premature aging

Summary

Summary: Changes in the organism associated with senescence, occurring at an accelerated rate.

Top Publications

  1. Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink J, Rovio A, Bruder C, et al. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature. 2004;429:417-23 pubmed
    ..Our results thus provide a causative link between mtDNA mutations and ageing phenotypes in mammals...
  2. Park J, Cho M, Leonard S, Calder B, Mian I, Kim W, et al. Homeostatic imbalance between apoptosis and cell renewal in the liver of premature aging Xpd mice. PLoS ONE. 2008;3:e2346 pubmed publisher
    ..excision repair and transcription due to a mutation in the Xpd gene (R722W), display severe symptoms of premature aging but have a reduced incidence of cancer...
  3. Pereira S, Bourgeois P, Navarro C, Esteves Vieira V, Cau P, De Sandre Giovannoli A, et al. HGPS and related premature aging disorders: from genomic identification to the first therapeutic approaches. Mech Ageing Dev. 2008;129:449-59 pubmed publisher
    ..In these syndromes, premature aging is defined as "segmental" since only some of its features are accelerated...
  4. Varela I, Pereira S, Ugalde A, Navarro C, Suarez M, Cau P, et al. Combined treatment with statins and aminobisphosphonates extends longevity in a mouse model of human premature aging. Nat Med. 2008;14:767-72 pubmed publisher
    ..Likewise, the longevity of these mice is substantially extended. These findings open a new therapeutic approach for human progeroid syndromes associated with nuclear-envelope abnormalities...
  5. Flores E, Sengupta S, Miller J, Newman J, Bronson R, Crowley D, et al. Tumor predisposition in mice mutant for p63 and p73: evidence for broader tumor suppressor functions for the p53 family. Cancer Cell. 2005;7:363-73 pubmed
    ..These findings provide evidence for a broader role for the p53 family than has been previously reported...
  6. Mohaghegh P, Hickson I. Premature aging in RecQ helicase-deficient human syndromes. Int J Biochem Cell Biol. 2002;34:1496-501 pubmed
    ..These disorders are associated with cancer predisposition and/or premature aging. In Bloom's syndrome, affected individuals are predisposed to many types of cancer at an early age...
  7. Tsujikawa H, Kurotaki Y, Fujimori T, Fukuda K, Nabeshima Y. Klotho, a gene related to a syndrome resembling human premature aging, functions in a negative regulatory circuit of vitamin D endocrine system. Mol Endocrinol. 2003;17:2393-403 pubmed
    ..These observations suggest that klotho may participate in a negative regulatory circuit of the vitamin D endocrine system, through the regulation of 1alpha-hydroxylase gene expression...
  8. Vogelmeier C, Bals R. Chronic obstructive pulmonary disease and premature aging. Am J Respir Crit Care Med. 2007;175:1217-8 pubmed
  9. Huang J, Lemire B. Mutations in the C. elegans succinate dehydrogenase iron-sulfur subunit promote superoxide generation and premature aging. J Mol Biol. 2009;387:559-69 pubmed publisher
    ..Our work leads to a better understanding of the relationship between genotype and phenotype in respiratory chain mutations and of the mechanisms of aging and tumorigenesis...

More Information

Publications62

  1. Vermulst M, Wanagat J, Kujoth G, Bielas J, Rabinovitch P, Prolla T, et al. DNA deletions and clonal mutations drive premature aging in mitochondrial mutator mice. Nat Genet. 2008;40:392-4 pubmed publisher
    ..Here we identify mtDNA deletions as a driving force behind the premature aging phenotype of mitochondrial mutator mice, and provide evidence for a homology-directed DNA repair mechanism in ..
  2. Wang L, Yang L, Debidda M, Witte D, Zheng Y. Cdc42 GTPase-activating protein deficiency promotes genomic instability and premature aging-like phenotypes. Proc Natl Acad Sci U S A. 2007;104:1248-53 pubmed
    ..level in diverse tissues of adult mice; significantly shortened life span of the animals; and multiple premature aging-like phenotypes, including a reduction in body mass, a loss of subdermal adipose tissue, severe lordokyphosis,..
  3. Capell B, Collins F. Human laminopathies: nuclei gone genetically awry. Nat Rev Genet. 2006;7:940-52 pubmed
  4. Coppede F, Migliore L. DNA repair in premature aging disorders and neurodegeneration. Curr Aging Sci. 2010;3:3-19 pubmed
    The accumulation of DNA damage has been widely implicated in premature aging and neurodegeneration...
