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| Open AccessThe sperm of aging male bustards retards their offspring’s development
Sperm from aging males may decline in quality, but it is unclear how aging affects the ability of males to produce successful offspring. Here, the authors show that paternal aging of captive long-lived houbara bustards reduces both the likelihood that eggs hatch and the rate at which chicks grow.
- Brian T. Preston
- , Michel Saint Jalme
- & Gabriele Sorci
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| Open AccessFumarate induces redox-dependent senescence by modifying glutathione metabolism
Fumarate hydratase (FH) mutations are associated with renal cancer. Here, Zheng et al. use metabolomic and analytical chemistry approaches to reveal that fumarate accumulated due to FH loss covalently modifies intracellular glutathione, leading to oxidative stress and senescence.
- Liang Zheng
- , Simone Cardaci
- & Eyal Gottlieb
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| Open AccessA vlincRNA participates in senescence maintenance by relieving H2AZ-mediated repression at the INK4 locus
Senescence is associated with chromatin reorganization in heterochromatin foci. Here the authors show that VAD, a very long intergenic non-coding RNA activated by senescence, inhibits the incorporation of the repressive histone variant H2A.Z to INK4promoters in senescent cells.
- Sandra Lazorthes
- , Céline Vallot
- & Estelle Nicolas
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| Open AccessSpartan deficiency causes genomic instability and progeroid phenotypes
Spartan/DVC1 is a translesion synthesis regulator with important roles in cellular DNA damage tolerance. Here, the authors report that Spartan is essential for DNA lesion bypass and that Spartan insufficiency in mice causes chromosomal instability, cellular senescence and early onset of age-related phenotypes.
- Reeja S. Maskey
- , Myoung Shin Kim
- & Yuichi J. Machida
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| Open AccessLong noncoding RNA PANDA and scaffold-attachment-factor SAFA control senescence entry and exit
The gene-regulatory circuits that establish and maintain senescence remain incompletely understood. Here, the authors show that the long noncoding RNA PANDA and scaffold-attachment-factor A (SAFA) regulate entry and exit from senescence through context-specific interactions with PRC 1/2 and the transcription factor NF-YA.
- Pavan Kumar Puvvula
- , Rohini Devi Desetty
- & Oliver Bischof
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| Open AccessTRF2 and lamin A/C interact to facilitate the functional organization of chromosome ends
The shortening of telomeres—a structure that protects chromosome ends—is associated with cellular aging. Here, Wood et al.present evidence that interaction between the telomere-binding protein TRF2 and lamin A/C facilitates the formation of interstitial t-loops and stabilizes telomeres.
- Ashley M. Wood
- , Jannie M. Rendtlew Danielsen
- & Steven T. Kosak
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Histone H3.3 and its proteolytically processed form drive a cellular senescence programme
Cellular senescence involves extensive structural changes to chromatin, but the role of histone variants and histone cleavage is unknown. Here, Duarte et al.identify histone variant H3.3 and its proteolytically processed form lacking a portion of the N-terminal tail as key regulators of senescence.
- Luis F. Duarte
- , Andrew R. J. Young
- & Emily Bernstein
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Mitochondrial defects trigger proliferation of neighbouring cells via a senescence-associated secretory phenotype in Drosophila
Simultaneous mitochondrial dysfunction and Ras activation, which is commonly observed in cancer cells, has been shown to trigger the proliferation of neighbouring tissues in Drosophila. Nakamura et al.reveal that this effect is driven by a DNA-damage-induced senescence-associated secretory phenotype.
- Mai Nakamura
- , Shizue Ohsawa
- & Tatsushi Igaki
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Autophagic degradation of the inhibitory p53 isoform Δ133p53α as a regulatory mechanism for p53-mediated senescence
p53-mediated replicative senescence is associated with downregulation of the inhibitory p53 isoform Δ133p42α. Horikawa et al.show that this downregulation is a result of specific targeting of Δ133p42α for autophagic degradation by the E3 ubiquitin ligase STUB1.
- Izumi Horikawa
- , Kaori Fujita
- & Curtis C. Harris
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Phytochrome-interacting transcription factors PIF4 and PIF5 induce leaf senescence in Arabidopsis
In plants, light levels are sensed by phytochromes, and prolonged light deprivation triggers leaf senescence. Here, Sakuraba et al. show that the phytochrome-interacting transcription factors, PIF4 and PIF5, connect light sensing pathways with transcriptional networks that regulate leaf senescence in Arabidopsis.
- Yasuhito Sakuraba
- , Jinkil Jeong
- & Giltsu Choi
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| Open AccessChronic inflammation induces telomere dysfunction and accelerates ageing in mice
Many age-related diseases are associated with chronic inflammation. Here Jurk et al. use a mouse model of chronic, low-grade inflammation to support a model by which such inflammation promotes a vicious cycle of oxidative stress, telomere dysfunction and cell senescence that accelerates the ageing process.
- Diana Jurk
- , Caroline Wilson
- & Thomas von Zglinicki
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RETRACTED ARTICLE: Senescence impairs direct conversion of human somatic cells to neurons
Cellular senescence has been shown to inhibit reprogramming of fibroblasts to induced pluripotent stem cells. Here, the authors show that senescence pathways also impair the direct conversion of human fibroblasts into neurons.
- Chong-kui Sun
- , Di Zhou
- & Qin Yang
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Endoplasmic reticulum calcium release through ITPR2 channels leads to mitochondrial calcium accumulation and senescence
Cellular senescence is a protective mechanism that prevents replication of cells exposed to stresses such as replicative exhaustion, oncogenic signals and oxidative stress. Wiel et al.reveal a role for calcium signalling between the endoplasmic reticulum and mitochondria in senescence maintenance.
- Clotilde Wiel
- , Hélène Lallet-Daher
- & David Bernard
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| Open AccessThe Menin–Bach2 axis is critical for regulating CD4 T-cell senescence and cytokine homeostasis
Immunosenescence particularly affects the T-cell compartment and is involved in the age-related decline of immune functions. Here, the authors show that the absence of the tumour suppressor Menin results in premature senescence of CD4 T cells.
- Makoto Kuwahara
- , Junpei Suzuki
- & Masakatsu Yamashita
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ARF triggers senescence in Brca2-deficient cells by altering the spectrum of p53 transcriptional targets
The tumour suppressor ARF regulates p53 levels; however, in contrast to p53, ARF has not been implicated in the response to DNA damage. In this study, Carlos et al.show that single-stranded DNA formed in BRCA2-null cells triggers a DNA damage response leading to the activation of ARF and senescence.
- Ana Rita Carlos
- , Jose Miguel Escandell
- & Madalena Tarsounas
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Cdkn1b overexpression in adult mice alters the balance between genome and tissue ageing
Reduced rates of cell proliferation are thought to contribute to age-related tissue dysfunction. Here Pruitt et al.induce expression of the cell cycle inhibitor Cdkn1b in adult mice and show that this recapitulates ageing-related defects in tissue maintenance.
- Steven C. Pruitt
- , Amy Freeland
- & Gillian K. Cady
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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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p53 and p16INK4A independent induction of senescence by chromatin-dependent alteration of S-phase progression
Cellular senescence is characterized by the cessation of cell growth and the expression of the p16 protein. In this study, inhibition or loss of p300, a histone acetyltransferase, is shown to result in senescence that occurs independently of p16 and is associated with histone hypoacetylation and altered replication timing.
- Alexandre Prieur
- , Emilie Besnard
- & Jean-Marc Lemaitre