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From the moment of conception, we begin to age. A decay of cellular structures, gene regulation, and DNA sequence ages cells and organisms. DNA methylation patterns change with increasing age and contribute to age related disease. Here we identify 88 sites in or near 80 genes for which the degree of cytosine methylation is significantly correlated with age(More)
PURPOSE DNA damage recognition and repair play a major role in risk for breast cancer. We investigated 104 single nucleotide polymorphisms (SNP) in 17 genes whose protein products are involved in double-stranded break repair (DSBR). EXPERIMENTAL DESIGN We used a case-control design. Both the case individuals affected with breast cancer or with both breast(More)
MOTIVATION This article extends our recent research on penalized estimation methods in genome-wide association studies to the realm of rare variants. RESULTS The new strategy is tested on both simulated and real data. Our findings on breast cancer data replicate previous results and shed light on variant effects within genes. AVAILABILITY Rare variant(More)
OBJECTIVE To determine present practice for the management of glucocorticoid-induced osteoporosis (GIOP) in veterans; to characterize provider knowledge, beliefs, and practice behaviors regarding management of GIOP; and to identify potential barriers and interventions in the management of GIOP. METHODS To characterize current management of GIOP in an(More)
Patients with treated HIV-1-infection experience earlier occurrence of aging-associated diseases, raising speculation that HIV-1-infection, or antiretroviral treatment, may accelerate aging. We recently described an age-related co-methylation module comprised of hundreds of CpGs; however, it is unknown whether aging and HIV-1-infection exert negative health(More)
Cancer stem cells represent a novel therapeutic target. The major challenge in targeting leukemic stem cells (LSC) is finding therapies that largely spare normal hematopoietic stem cells (HSC) while eradicating quiescent LSCs. We present a mathematical model to predict how selective a therapy must be to ensure that enough HSCs survive when LSCs have been(More)
In this second article of our two-part review, we focus on age-associated physiologic changes involving the nervous, endocrine, hematologic, immune, and musculoskeletal systems, with close attention to the interconnected nature of these systems. There is a well-known connection between the neuroendocrine and immune systems via the(More)
In mice, clonal tracking of hematopoietic stem cells (HSCs) has revealed variations in repopulation characteristics. However, it is unclear whether similar properties apply in primates. Here, we examined this issue through tracking of thousands of hematopoietic stem and progenitor cells (HSPCs) in rhesus macaques for up to 12 years. Approximately half of(More)
A calculation of loss rates is reported for human structural and functional variables from a substantially larger data set than has been previously studied. Data were collected for healthy, nonsmoking human subjects of both sexes from a literature search of cross-sectional, longitudinal, and cross-sequential studies. The number of studies analyzed was 469,(More)
In this article, we discuss mechanisms responsible for the effects of heat treatment on increasing subsequent survival in the nematode worm Caenorhabditis elegans. We assume that the balance between damage associated with exposure to thermal stress and the level of heat shock proteins produced plays a key role in forming the age-pattern of mortality and(More)