GSTT1, GSTP1 and XPC genes are associated with longevity in an Italian cohort

Scarfò, Manuel; Sciandra, Chiara; Ruberto, Stefano; Santovito, Alfredo

doi:10.1080/03014460.2021.1985170

Cited by 4 publications

(3 citation statements)

References 41 publications

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“…Here, we found the top upregulated GO term was one often associated to longevity, healthy aging, and oxidative stress protection, namely, glutathione metabolic processes 38 ( Figure 2 E). These genes included glutathione S-transferase genes ( Gstm1 , Gsta3 , and Gsta4 ) ( Figure S2 H), an important family of detoxifying and cytoprotective enzymes crucial for longevity 39 and a protective mechanism against the development of renal fibrosis healthy aging and oxidative stress protection. Given the decrease in partial EMT observed in the in vitro model, we sought to assess how these molecular changes manifest themselves at the physiological level.…”

Section: Resultsmentioning

confidence: 99%

HDAC1/2 inhibitor therapy improves multiple organ systems in aged mice

Tammaro,

Daniels,

et al. 2024

iScience

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Section: Resultsmentioning

confidence: 99%

HDAC1/2 inhibitor therapy improves multiple organ systems in aged mice

Tammaro,

Daniels,

et al. 2024

iScience

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“…Here we found the top upregulated go term was one often associated to longevity and healthy aging, namely, glutathione metabolic processes 38 (Figure 2E). These genes included Glutathione S-Transferase genes (Gstm1, Gsta3, and Gsta4) (Supplemental Figure 2H), an important family of detoxifying and cytoprotective enzymes crucial for longevity 39 and as protective mechanism against the development of renal fibrosis 38,[40][41][42] . Given the decrease in partial EMT observed in the in vitro model, we sought to assess how these molecular changes manifest themselves at the physiological level.…”

Section: Cmpd60 In Aged Mice Restores Youthful Molecular and Physiolo...mentioning

confidence: 99%

Treatment with a selective histone deacetylase (HDAC) 1 and 2 inhibitor in aged mice rejuvenates multiple organ systems

Tammaro,

Daniels,

et al. 2023

Preprint

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The process of aging increases the risk of developing age-related diseases, which come at great societal healthcare costs and suffering to individuals. Meanwhile, targeting the basic mechanisms of aging can reduce the risk of developing age-related diseases during aging, essentially resulting in a ‘healthy aging’ process. Multiple aging pathways exist, which over past decades have systematically been confirmed through gene knockout or overexpression studies in mammals and the ability to increase healthy lifespan. In this work, we perform transcriptome-based drug screening to identify small molecules that mimic the transcriptional profiles of long-lived genetic interventions in mammals. We identify one small molecule whose transcriptional effects mimic diverse known genetic longevity interventions: compound 60 (Cmpd60), which is a selective inhibitor of histone deacetylase 1 (HDAC1) and 2 (HDAC2). In line with this, in a battery of molecular, phenotypic, and bioinformatic analyses, in multiple disease cell and animal models, we find that Cmpd60 treatment rejuvenates multiple organ systems. These included the kidney, brain, and heart. In renal aging, Cmpd60 reduced partial epithelial-mesenchymal transition (EMT)in vitroand decreased fibrosisin vivo. For the aging brain, Cmpd60 reduced dementia-related gene expressionin vivo, effects that were recapitulated when treating the APPSWE-1349 Alzheimer mouse. In cardiac aging, Cmpd60 treatment activated favorable developmental gene expressionin vivoand in line with this, improved ventricular cardiomyocyte contraction and relaxation in a cell model of cardiac hypertrophy. Our work establishes that a systemic, two-week treatment with an HDAC1/2 inhibitor serves as a multi-tissue, healthy aging intervention in mammals. This holds potential for translation towards therapeutics that promote healthy aging in humans.

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“…We genotyped all subjects for CYP1A1, GSTT1, GSTM1, XRCC1 Trp194Arg and XPC. Primers and methodologies were described in Scarfò et al 2021 [32].…”

Section: Dna Extraction and Polymorphism Analysismentioning

confidence: 99%

Sportive activity reduces genomic damage

Nota

Santovito

2022

Preprint

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Purpose - The influence of training on the levels of genomic damage are not univocal, and to date not completely understood. Indeed, studies in this area remain scant and do not draw definitive conclusions. Our aim was to evaluate the influence of training on the levels of DNA damage in young athletes. We also wanted to explore the possibility of genomic damage to be driven by single-gene polymorphisms on metabolic and DNA repair genes in our sample. Method - We compared the levels of Micronuclei and other nuclear aberrations in buccal mucosa cells of a group of 35 healthy, young martial artists with the ones of a group of 35 healthy, young sedentary controls. We also genotyped all subjects for three metabolic and two DNA repair genes in order to investigate the influence of the related single-gene polymorphisms on the frequency of genomic damage. Results - We observed a decrease in the levels of genomic damage in athletes relatively to sedentary controls; this decrease was significant in both Micronuclei ant Total Aberrations. Instead, single-gene polymorphisms did not alter significantly the levels of nuclear aberrations. Conclusion - The decrease in genomic damage observed in athletes suggests a protective effect of training and corroborates the beneficial effects of sportive activity on human health. Moreover, even other factors, such as the nature of the sport and training length, could influence the results.

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GSTT1, GSTP1 and XPC genes are associated with longevity in an Italian cohort

Cited by 4 publications

References 41 publications

HDAC1/2 inhibitor therapy improves multiple organ systems in aged mice

HDAC1/2 inhibitor therapy improves multiple organ systems in aged mice

Treatment with a selective histone deacetylase (HDAC) 1 and 2 inhibitor in aged mice rejuvenates multiple organ systems

Sportive activity reduces genomic damage

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