Copy or Download citation:

Select the format you require from the list below

Plain text
EndNote
Reference Manager
ProCite
BibteX

Provider: 
                TY  - JOUR
                AU  - Wierman, Margaret B. 
                AU  - Matecic, Mirela 
                AU  - Valsakumar, Veena 
                AU  - Li, Mingguang 
                AU  - Smith, Daniel L. 
                AU  - Bekiranov, Stefan 
                AU  - Smith, Jeffrey S. 
                TI  - Functional genomic analysis reveals overlapping and distinct features of chronologically long-lived yeast populations
                JO  - 
                JA  - 
                VL  - 7
                IS  - 3
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100729
                DO  - 10.18632/aging.100729
                SP  - 177
                EP  - 194
                PY  - 
                AB  - Yeast chronological lifespan (CLS) is extended by multiple genetic and environmental manipulations, including caloric restriction (CR). Understanding the common changes in molecular pathways induced by such manipulations could potentially reveal conserved longevity mechanisms. We therefore performed gene expression profiling on several long-lived yeast populations, including an ade4∆ mutant defective in de novo purine (AMP) biosynthesis, and a calorie restricted WT strain. CLS was also extended by isonicotinamide (INAM) or expired media derived from CR cultures. Comparisons between these diverse long-lived conditions revealed a common set of differentially regulated genes, several of which were potential longevity biomarkers. There was also enrichment for genes that function in CLS regulation, including a long-lived adenosine kinase mutant (ado1∆) that links CLS regulation to the methyl cycle and AMP. Genes co-regulated between the CR and ade4∆ conditions were dominated by GO terms related to metabolism of alternative carbon sources, consistent with chronological longevity requiring efficient acetate/acetic acid utilization. Alternatively, treating cells with isonicotinamide (INAM) or the expired CR media resulted in GO terms predominantly related to cell wall remodeling, consistent with improved stress resistance and protection against external insults like acetic acid. Acetic acid therefore has both beneficial and detrimental effects on CLS.
                ER  -

Click to copy this citation from the text box above or download the citation:

Gene expression of key regulators of mitochondrial biogenesis is sex dependent in mice with growth hormone receptor deletion in liver

Ilona Zawada, Michal M. Masternak, Edward O. List, Michael B. Stout, Darlene E. Berryman, Andrzej Lewinski, John J. Kopchick, Andrzej Bartke, Malgorzata Karbownik-Lewinska, Adam Gesing,

https://doi.org/10.18632/aging.100733 pp 195—204

View Abstract PDF Full-Text How to Cite Request Reprint

Cite this Article

How to cite

Zawada I, Masternak MM, List EO, Stout MB, Berryman DE, Lewinski A, Kopchick JJ, Bartke A, Karbownik-Lewinska M, Gesing A, . Gene expression of key regulators of mitochondrial biogenesis is sex dependent in mice with growth hormone receptor deletion in liver. . 7:195-204. https://doi.org/10.18632/aging.100733

Copy or Download citation:

Select the format you require from the list below

Plain text
EndNote
Reference Manager
ProCite
BibteX

Provider: 
                TY  - JOUR
                AU  - Zawada, Ilona 
                AU  - Masternak, Michal M. 
                AU  - List, Edward O. 
                AU  - Stout, Michael B. 
                AU  - Berryman, Darlene E. 
                AU  - Lewinski, Andrzej 
                AU  - Kopchick, John J. 
                AU  - Bartke, Andrzej 
                AU  - Karbownik-Lewinska, Malgorzata 
                AU  - Gesing, Adam 
                TI  - Gene expression of key regulators of mitochondrial biogenesis is sex dependent in mice with growth hormone receptor deletion in liver
                JO  - 
                JA  - 
                VL  - 7
                IS  - 3
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100733
                DO  - 10.18632/aging.100733
                SP  - 195
                EP  - 204
                PY  - 
                AB  - Mitochondrial biogenesis is an essential process for cell viability. Mice with disruption of the growth hormone receptor (GHR) gene (Ghr gene) in the liver (LiGHRKO), in contrast to long-lived mice with global deletion of the Ghr gene (GHRKO), are characterized by lack of improved insulin sensitivity and severe hepatic steatosis. Tissue-specific disruption of the GHR in liver results in a mouse model with dramatically altered GH/IGF1 axis. We have previously shown increased levels of key regulators of mitochondrial biogenesis in insulin-sensitive GHRKO mice. The aim of the present study is to assess, using real-time PCR, the gene expression of key regulators of mitochondrial biogenesis (Pgc1α, Ampk, Sirt1, Nrf2 and Mfn2) and a marker of mitochondrial activity (CoxIV) in brains, kidneys and livers of male and female LiGHRKO and wild-type (WT) mice. There were significant differences between males and females. In the brain, expression of Pgc1α, Ampk, Sirt1, Nrf2 and Mfn2 was lower in pooled females compared to pooled males. In the kidneys, expression of Ampk and Sirt1 was also lower in female mice. In the liver, no differences between males and females were observed. Sexual dimorphism may play an important role in regulating the biogenesis of mitochondria.
                ER  -