  5. Razzaque M, Lanske B. Hypervitaminosis D and premature aging: lessons learned from Fgf23 and Klotho mutant mice. Trends Mol Med. 2006;12:298-305 pubmed
    ..These mice develop identical phenotypes consistent with premature aging. Elimination or reduction of vitamin-D activity from Fgf23 and Kl mutant mice, either by dietary restriction ..
  6. Stadler K, Jenei V, von Bölcsházy G, Somogyi A, Jakus J. Increased nitric oxide levels as an early sign of premature aging in diabetes. Free Radic Biol Med. 2003;35:1240-51 pubmed
    ..High peroxynitrite generation suggested the onset of processes characteristic to premature aging of the endothelium...
  7. Chang S, Multani A, Cabrera N, Naylor M, Laud P, Lombard D, et al. Essential role of limiting telomeres in the pathogenesis of Werner syndrome. Nat Genet. 2004;36:877-82 pubmed
    ..Mutational inactivation of the gene WRN causes Werner syndrome, an autosomal recessive disease characterized by premature aging, elevated genomic instability and increased cancer incidence...
  8. Bachrati C, Hickson I. RecQ helicases: suppressors of tumorigenesis and premature aging. Biochem J. 2003;374:577-606 pubmed
    ..human RecQ helicases give rise to defined genetic disorders associated with cancer predisposition and/or premature aging. These are Bloom's syndrome, Werner's syndrome and Rothmund-Thomson syndrome, which are caused by defects in ..
  9. Ichikawa K, Noda T, Furuichi Y. [Preparation of the gene targeted knockout mice for human premature aging diseases, Werner syndrome, and Rothmund-Thomson syndrome caused by the mutation of DNA helicases]. Nihon Yakurigaku Zasshi. 2002;119:219-26 pubmed
    ..BLM, WRN, and RTS helicases are responsible for distinct but overlapping clinical features suggesting premature aging and an enhanced risk of cancer, which apparently stems from chromosomal instability in the cells of tissues ..
  10. Heuser I. Depression, endocrinologically a syndrome of premature aging?. Maturitas. 2002;41 Suppl 1:S19-23 pubmed
  11. Caron Debarle M, Lagathu C, Boccara F, Vigouroux C, Capeau J. HIV-associated lipodystrophy: from fat injury to premature aging. Trends Mol Med. 2010;16:218-29 pubmed publisher
    ..lipodystrophy are responsible for increased cardiovascular and hepatic risks and could also participate in premature aging. We propose that adipose tissue injury by HIV and cART induces fat hypertrophy or atrophy and contributes to ..
  12. Broers J, Ramaekers F, Bonne G, Yaou R, Hutchison C. Nuclear lamins: laminopathies and their role in premature ageing. Physiol Rev. 2006;86:967-1008 pubmed
    ..It is concluded that lamins seem to be key players in, among others, controlling the process of cellular ageing, since disturbance in lamin protein structure gives rise to several forms of premature ageing...
  13. Chen Y, Kao C, Chen Y, Wang C, Wu C, Tsai C, et al. Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice. Genes Dev. 2009;23:1183-94 pubmed publisher
    ..of nerve and muscle degeneration; together, they lead to a panel of phenotypic features suggestive of premature aging. Our study also reveals that Cisd2 is primarily localized in the mitochondria and that mitochondrial ..
  14. Keisala T, Minasyan A, Lou Y, Zou J, Kalueff A, Pyykko I, et al. Premature aging in vitamin D receptor mutant mice. J Steroid Biochem Mol Biol. 2009;115:91-7 pubmed publisher
    Hypervitaminosis vitamin D(3) has been recently implicated in premature aging through the regulation of 1alpha hydroxylase expression by klotho and fibroblast growth factor-23 (Fgf-23)...
  15. Shimada T, Takeshita Y, Murohara T, Sasaki K, Egami K, Shintani S, et al. Angiogenesis and vasculogenesis are impaired in the precocious-aging klotho mouse. Circulation. 2004;110:1148-55 pubmed
    ..We examined whether ischemia-induced angiogenesis/vasculogenesis is altered in klotho (kl) mutant mice, an animal model of typical aging...
  16. Antoch M, Gorbacheva V, Vykhovanets O, Toshkov I, Kondratov R, Kondratova A, et al. Disruption of the circadian clock due to the Clock mutation has discrete effects on aging and carcinogenesis. Cell Cycle. 2008;7:1197-204 pubmed
    ..They also highlight the existence of a complex interconnection between ageing, carcinogenesis and individual components of the circadian clock machinery...
