DNA Damage

Publication Title: 
The EMBO journal

Telomere loss has been proposed as a mechanism for counting cell divisions during aging in normal somatic cells. How such a mitotic clock initiates the intracellular signalling events that culminate in G1 cell cycle arrest and senescence to restrict the lifespan of normal human cells is not known. We investigated the possibility that critically short telomere length activates a DNA damage response pathway involving p53 and p21(WAF1) in aging cells.

Author(s): 
Vaziri, H.
West, M. D.
Allsopp, R. C.
Davison, T. S.
Wu, Y. S.
Arrowsmith, C. H.
Poirier, G. G.
Benchimol, S.
Publication Title: 
Mechanisms of Ageing and Development

Carnosine (beta-alanyl-L-histidine), an abundant naturally-occurring dipeptide has been shown to exhibit anti-ageing properties towards cultured cells, possibly due in part to its antioxidant/free radical scavenging abilities. In this paper the results of an investigation on the effects of carnosine, at the physiological concentration of 20 mM, on oxidative DNA damage levels and in vitro lifespan in peripheral blood derived human CD4+ T cell clones are reported.

Author(s): 
Hyland, P.
Duggan, O.
Hipkiss, A.
Barnett, C.
Barnett, Y.
Publication Title: 
Biogerontology

Biogerontology is the study of the aging of biological systems. This review addresses the relationship between chemistry and biology during aging, proposing that chemistry is responsible for the aging of biological systems. In the continuing struggle between chemistry and biology, chemistry is always the short-term, tactical winner--death of the individual is inevitable. However, barring the extinction of species, biology is the long-term, strategic victor--life survives, and the struggle continues.

Author(s): 
Baynes, J. W.
Publication Title: 
International Journal of Oncology

Retroviral infection of hTERT, the catalytic component of telomerase, into BJ fibroblasts (population doubling 28) resulted in reconstitution of telomerase activity, telomere maintenance, and extension of in vitro lifespan. The hTERT-infected cells also exhibited increased growth rate and colony forming efficiency relative to controls, while remaining contact-inhibited and maintaining a p53-mediated damage response following gamma-irradiation.

Author(s): 
Forsythe, Heidi L.
Elmore, Lynne W.
Jensen, Keith O.
Landon, Melissa R.
Holt, Shawn E.
Publication Title: 
The EMBO journal

Telomere shortening in normal human cells causes replicative senescence, a p53-dependent growth arrest state, which is thought to represent an innate defence against tumour progression. However, although it has been postulated that critical telomere loss generates a 'DNA damage' signal, the signalling pathway(s) that alerts cells to short dysfunctional telomeres remains only partially defined.

Author(s): 
Gire, VÈronique
Roux, Pierre
Wynford-Thomas, David
Brondello, Jean-Marc
Dulic, Vjekoslav
Publication Title: 
Nature Cell Biology

The nicotinamide adenine dinucleotide (NAD)-dependent deacetylase Sir2 (silent information regulator 2) regulates gene silencing in yeast and promotes lifespan extension during caloric restriction. The mammalian homologue of Sir2 (SirT1) regulates p53, NF-kappaB and Forkhead transcription factors, and is implicated in stress response. This report shows that the cell-cycle and apoptosis regulator E2F1 induces SirT1 expression at the transcriptional level. Furthermore, SirT1 binds to E2F1 and inhibits E2F1 activities, forming a negative feedback loop.

Author(s): 
Wang, Chuangui
Chen, Lihong
Hou, Xinghua
Li, Zhenyu
Kabra, Neha
Ma, Yihong
Nemoto, Shino
Finkel, Toren
Gu, Wei
Cress, W. Douglas
Chen, Jiandong
Publication Title: 
Nature

XPF-ERCC1 endonuclease is required for repair of helix-distorting DNA lesions and cytotoxic DNA interstrand crosslinks. Mild mutations in XPF cause the cancer-prone syndrome xeroderma pigmentosum. A patient presented with a severe XPF mutation leading to profound crosslink sensitivity and dramatic progeroid symptoms. It is not known how unrepaired DNA damage accelerates ageing or its relevance to natural ageing. Here we show a highly significant correlation between the liver transcriptome of old mice and a mouse model of this progeroid syndrome.

Author(s): 
Niedernhofer, Laura J.
Garinis, George A.
Raams, Anja
Lalai, Astrid S.
Robinson, Andria Rasile
Appeldoorn, Esther
Odijk, Hanny
Oostendorp, Roos
Ahmad, Anwaar
van Leeuwen, Wibeke
Theil, Arjan F.
Vermeulen, Wim
van der Horst, Gijsbertus T. J.
Meinecke, Peter
Kleijer, Wim J.
Vijg, Jan
Jaspers, Nicolaas G. J.
Hoeijmakers, Jan H. J.
Publication Title: 
Gan to Kagaku Ryoho. Cancer & Chemotherapy

When we discuss advances in longevity research during lectures and seminars, the question of the deciding factor for longevity often comes up. Even without looking at examples of research in molecular biology research, it is obvious to most that genetics play a major factor in longevity. The longest-lived human recorded was a French woman named Jeanne Calment, who died at age 122. All her family was long-lived. The quest for the identification of longevity genes by studying centenarian families has been explored for a decade, but no bona-fide longevity gene was identified.

Author(s): 
Shimizu, Takahiko
Shirasawa, Takuji
Publication Title: 
The Biochemical Journal

The free radical theory of aging proposes that ROS (reactive oxygen species) are major driving forces of aging, and are also critically involved in cellular senescence. Besides the mitochondrial respiratory chain, alternative sources of ROS have been described that might contribute to cellular senescence. Noxs (NADPH oxidases) are well-known sources of superoxide, which contribute to the antimicrobial capabilities of macrophages, a process involving the prototypical member of the family referred to as Nox2.

Author(s): 
Lener, Barbara
Kozie?, Rafa?
Pircher, Haymo
H¸tter, Eveline
Greussing, Ruth
Herndler-Brandstetter, Dietmar
Hermann, Martin
Unterluggauer, Hermann
Jansen-D¸rr, Pidder
Publication Title: 
Life Sciences

AIMS: Resveratrol, a silent information regulator 1 (SIRT1) activator, has been reported to act as an antioxidant contained in red wine and prevent the development of cardiovascular diseases. Histone deacetylase such as SIRT1 is involved in the regulation of lifespan extension. In this study, the effect of resveratrol on matrix metalloproteinases (MMPs) that play an important role in metastasis was examined in human fibrosarcoma cell line, HT1080. MAIN METHODS: The effect of resveratrol on MMPs' activity was evaluated using gelatin zymography.

Author(s): 
Lee, Soo-Jin
Kim, Moon-Moo

Pages

Subscribe to RSS - DNA Damage