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Toren Finkel reviews how metabolism and aging are connected, and highlights pathways that could be pharmacologically targeted to combat aging and age-related disease.
In this Perspective, the mechanisms by which proteostasis is coordinated within and between cells is discussed with an emphasis on how these mechanisms are deregulated upon aging.
In this Review, Jan van Deursen and his colleagues discuss the recent progress in understanding the origin and identity of senescent cells in ageing and their contribution to age-related disease, in addition to discussing the potential for targeting these cells to counteract disease.
The details of the GIP signaling pathway are murky, but new data identify a downstream pathway involving Tcf7 that regulates beta cell survival and activity.
Mutations in VPS35 that are associated with Parkinson's disease increase the interaction of VPS35 with mitochondrial DLP1, leading to removal of the DLP1 complexes and mitochondrial fragmentation. Structural and functional mitochondrial impairments caused by mutant VPS35 are observed in vitro using cultured neurons and fibroblasts from individuals with PD and in vivo in mouse substantia nigra neurons, where they induce neurodegeneration.
The authors analyze the extent of intratumor heterogeneity across 12 tumor types to reveal that increased heterogeneity is a general phenomenon and has a biphasic contribution to tumor progression.
Treatment with the common diuretic bumetanide during a susceptible developmental window prevents epileptogenesis in a mouse model of a genetic epileptic encephalopathy.
The authors uncover a therapeutic vulnerability to PARP inhibition of acute myeloid leukemias driven by certain oncogenic fusions, and they unravel the mechanisms by which these cancers rely on DNA damage and repair pathways for growth.
An inhibitor of Aurora kinase promotes megakaryocytic differentiation of cells from patients with primary myelofibrosis and shows antifibrotic effects in mouse models of this disease.
Ralph Baric, Vineet Menachery and colleagues characterize a SARS-like coronavirus circulating in Chinese horseshoe bats to determine its potential to infect primary human airway epithelial cells, cause disease in mice and respond to available therapeutics.
The authors identify EZH2 as a general underlying dependency of tumors with mutations in the SWI/SNF chromatin regulator complex, and they show that EZH2's pro-tumorigenic role may be dependent on non-catalytic activities. This may pose new opportunities and challenges for using EZH2 as a cancer therapy target.
Journals can and should ensure that they erect no barriers to fast and wide sharing of critical data during major public health emergencies. But funders and scientists must also play a part.
Neutralization breadth is thought to be an important feature of an effective vaccine against HIV-1. A study in one individual has now identified the specific viral variant that engaged the necessary antibody precursor, as well as the viral immunotypes that drove neutralization breadth, improving understanding of how to mimic this process with a vaccine.