  17. Hasty P, Vijg J. Accelerating aging by mouse reverse genetics: a rational approach to understanding longevity. Aging Cell. 2004;3:55-65 pubmed
    ..This may be in keeping with the recent discovery of a possible 'universal survival' pathway that improves antioxidant defence and genome maintenance and simultaneously extends lifespan in the mouse and several invertebrate species...
  18. Hasty P, Campisi J, Hoeijmakers J, van Steeg H, Vijg J. Aging and genome maintenance: lessons from the mouse?. Science. 2003;299:1355-9 pubmed
    ..Maintaining genome integrity has emerged as a major factor in longevity and cell viability. Here we discuss the use of mouse models with defects in genome maintenance for understanding the molecular basis of aging in humans...
  19. Brosh R, Bohr V. Human premature aging, DNA repair and RecQ helicases. Nucleic Acids Res. 2007;35:7527-44 pubmed
    ..is of particular interest since several human RecQ helicases are defective in diseases associated with premature aging and cancer...
  20. Mariño G, Ugalde A, Salvador Montoliu N, Varela I, Quirós P, Cadinanos J, et al. Premature aging in mice activates a systemic metabolic response involving autophagy induction. Hum Mol Genet. 2008;17:2196-211 pubmed publisher
    ..On the basis of these results, we propose that nuclear abnormalities causing premature aging in Zmpste24(-/-) mice trigger a metabolic response involving the activation of autophagy...
  21. Muñoz P, Blanco R, Flores J, Blasco M. XPF nuclease-dependent telomere loss and increased DNA damage in mice overexpressing TRF2 result in premature aging and cancer. Nat Genet. 2005;37:1063-71 pubmed
    ..Finally, we show that a number of human skin tumors have increased expression of TRF2, further highlighting a role for TRF2 in skin cancer...
  22. BEAUDRY V, Attardi L. SKP-ing TAp63: stem cell depletion, senescence, and premature aging. Cell Stem Cell. 2009;5:1-2 pubmed publisher
    ..In this issue of Cell Stem Cell, by generating isoform-specific knockout mice, Su et al. (2009) reveal pivotal roles for TAp63 in the maintenance of dermal and epidermal precursors, genomic stability, and organismal longevity...
  23. Cordisco S, Maurelli R, Bondanza S, Stefanini M, Zambruno G, Guerra L, et al. Bmi-1 reduction plays a key role in physiological and premature aging of primary human keratinocytes. J Invest Dermatol. 2010;130:1048-62 pubmed publisher
    ..cultures from young and old healthy donors, and from young patients with inherited defects leading to premature aging, we demonstrated that p16(INK4a) is a reliable marker of both physiological and premature epidermal aging...
  24. Vijg J. Somatic mutations and aging: a re-evaluation. Mutat Res. 2000;447:117-35 pubmed
    ..New strategies for investigating the relationship between genome instability, mutation accumulation and aging will be discussed...
  25. Agrelo R, Cheng W, Setien F, Ropero S, Espada J, Fraga M, et al. Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer. Proc Natl Acad Sci U S A. 2006;103:8822-7 pubmed
    ..These findings highlight the importance of WRN epigenetic inactivation in human cancer, leading to enhanced chromosomal instability and hypersensitivity to chemotherapeutic drugs...
  26. Kondratov R, Kondratova A, Gorbacheva V, Vykhovanets O, Antoch M. Early aging and age-related pathologies in mice deficient in BMAL1, the core componentof the circadian clock. Genes Dev. 2006;20:1868-73 pubmed
    ..Here we report that Bmal1(-/-) mice have reduced lifespans and display various symptoms of premature aging including sarcopenia, cataracts, less subcutaneous fat, organ shrinkage, and others...
  27. Su X, Paris M, Gi Y, Tsai K, Cho M, Lin Y, et al. TAp63 prevents premature aging by promoting adult stem cell maintenance. Cell Stem Cell. 2009;5:64-75 pubmed publisher
    ..These data indicate that TAp63 serves to maintain adult skin stem cells by regulating cellular senescence and genomic stability, thereby preventing premature tissue aging...
  28. Kraytsberg Y, Simon D, Turnbull D, Khrapko K. Do mtDNA deletions drive premature aging in mtDNA mutator mice?. Aging Cell. 2009;8:502-6 pubmed publisher
    ..Recent research has demonstrated that relatively higher levels of mtDNA deletions correlate with premature aging in mtDNA mutator mice, which led to the conclusion that premature aging in these mice is driven by mtDNA ..
