Age-associated changes to the mammalian DNA methylome are well documented and thought to promote diseases of aging, such as cancer. Recent studies have identified collections of individual methylation sites whose aggregate methylation status measures chronological age, referred to as the DNA methylation clock. DNA methylation may also have value as a biomarker of healthy versus unhealthy aging and disease risk; in other words, a biological clock. Here we consider the relationship between the chronological and biological clocks, their underlying mechanisms, potential consequences, and their utility as biomarkers and as targets for intervention to promote healthy aging and longevity.

bInanimate surfaces, or fomites, can serve as routes of transmission of enteric and respiratory pathogens. No previous studies have evaluated the impact of surface disinfection on the level of pathogen transfer from fomites to fingers. Thus, the present study investigated the change in microbial transfer from contaminated fomites to fingers following disinfecting wipe use. Escherichia coli (10 8 to 10 9 CFU/ml), Staphylococcus aureus (10 9 CFU/ml), Bacillus thuringiensis spores (10 7 to 10 8 CFU/ml), and poliovirus 1 (10 8 PFU/ml) were seeded on ceramic tile, laminate, and granite in 10-l drops and allowed to dry for 30 min at a relative humidity of 15 to 32%. The seeded fomites were treated with a disinfectant wipe and allowed to dry for an additional 10 min. Fomite-to-finger transfer trials were conducted to measure concentrations of transferred microorganisms on the fingers after the disinfectant wipe intervention. The mean log 10 reduction of the test microorganisms on fomites by the disinfectant wipe treatment varied from 1.9 to 5.0, depending on the microorganism and the fomite. Microbial transfer from disinfectant-wipetreated fomites was lower (up to <0.1% on average) than from nontreated surfaces (up to 36.3% on average, reported in our previous study) for all types of microorganisms and fomites. This is the first study quantifying microbial transfer from contaminated fomites to fingers after the use of disinfectant wipe intervention. The data generated in the present study can be used in quantitative microbial risk assessment models to predict the effect of disinfectant wipes in reducing microbial exposure. Inanimate objects and surfaces (fomites) are known to be a reservoir for the transmission of pathogens in the environment directly, by surface contact with the mouth or abraded skin, or indirectly by contamination of fingers and subsequent hand-to-mouth, hand-toeye, or hand-to-nose contact (1, 2). Previous laboratory studies have modeled food preparation in domestic kitchens to better understand cross-contamination of food-borne pathogens (3, 4). The occurrence and spread of pathogens throughout the home and health care settings have also been studied to better understand the role of fomites in pathogen exposure and acquired infections (5-11). The potential for pathogen transfer from contaminated fomites to fingers is a concern in health care environments; particularly those in close proximity to the patient that are frequently touched (12-25). Health care-acquired infections caused by methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible S. aureus, and Clostridium difficile are associated with high morbidity and mortality (18,20,22,(26)(27)(28)(29)(30). Most nosocomial and foodborne pathogens can persist on fomites for weeks or even months (18,19,31,32) and on fingers for up to several hours (33-35). Pathogen presence and survival on fomites in domestic homes, public places, hospitals, and other health care facilities are important factors in evaluating potential health risks t...

Diffuse large B cell lymphoma (DLBCL) is an aggressive form of non-Hodgkin lymphoma. While the initial treatment strategy is highly effective, relapse occurs in 40% of cases. Histone deacetylase inhibitors (HDACi) are a promising class of anti-cancer drugs but their single agent efficacy against relapsed DLBCL has been variable, ranging from few complete/partial responses to some stable disease. However, most patients showed no response to HDACi monotherapy for unknown reasons. Here we show that sensitivity and resistance to the hydroxamate HDACi, PXD101, can be modeled in DLBCL cell lines. Sensitivity is characterized by G2/M arrest and apoptosis and resistance by reversible G1 growth arrest. These responses to PXD101 are independent of several negative prognostic indicators such as DLBCL subtype, BCL2 and MYC co-expression, and p53 mutation, suggesting that HDACi might be used effectively against highly aggressive DLBCL tumors if they are combined with other therapeutics that overcome HDACi resistance. Our investigation of mechanisms underlying HDACi resistance showed that cyclin-dependent kinase inhibitors (CKIs), p21 and p27, are upregulated by PXD101 in a sustained fashion in resistant cell lines concomitant with decreased activity of the cyclin E/cdk2 complex and decreased Rb phosphorylation. PXD101 treatment results in increased association of CKI with the cyclin E/cdk2 complex in resistant cell lines but not in a sensitive line, indicating that the CKIs play a key role in G1 arrest. The results suggest several treatment strategies that might increase the efficacy of HDACi against aggressive DLBCL.

Cellular senescence is a stable form of cell cycle arrest associated with proinflammatory responses. Senescent cells can be cleared by the immune system as a part of normal tissue homeostasis.