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Aging is characterized by the accumulation of proteins that display amyloid-like behavior. However, the molecular mechanisms by which these proteins arise remain unclear. Here, we demonstrate that amyloid-like proteins are produced in a variety of human cell types, including stem cells, brain organoids and fully differentiated neurons by mistakes that occur in messenger RNA molecules. Some of these mistakes generate mutant proteins already known to cause disease, while others generate proteins...

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Preservation of brain health is a worldwide priority. The traditional view is that the major threats to the ageing brain lie within the brain itself. Consequently, therapeutic approaches have focused on protecting the brain from these presumably intrinsic pathogenic processes. However, an increasing body of evidence has unveiled a previously under-recognized contribution of peripheral organs to brain dysfunction and damage. Thus, in addition to the well-known impact of diseases of the heart and...

Over the course of the twentieth century, human life expectancy at birth rose in high-income nations by approximately 30 years, largely driven by advances in public health and medicine. Mortality reduction was observed initially at an early age and continued into middle and older ages. However, it was unclear whether this phenomenon and the resulting accelerated rise in life expectancy would continue into the twenty-first century. Here using demographic survivorship metrics from national vital...

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Cellular senescence is an established cause of cell and tissue aging. Senescent cells have been shown to increase in multiple organs during aging, including the skin. Here we hypothesized that senescent cells residing in the skin can spread senescence to distant organs, thereby accelerating systemic aging processes. To explore this hypothesis, we initially observed an increase in several markers of senescence in the skin of aging mice. Subsequently, we conducted experiments wherein senescent...

The disposable soma theory (DST) posits that organisms age and die because of a direct trade-off in resource allocation between reproduction and somatic maintenance. DST predicts that investments in reproduction accentuate somatic damage which increase senescence and shortens lifespan. Here, we directly tested DST predictions in breeding and nonbreeding female C57BL/6J mice. We measured reproductive outputs, body composition, daily energy expenditure, and oxidative stress at peak lactation and...

Single-cell RNA sequencing and spatial transcriptomics enable unprecedented insight into cellular and molecular pathways implicated in human skin aging and regeneration. Senescent cells are individual cells that are irreversibly cell cycle arrested and can accumulate across the human lifespan due to cell-intrinsic and -extrinsic stressors. With an atlas of single-cell RNA-sequencing and spatial transcriptomics, epidermal and dermal senescence and its effects were investigated, with a focus on...

The integrity of the actively transcribed genome against helix-distorting DNA lesions relies on a multilayered cellular response that enhances Transcription-Coupled Nucleotide Excision Repair (TC-NER). When defective, TC-NER is causatively associated with Cockayne-Syndrome (CS), a rare severe human progeroid disorder. Although the presence of unresolved transcription-blocking lesions is considered a driver of the aging process, the molecular features of the transcription-driven response to...

Extracellular vesicles (EVs) are nanosized particles that are released by various cell types and play vital roles in intercellular communication. They carry biological molecules reflecting the physiological and pathological states of their source cells and tissues, showing potential as biomarkers. However, the impact of demographic factors like age and sex on the properties of blood plasma EVs remains underexplored. This study aims to fill this gap by evaluating how these factors influence the...

CONCLUSIONS: Our study reveals that the use of lipophilic statins is significantly associated with lower all-cause and cancer-cause mortality risks among aging cancer survivors.