Click to copy this citation from the text box above or download the citation:

The p53/miR-17/Smurf1 pathway mediates skeletal deformities in an age-related model via inhibiting the function of mesenchymal stem cells

Wenjia Liu, Meng Qi, Anna Konermann, Liqiang Zhang, Fang Jin, Yan Jin,

https://doi.org/10.18632/aging.100728 pp 205—218

View Abstract PDF Full-Text How to Cite Request Reprint

Cite this Article

How to cite

Liu W, Qi M, Konermann A, Zhang L, Jin F, Jin Y, . The p53/miR-17/Smurf1 pathway mediates skeletal deformities in an age-related model via inhibiting the function of mesenchymal stem cells. . 7:205-218. https://doi.org/10.18632/aging.100728

Copy or Download citation:

Select the format you require from the list below

Plain text
EndNote
Reference Manager
ProCite
BibteX

Provider: 
                TY  - JOUR
                AU  - Liu, Wenjia 
                AU  - Qi, Meng 
                AU  - Konermann, Anna 
                AU  - Zhang, Liqiang 
                AU  - Jin, Fang 
                AU  - Jin, Yan 
                TI  - The p53/miR-17/Smurf1 pathway mediates skeletal deformities in an age-related model via inhibiting the function of mesenchymal stem cells
                JO  - 
                JA  - 
                VL  - 7
                IS  - 3
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100728
                DO  - 10.18632/aging.100728
                SP  - 205
                EP  - 218
                PY  - 
                AB  - Osteoporosis is an age-related progressive bone disease. Trp53 (p53) is not only a famous senescence marker but also a transcription regulator which played a critical role in osteogenesis. However, how p53 contributes to the bone mass loss in age-related osteoporosis is still unclear. Here, we found that bone mass and osteogenic differentiation capacity of mesenchymal stem cells (MSCs) is significantly reduced with advancing age. Serum levels of TNF-α and INF-γ and senescence-associated ß-galactosidase, p16, p21 and p53 are significantly increased in elder mice, but antipodally, osteogenic marker expression of Runx2, ALP and osterix are reduced. Overexpression p53 by lentivirus inhibits osteogenesis in young MSCs in culture and upon implantation in NOD/SCID mice through inhibiting the transcription of miR-17-92 cluster, which is decreased in old mice. In addition, miR-17 mimics could partially rescue the osteogenesis of old MSCs both in vitro an in vivo. More importantly, Smurf1 as a direct target gene of miR-17, plays an important role in the p53/miR-17 cascade acting on osteogenesis. Our findings reveal that p53 inhibits osteogenesis via affecting the function of MSCs through miRNA signaling pathways and provide a new potential target for treatment in future.
                ER  -

Click to copy this citation from the text box above or download the citation:

Volume 7, Issue 3

Editorials

Synergy of cancer immunotherapy and radiotherapy

Aaron S. Mansfield, Sean S. Park, Haidong Dong,

microRNAs and oligometastasis

Nikolai N. Khodarev, Sean P. Pitroda, Ralph R. Weichselbaum,

Oncogenic drivers and mitochondrial dependency

Francesca Alvarez-Calderon, James DeGregori,

HGF-MET as a breast cancer biomarker

Shuying Liu,

Research Papers

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,

Wound healing and longevity: Lessons from long-lived αMUPA mice

Hagai Yanai, Dimitri Toren, Klemens Vierlinger, Manuela Hofner, Christa Nöhammer, Marco Chilosi, Arie Budovsky, Vadim E. Fraifeld,

Functional genomic analysis reveals overlapping and distinct features of chronologically long-lived yeast populations

Margaret B. Wierman, Mirela Matecic, Veena Valsakumar, Mingguang Li, Daniel L. Smith Jr., Stefan Bekiranov, Jeffrey S. Smith,

Gene expression of key regulators of mitochondrial biogenesis is sex dependent in mice with growth hormone receptor deletion in liver

Ilona Zawada, Michal M. Masternak, Edward O. List, Michael B. Stout, Darlene E. Berryman, Andrzej Lewinski, John J. Kopchick, Andrzej Bartke, Malgorzata Karbownik-Lewinska, Adam Gesing,

The p53/miR-17/Smurf1 pathway mediates skeletal deformities in an age-related model via inhibiting the function of mesenchymal stem cells

Wenjia Liu, Meng Qi, Anna Konermann, Liqiang Zhang, Fang Jin, Yan Jin,

Explore This Issue