  29. Keyes W, Wu Y, Vogel H, Guo X, Lowe S, Mills A. p63 deficiency activates a program of cellular senescence and leads to accelerated aging. Genes Dev. 2005;19:1986-99 pubmed
    ..Our results thus suggest a causative link between cellular senescence and aging in vivo, and demonstrate that p63 deficiency accelerates this process...
  30. Baeza I, De Castro N, Gimenez Llort L, de la Fuente M. Ovariectomy, a model of menopause in rodents, causes a premature aging of the nervous and immune systems. J Neuroimmunol. 2010;219:90-9 pubmed publisher
    ..Therefore, ovariectomy deteriorates homeostasis and may be a model of premature aging.
  31. Kondratov R, Vykhovanets O, Kondratova A, Antoch M. Antioxidant N-acetyl-L-cysteine ameliorates symptoms of premature aging associated with the deficiency of the circadian protein BMAL1. Aging (Albany NY). 2009;1:979-87 pubmed
    Deficiency of the circadian clock protein BMAL1 leads to premature aging and increased levels of reactivate oxygen species in several tissues of mice...
  32. Robinson L, Karlsson N, Weiss A, Packer N. Proteomic analysis of the genetic premature aging disease Hutchinson Gilford progeria syndrome reveals differential protein expression and glycosylation. J Proteome Res. 2003;2:556-7 pubmed
    Proteomics has revealed differential protein expression and glycosylation in membrane proteins from premature aging Hutchinson-Gilford progeria syndrome fibroblasts (progeria)...
  33. de Boer J, Andressoo J, de Wit J, Huijmans J, Beems R, van Steeg H, et al. Premature aging in mice deficient in DNA repair and transcription. Science. 2002;296:1276-9 pubmed
    ..TTD mice were found to exhibit many symptoms of premature aging, including osteoporosis and kyphosis, osteosclerosis, early greying, cachexia, infertility, and reduced life-..
  34. Edgar D, Shabalina I, Camara Y, Wredenberg A, Calvaruso M, Nijtmans L, et al. Random point mutations with major effects on protein-coding genes are the driving force behind premature aging in mtDNA mutator mice. Cell Metab. 2009;10:131-8 pubmed publisher
    ..of point mutations and linear deletions of mtDNA causing a progressive respiratory chain dysfunction and a premature aging phenotype...
  35. Hagelstrom R, Blagoev K, Niedernhofer L, Goodwin E, Bailey S. Hyper telomere recombination accelerates replicative senescence and may promote premature aging. Proc Natl Acad Sci U S A. 2010;107:15768-73 pubmed publisher
    ..syndrome result from defects in the RecQ helicases Werner (WRN) and Bloom (BLM), respectively, and display premature aging phenotypes. Similarly, XFE progeroid syndrome results from defects in the ERCC1-XPF DNA repair endonuclease...
  36. Lahoute C, Sotiropoulos A, Favier M, Guillet Deniau I, Charvet C, Ferry A, et al. Premature aging in skeletal muscle lacking serum response factor. PLoS ONE. 2008;3:e3910 pubmed publisher
    ..Altogether, these results suggest that a naturally occurring SRF down-regulation precedes and contributes to the muscle aging process. Indeed, triggering SRF loss in the muscles of mutant mice results in an accelerated aging process...
  37. Tyner S, Venkatachalam S, Choi J, Jones S, Ghebranious N, Igelmann H, et al. p53 mutant mice that display early ageing-associated phenotypes. Nature. 2002;415:45-53 pubmed
    ..A second line of transgenic mice containing a temperature-sensitive mutant allele of p53 also exhibits early ageing phenotypes. These data suggest that p53 has a role in regulating organismal ageing...
  38. Lanske B, Razzaque M. Premature aging in klotho mutant mice: cause or consequence?. Ageing Res Rev. 2007;6:73-9 pubmed
    ..identified that fibroblast growth factor 23 (Fgf-23) null mice and klotho hypomorphs could generate multiple premature aging-like features, including shortened lifespan, infertility, kyphosis, atherosclerosis, extensive soft tissue ..
  39. Sun L, Lee D, Zhang Q, Xiao W, Raabe E, Meeker A, et al. Growth retardation and premature aging phenotypes in mice with disruption of the SNF2-like gene, PASG. Genes Dev. 2004;18:1035-46 pubmed
    ..that facilitates DNA methylation, causes global hypomethylation, developmental growth retardation and a premature aging phenotype...
