Genomes and Genes
Summary: Process by which cells irreversibly stop dividing and enter a state of permanent growth arrest without undergoing CELL DEATH. Senescence can be induced by DNA DAMAGE or other cellular stresses, such as OXIDATIVE STRESS.
- Kim Y, Byun H, Jee B, Cho H, Seo Y, Kim Y, et al. Implications of time-series gene expression profiles of replicative senescence. Aging Cell. 2013;12:622-34 pubmed publisher..Taken together, our results reflect a detailed process of cellular senescence and provide diverse genome-wide information of cellular backgrounds for senescence. ..
- Greussing R, Hackl M, Charoentong P, Pauck A, Monteforte R, Cavinato M, et al. Identification of microRNA-mRNA functional interactions in UVB-induced senescence of human diploid fibroblasts. BMC Genomics. 2013;14:224 pubmed publisher..In addition, miR-101 and Ezh2 were identified as key players in UVB-induced senescence of HDF. ..
- Beerman I, Bock C, Garrison B, Smith Z, Gu H, Meissner A, et al. Proliferation-dependent alterations of the DNA methylation landscape underlie hematopoietic stem cell aging. Cell Stem Cell. 2013;12:413-25 pubmed publisher..Our results provide evidence that epigenomic alterations of the DNA methylation landscape contribute to the functional decline of HSCs during aging. ..
- Hubackova S, Krejcikova K, Bartek J, Hodny Z. IL1- and TGF?-Nox4 signaling, oxidative stress and DNA damage response are shared features of replicative, oncogene-induced, and drug-induced paracrine 'bystander senescence'. Aging (Albany NY). 2012;4:932-51 pubmed
- Sagiv A, Krizhanovsky V. Immunosurveillance of senescent cells: the bright side of the senescence program. Biogerontology. 2013;14:617-28 pubmed publisher..Here, we summarize the current advances in our knowledge of the mechanisms underlying specific immune-mediated elimination of senescent cells. ..
- Yu K, Lee S, Jung J, Hong I, Kim H, Seo Y, et al. MicroRNA-141-3p plays a role in human mesenchymal stem cell aging by directly targeting ZMPSTE24. J Cell Sci. 2013;126:5422-31 pubmed publisher..This study provides new insights into mechanisms regulating MSC aging and may have implications for therapeutic application to reduce age-associated MSC pool exhaustion. ..
- Van Zant G, Liang Y. Concise review: hematopoietic stem cell aging, life span, and transplantation. Stem Cells Transl Med. 2012;1:651-7 pubmed publisher..Genetic variants and factors regulating stem cell aging are correlatively or causatively associated with overall organismal aging and longevity...
- Wahlestedt M, Norddahl G, Sten G, Ugale A, Frisk M, Mattsson R, et al. An epigenetic component of hematopoietic stem cell aging amenable to reprogramming into a young state. Blood. 2013;121:4257-64 pubmed publisher..Our results, therefore, favor a model in which an underlying, but reversible, epigenetic component is a hallmark of HSC aging. ..
- Signer R, Morrison S. Mechanisms that regulate stem cell aging and life span. Cell Stem Cell. 2013;12:152-65 pubmed publisher..It remains unknown whether declines in stem cell function during aging influence organismal longevity. However, mechanisms that influence longevity also modulate age-related morbidity, partly through effects on stem cells. ..
- Cruickshanks H, McBryan T, Nelson D, Vanderkraats N, Shah P, van Tuyn J, et al. Senescent cells harbour features of the cancer epigenome. Nat Cell Biol. 2013;15:1495-506 pubmed publisher..Consequently, the DNA methylome of senescent cells might promote malignancy, if these cells escape the proliferative barrier. ..
- Miller J, Ganat Y, Kishinevsky S, Bowman R, Liu B, Tu E, et al. Human iPSC-based modeling of late-onset disease via progerin-induced aging. Cell Stem Cell. 2013;13:691-705 pubmed publisher..Thus, our study suggests that progerin-induced aging can be used to reveal late-onset age-related disease features in hiPSC-based disease models. ..
