Mammalian aging is complex and incompletely understood. Although significant effort has been spent addressing the genetics or, more recently, the pharmacology of aging, the toxicology of aging has been relatively understudied. Just as an understanding of 'carcinogens' has proven crucial to modern cancer biology, an understanding of environmental toxicants that accelerate aging ('gerontogens') will inform gerontology. In this review, we discuss the evidence for the existence of mammalian gerontogens, as well as describe the biomarkers needed to measure the age-promoting activity of a given toxicant. We focus on the effects of putative gerontogens on the in vivo accumulation of senescent cells, a characteristic feature of aging that has a causal role in some age-associated phenotypes.
Carcinoma of the gastrointestinal tract is the most common internal malignancy affecting men and women in Western countries. Chronic intestinal inflammation, especially of the colon, is also a Western disease and correlates with a significantly increased risk of developing cancer. This has suggested that the immune processes involved in both conditions might share some common pathways. Indeed, there is increasing evidence that phosphatidylinositol 3-kinases (PI 3-kinases) are involved in both the pathogenesis of colorectal carcinoma and intestinal inflammation. Here, we discuss this rapidly progressing area of research, presenting evidence for a pivotal role of PI 3-kinase(s) in intestinal pathophysiology.
WENDEL Yarbrough and colleagues (University of North Carolina at Chapel Hill, NC, USA) have made advances towards the treatment of head and neck cancer. 3-D cell-culture models that imitate the real structure of head and neck epithelium were used as recipients of adenovirus-mediated gene delivery. Epithelial cells in a monolayer were easy to infect due to the presence of the human coxsackie and adenovirus receptor (hCAR). However, the group noted that expression of hCAR was most prevalent in undifferentiated dividing cells, particularly oropharyngeal tumor cells. This raises the prospect of adenoviral gene delivery to these tumor sites without affecting surrounding non-cancerous cells. Furthermore, such a system may prove useful in treating severe cellular dysplasia, a precancerous condition in which hCAR expression is maintained. Yarbrough commented, ‘theoretically, in people at high risk for cancer, adenoviral gene therapy would only infect the precancerous sites and leave the normal, well differentiated sites alone’. (AR).
The elucidation of whole-genome sequences is expected to have a revolutionary impact on the discovery of novel medicines. With the availability of complete genome sequences of more than 30 different species, the field of antimicrobial drug discovery has the opportunity to access a remarkable diversity of genomic information. In this review, I summarize how microbial genomics has changed strategies of drug discovery by applying bioinformatics, novel genetic approaches and genomics-based technologies, including analysis of gene expression using DNA microarrays.
The prion diseases, including Creutzfeldt–Jakob disease (CJD) and Gerstmann–Straussler–Scheinker disease (GSS) in humans, and bovine spongiform encephalopathy (BSE) in cattle, can exhibit inherited, infectious and sporadic presentations. Moreover, inherited forms of these diseases can be infectious. Obviously, infectious diseases imply an exogenous exposure to a pathogen, whereas inherited diseases are associated with alterations to genomic DNA. To unify these apparently conflicting observations, Prusiner proposed that an endogenous prion protein was the infectious agent, and that mutated forms of this protein were responsible for inherited diseases. Subsequent work has identified the genomic sequence of the prion protein, the nature of the mutations associated with inherited disease, and the conformational distinction between the normal cellular isoform of the prion protein (PrPC) and its disease causing counterpart (PrPSc) (Reviewed in Ref. 1).
