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Three monoclonal antibodies directed against specific forms of the amyloid-β (Aβ) peptide have been granted accelerated or traditional approval by the FDA as treatments for Alzheimer disease, representing the first step towards bringing disease-modifying treatments for this disease into clinical practice. Here, we review the detection, underlying pathophysiological mechanisms and clinical implications of amyloid-related imaging abnormalities (ARIA), the most impactful adverse effect of anti-Aβ...

In single cells, variably sized nanoscale chromatin structures are observed, but it is unknown whether these form a cohesive framework that regulates RNA transcription. Here, we demonstrate that the human genome is an emergent, self-assembling, reinforcement learning system. Conformationally defined heterogeneous, nanoscopic packing domains form by the interplay of transcription, nucleosome remodeling, and loop extrusion. We show that packing domains are not topologically associated domains....

The proteasome degrades most superfluous and damaged proteins, and its decline is associated with many diseases. As the proteolytic unit, the 20S proteasome is assembled from 28 subunits assisted by chaperones PAC1/2/3/4 and POMP; then, it undergoes the maturation process, in which the proteolytic sites are activated and the assembly chaperones are cleared. However, mechanisms governing the maturation remain elusive. Here, we captured endogenous maturation intermediates of human 20S proteasome,...

C-Terminal cyclic imides are posttranslational modifications that can arise from spontaneous intramolecular cleavage of asparagine or glutamine residues resulting in a form of irreversible protein damage. These protein damage events are recognized and removed by the E3 ligase substrate adapter cereblon (CRBN), indicating that these aging-related modifications may require cellular quality control mechanisms to prevent deleterious effects. However, the factors that determine protein or peptide...

OBJECTIVES: To examine the association of social connections with blood leukocyte telomere length (LTL) and all-cause mortality in older Costa Ricans.

The decline of oocyte quality with advanced maternal age has a detrimental effect on female fertility. However, there is limited knowledge of therapeutic options and their mechanisms to improve oocyte quality in reproductively older women. In this study, we demonstrated that supplementation of salidroside improves the oocyte quality of reproductively old mice. Salidroside improved the maturation, fertilization, and developmental competence of oocytes from reproductively old mice by maintaining...

The current mechanism by which aging reduces salivary secretion is unknown. This study investigates the mechanism of aging-related submandibular (SMG) dysfunction and evaluates the therapeutic potential of dental pulp stem cell-derived exosomes (DPSC-exos). We found that the stimulated salivary flow rate was significantly reduced in naturally aging and D-galactose-induced aging mice (D-gal mice) compared to control mice. Acinar atrophy and periductal fibrosis in SMGs and parotid glands (PGs)...

Science, Volume 387, Issue 6730, January 2025.

Science, Volume 387, Issue 6730, January 2025.

Science, Volume 387, Issue 6730, January 2025.