Background Although telomere shortening occurs as a natural part of aging, there is now a robust body of research that suggests that there is a relationship between psychosocial, environmental, and behavioral factors and changes in telomere length. These factors need to be considered when integrating telomere measurement in biobehavioral research studies. Objectives This article provides a brief summary of the known facts about telomere biology and an integrative review of current human research studies that assessed relationships between psychosocial, environmental, or behavioral factors and telomere length. Methods An integrative review was conducted to examine human research studies that focused on psychosocial, environmental, and behavioral factors affecting telomere length and telomerase activity using the electronic databases PubMed/Medline and CINAHL from 2003 to the present. In addition to the known individual factors that are associated with telomere length, the results of the integrative review suggest that perceived stress, childhood adversities, major depressive disorder, educational attainment, physical activity, and sleep duration should also be measured. Discussion Multiple factors have been shown to affect telomere length. To advance understanding of the role of telomere length in health and disease risk, it will be important to further elucidate the mechanisms that contribute to telomere shortening.

Insulin-like growth factor-binding protein-3 (IGFBP-3), a major regulator of endocrine actions of IGFs, is a p53-regulated potent apoptotic factor and is significantly suppressed in a variety of cancers. Recent epidemiologic studies suggest that IGFBP-3 contributes to cancer risk protection in a variety of cancers, and a polymorphic variation of IGFBP-3 influences cancer risk, although other studies vary in their conclusions. Some antiproliferative actions of IGFBP-3 have been reported to be independent of IGFs, but the precise biochemical/molecular mechanisms of IGF-independent, antiproliferative actions of IGFBP-3 are largely unknown. Here we report a new cell death receptor, IGFBP-3R, that is a singlespan membrane protein and binds specifically to IGFBP-3 but not other IGFBP species. Expression analysis of IGFBP-3 and IGFBP-3R indicates that the IGFBP-3/IGFBP-3R axis is impaired in breast and prostate cancer. We also provide evidence for anti-tumor effect of IGFBP-3R in vivo using prostate and breast cancer xenografts in athymic nude mice. Further in vitro studies demonstrate that IGFBP-3R mediates IGFBP-3-induced caspase-8-dependent apoptosis in various cancer cells. Knockdown of IGFBP-3R attenuated IGFBP-3-induced caspase activities and apoptosis, whereas overexpression of IGFBP-3R enhanced IGFBP-3 biological effects. IGFBP-3R physically interacts and activates caspase-8, and knockdown of caspase-8 expression or activity inhibited IGFBP-3/IGFBP-3R-induced apoptosis. Here, we propose that IGFBP-3R represents a novel cell death receptor and is essential for the IGFBP-3-induced apoptosis and tumor suppression. Thus, the IGFBP-3/IGFBP-3R axis may provide therapeutic and prognostic value for the treatment of cancer.Insulin-like growth factor-binding proteins (IGFBPs) 3 are integral components of the IGF system and modulate biological actions of IGFs such as cellular proliferation, differentiation, increase in metabolic activity, and cell survival (1). Apart from its ability to inhibit or enhance IGF actions, all the IGFBPs, IGFBP-1 to -6, have been reported to exert distinct biological actions such as cell proliferation, differentiation, migration, angiogenesis, and apoptosis through an IGF/IGF-I receptor (IGF-IR)-independent manner (2-7). These intrinsic biological activities of IGFBPs appear to be critical to cardiogenesis, vascular development, and pathogenesis of cancer.IGFBP-3, the most abundant IGFBP species in serum, circulates as a 150-kDa ternary complex with an acid-labile subunit and IGF peptide (1-3). Classically, the principal function of IGFBP-3 has been to transport IGFs, protecting them from rapid clearance and/or degradation, and modulating IGF bioavailability to cell-surface IGF receptors (8 -9). Many studies have reported that IGFBP-3 exhibits distinct biological effects independent of the IGF/IGF-IR axis, in particular cell growth inhibition and induction of apoptosis in a variety of cancer cells (10 -14). IGFBP-3 was shown to exert its IGF/IGF-IR-independent, antiproliferative actions via ...

Background The exciting discovery that telomere shortening is associated with many health conditions, and that telomere lengths can be altered in response to social and environmental exposures, has underscored the need for methods to accurately and consistently quantify telomere length. Objectives The purpose of this paper is to provide a comprehensive summary that compares and contrasts the current technologies used to assess telomere length. Discussion Multiple methods have been developed for the study of telomeres. These techniques include quantification of telomere length by terminal restriction fragmentation—which was one of the earliest tools used for length assessment—making it the gold standard in telomere biology. Quantitative-PCR provides the advantage of being able to use smaller amounts of DNA, thereby making it amenable to epidemiology studies involving large numbers of people. An alternative method uses fluorescent probes to quantify not only mean telomere lengths, but also chromosome-specific telomere lengths; however, the downside of this approach is that it can only be used on mitotically active cells. Additional methods that permit assessment of the length of a subset of chromosome-specific telomeres, or the subset of telomeres that demonstrate shortening, are also reviewed. Conclusion Given the increased utility for telomere assessments as a biomarker in physiological, psychological and biobehavioral research, it is important that investigators become familiar with the methodological nuances of the various procedures used for measuring telomere length. This will ensure that they are empowered to select an optimal assessment approach to meet the needs of their study designs. Gaining a better understanding of the benefits and drawbacks of various measurement techniques is important not only in individual studies, but also to further establish the science of telomere associations with biobehavioral phenomena.