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A Krüppel-like factor downstream of the E3 ligase WWP-1 mediates dietary-restriction-induced longevity in Caenorhabditis elegans
The ubiquitin ligase WWP-1 mediates the lifespan-increasing effect of dietary restriction (DR) in worms. Here the authors show that WWP-1 mono-ubiquitinylates the transcription factor Klf-1 in cultured cells and demonstrate that WWP-1 acts upstream of Klf-1 to regulate DR-induced longevity in worms.
- Andrea C. Carrano
- , Andrew Dillin
- & Tony Hunter
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| Open AccessD-Glucosamine supplementation extends life span of nematodes and of ageing mice
D-Glucosamine is a dietary supplement widely used for the treatment of osteoarthritis. Here Weimer et al. show that D-glucosamine extends the life span of Caenorhabditis elegans and of mice by mimicking the molecular effects of a diet low in carbohydrates.
- Sandra Weimer
- , Josephine Priebs
- & Michael Ristow
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Discriminating cellular heterogeneity using microwell-based RNA cytometry
Haematopoietic stem cell populations contain subgroups with distinct gene expression signatures and functional properties. Here, the authors present a method to uncover such subpopulations, based on flow cytometry to sort single cells into a microwell array followed by RNA expression measurements and statistical analyses.
- Ivan K. Dimov
- , Rong Lu
- & Luke P. Lee
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Model-based identification of drug targets that revert disrupted metabolism and its application to ageing
Systems biology is considered a promising tool for the identification of new drug targets. Here Yizhak and colleagues present an algorithm to analyse gene expression data and identify potential drug targets that would shift cellular metabolism from a given disease state to that of a healthier state.
- Keren Yizhak
- , Orshay Gabay
- & Eytan Ruppin
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| Open AccessPrelamin A causes progeria through cell-extrinsic mechanisms and prevents cancer invasion
Mutations in the metalloproteinase Zmpste24 preclude prelamin A processing and cause premature ageing. Here, de la Rosaet al.create mosaic Zmpste24 mice, revealing that cell-extrinsic effects are essential for accelerated ageing caused by prelamin A accumulation and that prelamin A reduces invasiveness of cancer cells.
- Jorge de la Rosa
- , José M.P. Freije
- & Carlos López-Otín
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| Open AccessExhaustion of nucleus pulposus progenitor cells with ageing and degeneration of the intervertebral disc
Back pain and sciatica are often caused by intervertebral disc degeneration. Sakai and colleagues identify a subset of nucleus pulposus progenitor cells from the intervertebral disc and show that loss of these progenitor cells correlates with ageing and intervertebral disc degeneration.
- Daisuke Sakai
- , Yoshihiko Nakamura
- & Joji Mochida
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| Open AccessTelomeres are favoured targets of a persistent DNA damage response in ageing and stress-induced senescence
Irreparable DNA damage leads to apoptosis or senescence. Hewittet al. show that, in response to genotoxic or oxidative stress, DNA damage occurs predominantly at telomere associated foci, which accumulate with age in vivo, irrespective of telomerase activity.
- Graeme Hewitt
- , Diana Jurk
- & João F. Passos
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| Open AccessMuscle-derived stem/progenitor cell dysfunction limits healthspan and lifespan in a murine progeria model
The function of adult stem cells is diminished with age but the role this dysfunction plays in the aging process is unknown. Here, the injection of muscle-derived stem/progenitor cells from young mice rescues symptoms in progeroid mice and is shown to regenerate tissues independent of engraftment.
- Mitra Lavasani
- , Andria R. Robinson
- & Johnny Huard
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| Open AccessRegenerative capacity in newts is not altered by repeated regeneration and ageing
Tissue regeneration is of great interest; however the number of times a given tissue can regenerate is unknown. Now, Eguchiet al. demonstrate that the lens of the Japanese newt—Cynops pyrrhogaster—can regenerate 18 times over a 16-year period, and that the new lenses are similar to those of control adult animals.
- Goro Eguchi
- , Yukiko Eguchi
- & Panagiotis A. Tsonis
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Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer
Ageing associated diseases are the subject of intense study. In this article Serrano and colleagues demonstrate that Sirt1 over-expression in mice prevents both ageing associated diseases and liver cancer.
- Daniel Herranz
- , Maribel Muñoz-Martin
- & Manuel Serrano