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Integrating the environmental and genetic architectures of aging and mortality

6 months 3 weeks ago
Both environmental exposures and genetics are known to play important roles in shaping human aging. Here we aimed to quantify the relative contributions of environment (referred to as the exposome) and genetics to aging and premature mortality. To systematically identify environmental exposures associated with aging in the UK Biobank, we first conducted an exposome-wide analysis of all-cause mortality (n = 492,567) and then assessed the associations of these exposures with a proteomic age clock...
M Austin Argentieri

Druggable genome screens identify SPP as an antiviral host target for multiple flaviviruses

6 months 3 weeks ago
Mosquito-borne flaviviruses, such as dengue virus (DENV), Zika virus (ZIKV), West Nile virus, and yellow fever virus, pose significant public health threats globally. Extensive efforts have led to the development of promising highly active compounds against DENV targeting viral non-structural protein 4B (NS4B) protein. However, due to the cocirculation of flaviviruses and to prepare for emerging flaviviruses, there is a need for more broadly acting antivirals. Host-directed therapy where one...
Wenjie Qiao

A galactose-tethered tetraphenylethene prodrug mediated apoptosis of senescent cells for osteoporosis treatment

6 months 3 weeks ago
Osteoporosis and bone injury healing in elderly patients are major medical challenges, often exacerbated by the accumulation of senescent cells. Herein, we show that TPE-Gal, which contains a tetraphenylethene unit and a galactose moiety, offers a promising molecular therapy designed to light up and eliminate senescent cells through a hydrolysis reaction catalyzed by β-galactosidase, an enzyme overexpressed in senescent cells. The reaction produces TPE-OH, which, in turn, increases reactive...
Xin Gao

Cortico-striatal action control inherent of opponent cognitive-motivational styles

6 months 3 weeks ago
Turning on cue or stopping at a red light requires attending to such cues to select action sequences, or suppress action, in accordance with learned cue-associated action rules. Cortico-striatal projections are an essential part of the brain's attention-motor interface. Glutamate-sensing microelectrode arrays were used to measure glutamate transients in the dorsomedial striatum (DMS) of male and female rats walking a treadmill and executing cued turns and stops. Prelimbic-DMS projections were...
Cassandra Avila

Large-Scale Clustered Transcriptional Silencing Associated With Cellular Senescence

6 months 3 weeks ago
Senescence is a cell fate associated with age-related pathologies; however, senescence markers are not well-defined. Using single cell multi-isotope imaging mass spectrometry (MIMS), we identified hypercondensed, transcriptionally silent DNA globules in a senescence model induced by dysfunctional telomeres. This architectural phenomenon was associated with geographically clustered transcriptional repression across somatic chromosomes with over-representation of cell cycle genes....
Aditi U Gurkar

Rejuvenating the gut: young plasma therapy improves cell proliferation, IGF-I and IGF-IR expression, and immune defense in aged male rats jejunum

6 months 3 weeks ago
It is well known that aging affects many systems in the body. The digestive system is one of the systems most affected by aging. In our study, we examined the effects of young plasma treatment on cell proliferation, growth factors, immune defense and histological parameters in the jejunum of aged male rats. For this purpose, aged male Sprague Dawley rats (24 months, n = 7) were treated with pooled plasma (0.5 ml/day, intravenously for 30 days) collected from young (5 weeks, n = 51) rats. Aged...
Ender Deniz Asmaz

Plasma homocysteine level and trajectories in association with longitudinal increase in plasma neurofilament light among urban adults

6 months 3 weeks ago
We tested whether homocysteine (Hcy) was linked to longitudinal change in plasma neurofilament light chain (NfL) overall and differentially across sex and race in a sample of middle-aged urban adults. We used data from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study [n = 690, Age at visit 1 (v(1):2004-2009): 30-66y, 42.1% male, 55.4% African American] to evaluate relationships between NfL levels and both visit 1 Hcy (Hcy(v1)) and time-dependent Hcy...
May A Beydoun