Volume 4 Issue 4, April 2024

Xu and colleagues used partial OSKM reprogramming in aged mice to drive cell-type proportions of the subventricular zone to more youthful levels, which equates to qualified rejuvenation of a neurogenic niche that is defined, in part, by restoration of neuroblast levels.

Epidemiological studies reveal a correlation between hearing loss and the development and progression of Alzheimer’s disease (AD), but the underlying causal mechanisms remain unclear. A study now provides experimental evidence that hearing loss can promote AD via the growth differentiation factor 1 (GDF1) pathway, which may aid in developing potential AD therapeutic strategies.

On 29–30 November 2023, the inaugural Global Healthspan Summit, convened in Riyadh by the nonprofit Hevolution Foundation, provided a dynamic platform that united experts from diverse sectors to foster collaborative discussions on aging research, innovative healthcare strategies and the healthspan ecosystem. This Meeting Report encapsulates the multifaceted insights that were garnered from the perspectives of science, economics and society.

Intensive blood pressure control has been suggested to reduce the risk of adverse cardiovascular events. However, the effect of intensive blood pressure control on cardiac conduction system disease has not been clarified. Our study in older patients with hypertension identified no effect of intensive blood pressure control on cardiac conduction system diseases.

Our analysis of the spatiotemporal transcriptional features of human ovarian aging at the single-cell level identified the DNA damage response as a fundamental attribute in oocyte senescence. FOXP1, a gatekeeper both in granulosa and in theca and stroma cellular senescence, can be activated by quercetin treatment to delay ovarian aging.

The advent of plaque-clearing antibodies to the amyloid-β as the first disease-modifying treatment for Alzheimer’s disease will change the course of this disease, the most common type of dementia. Related progress will gradually alter the trajectory of human aging.

Wu et al. explore vaccine strategies targeting age-related diseases, as well as senescent cells specifically, as potential underlying drivers of aging itself. They discuss challenges faced in clinical trials, as well as further optimizations required to increase therapeutic efficacy.

Zhao, Deng and colleagues present a post hoc analysis of the STEP trial showing that intensive blood pressure control does not reduce the risk of cardiac conduction diseases in older adults with hypertension.

Zhang et al. demonstrate that S6K suppression in the Drosophila fat body mediates the longevity effects of rapamycin and identify Syntaxin 13 as a conserved downstream effector regulating lysosome morphology and inflammation in a sex-specific manner.

He et al. characterizes a role of microcephalin (MCPH1), a known regulator of DNA damage response, in hematopoietic stem cell (HSC) aging demonstrating nuclear MCPH1 translocation that leads to activation of necroptosis and deterioration of HSC function with age.

Ovarian aging has an important role in health and fertility; however, the molecular mechanisms underlying it remain incompletely understood. Here the authors use single-cell and spatial transcriptomics in reproductively young, middle-aged and older human ovarian tissue to elucidate ovarian aging. They describe spatiotemporal changes in ovarian cells and highlight the important regulatory role of FOXP1.

Xu et al. use single-cell transcriptomics to reveal that targeted and systemic partial reprogramming restore the production of neuronal progenitors and new neurons in old mice and show a cell-autonomous effect of reprogramming in cultures of aged neural stem cells.

Pan et al. demonstrate that hearing loss promotes cognitive decline in an APP/PS1 mouse model of Alzheimer disease via inhibition of the GDF1 signaling pathway, unveiling GDF1 as a therapeutic target for Alzheimer disease.

In a longitudinal population-based cohort, Liu et al. demonstrate that integrating polygenic risk scores and the gut microbiome improved prediction, over traditional risk factors, for heart disease, diabetes, Alzheimer disease and prostate cancer.

Todorov-Völgyi, González-Gallego et al. provide a proteomic profiling of brain endothelium during aging to unveil changes undetected in transcriptomic studies, identifying a dysregulation of proteins involved in vesicle-mediated transport pathways, most prominently Arf6.