- Davalos A, Kawahara M, Malhotra G, Schaum N, Huang J, Ved U, et al. p53-dependent release of Alarmin HMGB1 is a central mediator of senescent phenotypes. J Cell Biol. 2013;201:613-29 pubmed publisher..Our findings identify senescence as a novel biological setting in which HMGB1 functions and link HMGB1 redistribution to p53 activity and senescence-associated inflammation. ..
- Luo H, Yang A, Schulte B, Wargovich M, Wang G. Resveratrol induces premature senescence in lung cancer cells via ROS-mediated DNA damage. PLoS ONE. 2013;8:e60065 pubmed publisher..Together, these findings demonstrate that low dose RV treatment inhibits lung cancer cell growth via a previously unappreciated mechanism, namely the induction of premature senescence through ROS-mediated DNA damage. ..
- Mallette F, Richard S. JMJD2A promotes cellular transformation by blocking cellular senescence through transcriptional repression of the tumor suppressor CHD5. Cell Rep. 2012;2:1233-43 pubmed publisher..Depletion of JMJD2A in the human lung cancer cell line A549 bearing an activated K-Ras allele triggers senescence. We propose that JMJD2A is an oncogene that represents a target for Ras-expressing tumors. ..
- Halicka H, Zhao H, Li J, Lee Y, Hsieh T, Wu J, et al. Potential anti-aging agents suppress the level of constitutive mTOR- and DNA damage- signaling. Aging (Albany NY). 2012;4:952-65 pubmed..rate of translation induced by these agents may slow down cells hypertrophy and alleviate other features of cell aging/senescence...
- Blagosklonny M. Answering the ultimate question "what is the proximal cause of aging?". Aging (Albany NY). 2012;4:861-77 pubmed..I discuss that these arguments actually support a new theory. Are any questions remaining? And might accumulation of molecular damage still play a peculiar role in aging? ..
- Cahu J, Bustany S, Sola B. Senescence-associated secretory phenotype favors the emergence of cancer stem-like cells. Cell Death Dis. 2012;3:e446 pubmed publisher..This mechanism, based on mutual cooperation among tumor cells, illustrates how cancer may relapse; its targeting could represent new therapeutic opportunities. ..
- Seol M, Jung U, Eom H, Kim S, Park H, Jo S. Prolonged expression of senescence markers in mice exposed to gamma-irradiation. J Vet Sci. 2012;13:331-8 pubmed..This should be considered when dealing with chronic normal tissue injuries caused by radiation therapy or radiation accidents. ..
- Yentrapalli R, Azimzadeh O, Sriharshan A, Malinowsky K, Merl J, Wojcik A, et al. The PI3K/Akt/mTOR pathway is implicated in the premature senescence of primary human endothelial cells exposed to chronic radiation. PLoS ONE. 2013;8:e70024 pubmed publisher..We postulate that a similar endothelial aging may contribute to the increased rate of CVD seen in populations chronically exposed to low-dose-rate radiation. ..
- Ivanov A, Pawlikowski J, Manoharan I, van Tuyn J, Nelson D, Rai T, et al. Lysosome-mediated processing of chromatin in senescence. J Cell Biol. 2013;202:129-43 pubmed publisher..We conclude that senescent cells process their chromatin via an autophagy/lysosomal pathway and that this might contribute to stability of senescence and tumor suppression. ..
- ..This review, far from being exhaustive given the complexity of the field, will hopefully stimulate further research in this domain, whose relevance for ageing is becoming increasingly documented. ..
- Luo H, Yount C, Lang H, Yang A, Riemer E, Lyons K, et al. Activation of p53 with Nutlin-3a radiosensitizes lung cancer cells via enhancing radiation-induced premature senescence. Lung Cancer. 2013;81:167-73 pubmed publisher..Taken together, these findings demonstrate for the first time that pharmacological activation of p53 by Nutlin-3a can sensitize lung cancer cells to radiation therapy via promoting IR-induced premature senescence. ..
- Benetos A, Kark J, Susser E, Kimura M, Sinnreich R, Chen W, et al. Tracking and fixed ranking of leukocyte telomere length across the adult life course. Aging Cell. 2013;12:615-21 pubmed publisher..Accordingly, the links of LTL with atherosclerosis and longevity appear to be established early in life. It is unlikely that lifestyle and its modification during adulthood exert a major impact on LTL ranking...
