Section of Molecular Epidemiology

Rome, Italy

Section of Molecular Epidemiology

Rome, Italy
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Gunn D.A.,Unilever | De Craen A.J.M.,Leiden University | Dick J.L.,Unilever | Tomlin C.C.,Unilever | And 9 more authors.
Journals of Gerontology - Series A Biological Sciences and Medical Sciences | Year: 2013

Background.As facial appearance can be readily quantified and skin tissue easily accessed, they could be valuable tools for determining how biological mechanisms influence tissue degeneration with age and, consequently, human health and lifespan. It is unknown, however, whether appearance reflects disease risk or lifespan independently of factors already known to associate with both health and appearance.Methods.In a cross-sectional study, we compared the amount of skin wrinkling on a sun-protected site (upper inner arm) and the facial appearance of 261 offspring (mean age 63.2 y) of nonagenarian siblings with 253 age-matched controls (mean age 62.7 y), all with no reported disease history. We next examined whether any appearance features that significantly associated with familial longevity also associated with the Framingham cardiovascular disease (CVD) risk score. All analyses were adjusted for chronological age, smoking, photodamage, and body mass index.Results.Female and male offspring had reduced upper inner arm skin wrinkling (p =. 03 and p <. 001, respectively), and the male offspring looked 1.4 y younger than the controls (p =. 002). There were no significant associations between CVD risk and upper inner arm skin wrinkling. Women in the lowest quartile of CVD risk looked more than 2 y younger for their age than those in higher risk quartiles (p =. 002). Systolic blood pressure was the most significant (p =. 004) CVD risk factor that was associated with perceived age in women.Conclusions.Facial appearance and skin wrinkling at a sun-protected site reflect the propensity to reach an extreme old age, and facial appearance reflects the risk of succumbing to CVD independently of chronological age, smoking, photodamage, and BMI. © 2012 The Author. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.


Lupari E.,Section of Molecular Epidemiology | Ventura I.,Section of Experimental and Computational Carcinogenesis | Marcon F.,Instituto Superiore Of Sanita | Aquilina G.,Section of Experimental and Computational Carcinogenesis | And 2 more authors.
DNA Repair | Year: 2012

To maintain genomic integrity cells have to respond properly to a variety of exogenous and endogenous sources of DNA damage. DNA integrity is maintained by the coordinated action of DNA damage response mechanisms and DNA repair. In addition, there are also mechanisms of damage tolerance, such as translesion synthesis (TLS), which are important for survival after DNA damage but are potentially error-prone. Here, we investigate the role of DNA polymerase κ (pol κ) in TLS across alkylated lesions by silencing this polymerase (pol) in human cells using transient small RNA interference. We show that human pol κ has a significant protective role against methyl nitrosourea (MNU)-associated cytotoxicity without affecting significantly mutagenicity. The increase in MNU-induced cytotoxicity when pol κ is down-regulated was affected by the levels of O 6-methylguanine DNA methyltransferase and fully abolished when mismatch repair (MMR) was defective. Following MNU treatment, the cell cycle profile was unaffected by the pol κ status. The downregulation of pol κ caused a severe delay in the onset of the second mitosis that was fully dependent on the presence of O 6-methylguanine (O 6-meGua) lesions. After MNU exposure, in the absence of pol κ, the frequency of sister chromatid exchanges was unaffected whereas the induction of RAD 51 foci increased. We propose that pol κ partially protects human cells from the MMR-dependent cytotoxicity of O 6-meGua lesions by restoring the integrity of replicated duplexes containing single-stranded gaps generated opposite O 6-meGua facilitated by RAD 51 binding. © 2012 Elsevier B.V.


PubMed | Section of Molecular Epidemiology
Type: Journal Article | Journal: DNA repair | Year: 2012

To maintain genomic integrity cells have to respond properly to a variety of exogenous and endogenous sources of DNA damage. DNA integrity is maintained by the coordinated action of DNA damage response mechanisms and DNA repair. In addition, there are also mechanisms of damage tolerance, such as translesion synthesis (TLS), which are important for survival after DNA damage but are potentially error-prone. Here, we investigate the role of DNA polymerase (pol ) in TLS across alkylated lesions by silencing this polymerase (pol) in human cells using transient small RNA interference. We show that human pol has a significant protective role against methyl nitrosourea (MNU)-associated cytotoxicity without affecting significantly mutagenicity. The increase in MNU-induced cytotoxicity when pol is down-regulated was affected by the levels of O6-methylguanine DNA methyltransferase and fully abolished when mismatch repair (MMR) was defective. Following MNU treatment, the cell cycle profile was unaffected by the pol status. The downregulation of pol caused a severe delay in the onset of the second mitosis that was fully dependent on the presence of O6-methylguanine ( O6-meGua) lesions. After MNU exposure, in the absence of pol , the frequency of sister chromatid exchanges was unaffected whereas the induction of RAD 51 foci increased. We propose that pol partially protects human cells from the MMR-dependent cytotoxicity of O6-meGua lesions by restoring the integrity of replicated duplexes containing single-stranded gaps generated opposite O6-meGua facilitated by RAD 51 binding.

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