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Hematopoietic stem cells (HSCs) with mutations that can cause clonal hematopoiesis of indeterminate potential (CHIP) accumulate during aging. Agarwal et al.¹ demonstrate in Nature that intestinal barrier permeability increases with age and enables the microbial metabolite ADP-heptose to reach the bone marrow, thus driving the expansion of DNMT3A-mutant HSCs.

Epigenome-wide association studies (EWASs) are transforming our understanding of the interplay between epigenetics and complex human traits. We introduce the methylation screening array (MSA) to enable scalable and quantitative screening of trait-associated DNA cytosine modifications in large human populations. The MSA integrates EWASs and cell-type-linked methylation signatures, covering diverse traits and diseases. Using the MSA to profile the ternary-code DNA methylations-dissecting...

Disseminated tumor cells (DTCs) can remain in a non-proliferative, dormant state for years in distant organs, but the exogenous causes triggering their reactivation and metastatic colonization are unclear. Here, we demonstrate that chemotherapeutic drugs, including doxorubicin and cisplatin, enhance proliferation and lung metastasis of dormant breast cancer cells. Using a recombinase-based dormancy tracing system, DormTracer, we confirm chemotherapy-induced reactivation of dormant DTCs leading...

BRAF and MEK inhibitors (BRAF/MEKi) have radically changed the treatment landscape of advanced BRAF mutation-positive tumours. However, limited efficacy and emergence of drug resistance are major barriers for successful treatments. Here, by using relevant preclinical models, we find that Connexin43 (Cx43), a protein that plays a role in cell-to-cell communication, enhances the effectiveness of BRAF/MEKi by recruiting DNA repair complexes to lamin-associated domains and promoting persistent DNA...

Taurine is a conditionally essential nutrient and one of the most abundant amino acids in humans, with diverse physiological functions. The cellular uptake of taurine is primarily mediated by the taurine transporter (TauT), and its dysfunction leads to retinal regeneration, cardiomyopathy, neurological and aging-associated disorders. Here we determine structures of TauT in two states: the apo inward-facing open state and the occluded state bound with substrate taurine or γ-aminobutyric acid...

Mobility is a cornerstone of health and quality of life, particularly in older adults. Digital mobility outcomes (DMOs) from real-world walking data offer crucial insights into the functional status and early markers of mobility decline. This study provides reference values for walking activity, pace, rhythm, and gait bout-to-bout variability in community-dwelling older adults and evaluates the effects of age, sex, height, and weight on these parameters. Using data from 200 older adults (aged...

We constructed a polygenic protective score specific to Alzheimer's disease (AD PPS) based on the current literature among the participants enrolled in five studies of healthy aging and extreme longevity in the USA, Europe, and Asia. This AD PPS did not include variants on apolipoprotein E (APOE) gene. Comparisons of AD PPS in different data sets of healthy agers and centenarians showed that centenarians have stronger genetic protection against AD compared to individuals without familial...

One of the prokaryotic partners at the origin of eukaryotes was an archaeon, but do archaea age, and if so, how? Uncovering aging in Archaea might provide more general clues about cellular senescence and rejuvenation and their origins. To fill this knowledge gap, we focused on Saccharolobus islandicus, a model archaeon for which the cell cycle can be synchronized and controlled. We generated longitudinal transcriptomes of synchronized S. islandicus populations that capture typical expression and...

While the etiology of Alzheimer's disease remains unknown, there is growing support for the amyloid-β antimicrobial hypothesis. Amyloid-β, the main component of amyloid plaques in Alzheimer's disease, has been shown to be generated in the presence of microbes. Entrapment of microbes by aggregated amyloid-β may serve as an innate immune response to pathogenic infections. To understand the association of amyloid-β plaques and pathogenic infections in the central nervous system, we obtained viable...

A gel that bats lick off one another’s fur could help prevent rabies outbreaks in cattle, a growing problem in Latin America

CONCLUSIONS: The sexual program which handled comprehensive and interdisciplinary approach could offer more than just addressing sexual function. Due to the unreached significant increase in sexual esteem and sexual quality of life and lack of knowledge about these, there is a need to have future studies. It is essential for national health policies to incorporate and act on interdisciplinary approach to sexuality in older adults.

CONCLUSION: Maintaining an appropriate level of overweight or even a state of obesity can contribute to the preservation of cognitive health in older adults. This factor holds significant importance as it is a preventive measure against the onset of cognitive impairment.