- Ye C, Zhang X, Wan J, Chang L, Hu W, Bing Z, et al. Radiation-induced cellular senescence results from a slippage of long-term G2 arrested cells into G1 phase. Cell Cycle. 2013;12:1424-32 pubmed publisher..To our knowledge, this is the first study to report that the cellular process of G2 slippage is the mechanism responsible for senescence of cells under long-term G2 arrest. ..
- Cao L, Wang H, Wang F, Xu D, Liu F, Liu C. A?-induced senescent retinal pigment epithelial cells create a proinflammatory microenvironment in AMD. Invest Ophthalmol Vis Sci. 2013;54:3738-50 pubmed publisher..Silence of MMP-9 preserved the barrier integrity of senescent RPE cells. The altered secretory phenotype of senescent RPE cells may contribute to age-related inflammation in AMD. Chinese Abstract. ..
- Zhou J, Freeman T, Ahmad F, Shang X, Mangano E, Gao E, et al. GSK-3? is a central regulator of age-related pathologies in mice. J Clin Invest. 2013;123:1821-32 pubmed publisher..In its absence, aging/senescence is accelerated in multiple tissues. Strategies to maintain GSK-3? activity and/or inhibit mTOR in the elderly could retard the appearance of age-related pathologies. ..
- Blagosklonny M. Rapalogs in cancer prevention: anti-aging or anticancer?. Cancer Biol Ther. 2012;13:1349-54 pubmed publisher..Can cancer prevention be explained by direct targeting of cancer cells? Or does rapamycin prevent cancer indirectly through slowing down the aging process? Increasing evidence points to the latter scenario. ..
- Wang Y, Chen T, Yan H, Qi H, Deng C, Ye T, et al. Role of histone deacetylase inhibitors in the aging of human umbilical cord mesenchymal stem cells. J Cell Biochem. 2013;114:2231-9 pubmed publisher..HDACis can affect histone H3 lysine 9 or 14 acetylation and histone H3 lysine 4 dimethylation, thus increasing the mRNA expression of pluripotent and proliferative genes and suppressing the spontaneous differentiation of hUC-MSCs...
- Dreesen O, Chojnowski A, Ong P, Zhao T, Common J, Lunny D, et al. Lamin B1 fluctuations have differential effects on cellular proliferation and senescence. J Cell Biol. 2013;200:605-17 pubmed publisher..This phenotype was exacerbated by a simultaneous reduction of LMNA/C. Our results demonstrate that altering LMNB1 levels inhibits proliferation and are relevant to understanding the molecular pathology of ADLD. ..
- Hildebrand D, Lehle S, Borst A, Haferkamp S, Essmann F, Schulze Osthoff K. ?-Fucosidase as a novel convenient biomarker for cellular senescence. Cell Cycle. 2013;12:1922-7 pubmed publisher..As ?-Fuc is convenient and easy to measure, we suggest its utility as a valuable marker, in particular in cells with low SA-?-Gal activity. ..
- Alessio N, Bohn W, Rauchberger V, Rizzolio F, Cipollaro M, Rosemann M, et al. Silencing of RB1 but not of RB2/P130 induces cellular senescence and impairs the differentiation potential of human mesenchymal stem cells. Cell Mol Life Sci. 2013;70:1637-51 pubmed publisher..In summary, our data show evidence that the silencing of the expression of RB1 or RB2/P130 is not compensated by other gene family members, and this profoundly affects MSC functions. ..
- Acosta J, Banito A, Wuestefeld T, Georgilis A, Janich P, Morton J, et al. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol. 2013;15:978-90 pubmed publisher..Our results demonstrate that the SASP can cause paracrine senescence and impact on tumour suppression and senescence in vivo. ..
