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DNA damage promotes mutations that fuel cancer, ageing and neurodegenerative diseases^(1-3), but surprisingly, the causes and types of damage remain largely unknown. There are three identified mechanisms that damage DNA during transcription: collision of RNA polymerase (RNAP) with the DNA-replication machinery head-on and co-directionally^(4-6), and R-loop-induced DNA breakage^(7-10). Here we identify novel DNA damage reaction intermediates^(11,12) and uncover a fourth transcription-related...

Consequences of age-associated thymic atrophy include declining T-cell responsiveness to pathogens and vaccines and diminished T-cell self-tolerance. Cortical thymic epithelial cells (cTECs) are primary targets of thymic aging, and recent studies suggested that their maintenance requires mTOR signaling downstream of medullary TEC (mTEC)-derived growth factors. Here, to test this hypothesis, we generated a knock-in mouse model in which FGF21 and mCherry are expressed by most mTECs. We find that...

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...

CONCLUSIONS: Education plays a crucial role in enabling females to overcome disadvantages associated with the gender paradox in China. Enhancing gender equality in educational opportunities is expected to promote healthy longevity among females in the country.

CONCLUSIONS: Elevated NLR status is associated with increased risk of cognitive impairment in Chinese community-dwelling older adults.

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...

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...

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...

New material that could be spread on fields locks up CO2 in minerals

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....

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...

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...

CONCLUSION: Gamma-band ASSR characteristics are linked to early cognitive decline in middle-aged individuals, offering potential as biomarkers. However, the limited predictive accuracy of ML models emphasizes the need for further refinement to enhance their clinical applicability.