Abstract: The disclosure provides seven DNAm-based estimators of plasma protein levels including those of plasminogen activation inhibitor 1 (PAI-1) and growth differentiation factor 15 (GDF15). The predictor of lifespan, DNAm GrimAge (in units of years), is a composite biomarker based on the seven DNAm surrogate markers and a DNAm-based estimator of smoking pack-years. These novel DNAm based biomarkers show the expected relationship with lifestyle factors (including healthy diet or educational attainment) and clinical biomarkers. Overall, these DNAm based biomarkers are expected to find many useful applications including human anti-aging studies.

Abstract: While methylation chips have been widely used in human studies over the last ten years, methylation chips for non-human species have not, perhaps due to lack of sufficient demand and/or because species specific methylation chips may be suboptimal for cross-species comparisons. To address challenges in this technology, we developed an algorithm, Conserved Methylation Array Probe Selector (CMAPS), which repurposes the degenerate base technology used to tolerate within-human variation to tolerate cross-species mutations. CMAPS performs a greedy search to obtain a maximal number of species that can be targeted using a probe for any CpG in the human genome, based on a multiple sequence alignment. CMAPS then ranks all the probes and chooses a final set so that arrays can be made that can query a large number of mammalian species and varied genomic positions based on external annotations of exons, CpG islands and hyper versus hypo methylated regions.

Abstract: The invention disclosed herein is a DNA methylation-based estimator of human telomere length (“DNAmTL”) that is based on 140 CpGs, and is applicable across the entire age spectrum. DNAmTL is even more strongly associated with chronological age than is measured TL (r˜?0.75 for DNAmTL versus r˜?0.35 for TL) and outperforms the latter in predicting i) time-to-death (P=4.1E-15), ii) time-to-coronary heart disease (p=6.6E-5), and iii) time-to-congestive heart failure (p=3.5E-6); all of which were corroborated with large sets of blood methylation data (N=6,850). DNAmTL is also associated with non-pathological conditions including physical functioning (P=7.6E-3), age-at-menopause (P=0.039), dietary variables (omega 3, fish, vegetable), educational attainment (P=4.3E-6) and income (P=3.1E-5). DNAmTL is an attractive molecular biomarker of aging due to its superior performance to measured TL, its intuitive interpretation of telomere length, its ease of use in vivo and in vitro, and its robustness.

Abstract: DNA methylation (DNAm) based biomarkers of aging have been developed for many tissues and organs. However, these biomarkers have sub-optimal accuracy in skin cells, fibroblasts and other cell types that are often used in ex vivo studies. To address this challenge, we analyzed DNA methylation array data sets derived from multiple sources of DNA, from which we developed a novel and highly robust DNAm age estimator (based on 391 CpGs) for human fibroblasts, keratinocytes, buccal cells, endothelial cells, lymphoblastoid cells, skin, blood, and saliva samples. The application of this new age estimator to ex vivo cell culture systems revealed that cellular population doubling is generally accompanied by an increase in epigenetic aging. The new skin & blood clock disclosed herein is useful for ex vivo and in vivo studies of human aging.

Abstract: Identifying reliable biomarkers of aging is a major goal in geroscience. While the first generation of epigenetic biomarkers of aging were developed using chronological age as a surrogate for biological age, we hypothesized that composite clinical measures of “phenotypic age”, may facilitate the development of a more powerful epigenetic biomarker of aging. Here we show that our newly developed epigenetic biomarker of aging “DNAm PhenoAge” strongly outperforms previous measure in regards to predictions for a variety of aging outcomes, including all-cause mortality, cancers, physical functioning, and, age-related dementia. It is also associated with Down syndrome, HIV infection, socioeconomic status, and various life style factors such as diet, exercise, and smoking. Overall, this single epigenetic biomarker of aging is able to capture risks for an array of diverse outcomes across multiple tissues and cells, and in moving forward, will facilitate the development of anti-aging interventions.

Abstract: A method for determining the epigenetic age acceleration of an individual comprising measuring a methylation level of a set of methylation markers in genomic DNA of an individual. An epigenetic age of the individual is determined based on the measured methylation level. An epigenetic age of the individual is further determined based on a methylation derived weighted average cell count of naive cytotoxic T cells and exhausted cytotoxic T cells in the individual. The determined epigenetic age is then compared to a chronological age of the individual to determine an epigenetic age acceleration of the individual. Instances wherein the epigenetic age is greater than the chronological age of the individual is an indication of an increased risk of all-cause mortality.

Abstract: The present invention provides methods comprising treating and/or preventing cognitive dysfunction in subjects infected with HIV by administering an antioxidant inflammation modulator (AIM). The present invention also provides for methods for treating and/or preventing an HIV-associated neurocognitive disorder by contacting peripheral blood monocytes of an HIV+subject with an AIM.

Abstract: A method for determining the age of a biological sample comprising measuring a methylation level of a set of methylation markers in genomic DNA of the biological sample. An age of the biological sample is determined with a statistical prediction algorithm, comprising (a) obtaining a linear combination of the methylation marker levels, and (b) applying a transformation to the linear combination to determine the age of the biological sample.

Abstract: An excess temperature and starting safety device for a magnetic centrifugal pump, having a rotor which delivers the medium and whose shaft terminates at a gap dish, where it bears permanent magnets driven by oppositely disposed permanent magnets which are connected to the shaft of the driving motor, while attached to the inner or outer surface of the gap dish is a conductor, more particularly a piece of wire of a thermocouple whose other conductor, closing the conductor circuit, is formed by the gap dish.