- Moiseeva O, Deschênes Simard X, St Germain E, Igelmann S, Huot G, Cadar A, et al. Metformin inhibits the senescence-associated secretory phenotype by interfering with IKK/NF-?B activation. Aging Cell. 2013;12:489-98 pubmed publisher..Taken together, our results provide a novel mechanism for the antiaging and antineoplastic effects of metformin reported in animal models and in diabetic patients taking this drug. ..
- Panganiban R, Snow A, Day R. Mechanisms of radiation toxicity in transformed and non-transformed cells. Int J Mol Sci. 2013;14:15931-58 pubmed publisher..Understanding the molecular mechanisms of radiation toxicity is critical for the development of radiation countermeasures as well as for the improvement of clinical radiation in cancer treatment. ..
- De Cecco M, Criscione S, Peckham E, Hillenmeyer S, Hamm E, Manivannan J, et al. Genomes of replicatively senescent cells undergo global epigenetic changes leading to gene silencing and activation of transposable elements. Aging Cell. 2013;12:247-56 pubmed publisher..These epigenetic changes progress slowly after the onset of senescence, with some, such as mobilization of retrotransposable elements becoming prominent only at late times. Many of these changes have also been noted in cancer cells. ..
- Leontieva O, Lenzo F, Demidenko Z, Blagosklonny M. Hyper-mitogenic drive coexists with mitotic incompetence in senescent cells. Cell Cycle. 2012;11:4642-9 pubmed publisher..We conclude that cellular senescence is characterized by futile hyper-mitogenic drive associated with mTOR-dependent mitotic incompetence. ..
- Brown K, Xie S, Qiu X, Mohrin M, Shin J, Liu Y, et al. SIRT3 reverses aging-associated degeneration. Cell Rep. 2013;3:319-27 pubmed publisher..Our study illuminates the plasticity of mitochondrial homeostasis controlling stem cell and tissue maintenance during the aging process and shows that aging-associated degeneration can be reversed by a sirtuin. ..
- Burd C, Sorrentino J, Clark K, Darr D, Krishnamurthy J, Deal A, et al. Monitoring tumorigenesis and senescence in vivo with a p16(INK4a)-luciferase model. Cell. 2013;152:340-51 pubmed publisher..This work suggests that p16(INK4a) activation is a characteristic of all emerging cancers, making the p16(LUC) allele a sensitive, unbiased reporter of neoplastic transformation. ..
- Dellago H, Preschitz Kammerhofer B, Terlecki Zaniewicz L, Schreiner C, Fortschegger K, Chang M, et al. High levels of oncomiR-21 contribute to the senescence-induced growth arrest in normal human cells and its knock-down increases the replicative lifespan. Aging Cell. 2013;12:446-58 pubmed publisher..Therefore, we propose that miR-21 is the first miRNA that upon its knock-down extends the replicative lifespan of normal human cells. ..
- Liu L, Cheung T, Charville G, Hurgo B, Leavitt T, Shih J, et al. Chromatin modifications as determinants of muscle stem cell quiescence and chronological aging. Cell Rep. 2013;4:189-204 pubmed publisher..These findings highlight the importance of chromatin mapping in understanding unique features of stem cell identity and stem cell aging.
- Braumüller H, Wieder T, Brenner E, Aßmann S, Hahn M, Alkhaled M, et al. T-helper-1-cell cytokines drive cancer into senescence. Nature. 2013;494:361-5 pubmed publisher..Finally, as IFN-? and TNF induce senescence in numerous murine and human cancers, this may be a general mechanism for arresting cancer progression. ..
- Chandra T, Narita M. High-order chromatin structure and the epigenome in SAHFs. Nucleus. 2013;4:23-8 pubmed publisher..Evidence for the co-association of similar types of chromatin is emerging and SAHFs may provide a unique model system to study the correlation between HOCS and chromatin types, which are readily visible and regulable. ..
- Leontieva O, Paszkiewicz G, Demidenko Z, Blagosklonny M. Resveratrol potentiates rapamycin to prevent hyperinsulinemia and obesity in male mice on high fat diet. Cell Death Dis. 2013;4:e472 pubmed publisher..Given distinct mechanisms of action of rapamycin and resveratrol at clinically relevant doses, their combination warrants further investigation as a potential antiaging, antiobesity and antidiabetic modality. ..