  40. Plasilova M, Chattopadhyay C, Pal P, Schaub N, Buechner S, Mueller H, et al. Homozygous missense mutation in the lamin A/C gene causes autosomal recessive Hutchinson-Gilford progeria syndrome. J Med Genet. 2004;41:609-14 pubmed
  41. Vijg J, Suh Y. Ageing: chromatin unbound. Nature. 2006;440:874-5 pubmed
  42. Douglas R, Haddad G. Can O2 dysregulation induce premature aging?. Physiology (Bethesda). 2008;23:333-49 pubmed publisher
    ..the ability to respond adequately to various stressors is hampered, and this is traditionally defined as premature aging or senescence...
  43. Liu B, Wang J, Chan K, Tjia W, Deng W, Guan X, et al. Genomic instability in laminopathy-based premature aging. Nat Med. 2005;11:780-5 pubmed
    b>Premature aging syndromes often result from mutations in nuclear proteins involved in the maintenance of genomic integrity. Lamin A is a major component of the nuclear lamina and nuclear skeleton...
  44. Cadinanos J, Varela I, Lopez Otin C, Freije J. From immature lamin to premature aging: molecular pathways and therapeutic opportunities. Cell Cycle. 2005;4:1732-5 pubmed
    ..Moreover, p53 nullizygosity allows a modest but significant improvement in the premature aging phenotype, and contributes to delaying the onset of the progeroid condition...
  45. Razzaque M, Sitara D, Taguchi T, St Arnaud R, Lanske B. Premature aging-like phenotype in fibroblast growth factor 23 null mice is a vitamin D-mediated process. FASEB J. 2006;20:720-2 pubmed
    ..Fgf-23-/-) have a short lifespan and show numerous biochemical and morphological features consistent with premature aging-like phenotypes, including kyphosis, severe muscle wasting, hypogonadism, osteopenia, emphysema, ..
  46. Brown Borg H, Rakoczy S. Catalase expression in delayed and premature aging mouse models. Exp Gerontol. 2000;35:199-212 pubmed
  47. Chang S. A mouse model of Werner Syndrome: what can it tell us about aging and cancer?. Int J Biochem Cell Biol. 2005;37:991-9 pubmed
    ..to dysfunctional telomeres have been proposed to promote replicative senescence that impact upon the onset of premature aging and cancer...
  48. Weidenheim K, Dickson D, Rapin I. Neuropathology of Cockayne syndrome: Evidence for impaired development, premature aging, and neurodegeneration. Mech Ageing Dev. 2009;130:619-36 pubmed publisher
    ..Understanding the genetics, biochemical, and cellular pathophysiology of these disorders remains fragmentary...
  49. Benson E, Zhao B, Sassoon D, Lee S, Aaronson S. Effects of p21 deletion in mouse models of premature aging. Cell Cycle. 2009;8:2002-4 pubmed
    ..abrogate signaling pathways known to induce cellular senescence and to assess the effects in mouse models of premature aging. Recently, we reported the effect of loss of function of p21, a gene implicated in p53-induced cellular ..
  50. Shumaker D, Dechat T, Kohlmaier A, Adam S, Bozovsky M, Erdos M, et al. Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging. Proc Natl Acad Sci U S A. 2006;103:8703-8 pubmed
    The premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS) is caused by a mutant lamin A (LADelta50). Nuclei in cells expressing LADelta50 are abnormally shaped and display a loss of heterochromatin...
  51. Khrapko K, Kraytsberg Y, de Grey A, Vijg J, Schon E. Does premature aging of the mtDNA mutator mouse prove that mtDNA mutations are involved in natural aging?. Aging Cell. 2006;5:279-82 pubmed
    ..mice with an increased rate of somatic point mutations in mitochondrial DNA (mtDNA mutator mice) display a premature aging phenotype reminiscent of human aging...
  52. Kuchinad A, Schweinhardt P, Seminowicz D, Wood P, Chizh B, Bushnell M. Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the brain?. J Neurosci. 2007;27:4004-7 pubmed
    ..Moreover, the regions in which we demonstrate objective changes may be functionally linked to core features of the disorder including affective disturbances and chronic widespread pain...
  53. Li H, Vogel H, Holcomb V, Gu Y, Hasty P. Deletion of Ku70, Ku80, or both causes early aging without substantially increased cancer. Mol Cell Biol. 2007;27:8205-14 pubmed
    ..Thus, our observations suggest that the Ku heterodimer is important for longevity assurance in mice since divergent genetic backgrounds and/or environments likely account for these previously reported differences...