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Technology that uses a less known sensory system to substitute for olfaction could one day help anosmic people detect some odors

Parkinson's disease (PD) is an increasingly prevalent neurodegenerative disorder, largely sporadic in origin, with limited understanding of age- and region-specific lipid alterations in the human brain. Dysregulation of glycosphingolipid catabolism has been implicated in PD, yet comprehensive spatiotemporal profiling remains sparse. Here, we performed targeted lipidomics across eight anatomically distinct brain regions in post-mortem controls, mid-stage, and late-stage PD cases using...

Dementia is a defining feature of Lewy body disease: its timing and onset distinguish different clinical diagnoses, and its effect on quality of life is profound. However, it remains unclear whether processes leading to cognitive and motor symptoms in Lewy body disease differ. To clarify this, we use in-vivo neuroimaging to assess spatial gradients of inter-regional differences in structural and functional connectivity in 108 people across the Lewy body disease spectrum (46 Parkinson's with...

Aging impairs hematopoietic stem cells (HSCs), driving clonal hematopoiesis, myeloid malignancies, and immune decline. The role of lysosomes in HSC aging-beyond their passive mediation of autophagy-is unclear. We show that lysosomes in aged HSCs are hyperacidic, depleted, damaged, and aberrantly activated. Single-cell transcriptomics and functional analyses reveal that suppression of hyperactivated lysosomes using a vacuolar ATPase (v-ATPase) inhibitor restores lysosomal integrity and metabolic...

Previous reports revealed immune dysfunction, chromosomal abnormalities, cytokine deregulation, and telomere alterations after prolonged spaceflight. However, the stress of space on hematopoietic stem and progenitor cells (HSPCs) and the resilience properties maintaining lifelong hematopoiesis and immunity were not studied. We performed HSPC functionally organized multi-omics aging and resilience (HSPC-FOMA-R) analyses in 9 astronauts before, during, and after three short-duration International...

Translation is made of initiation, elongation, and termination. The role of termination in relaying extracellular outputs to the translation machinery is unknown. We show, in mice, that the controlled recycling of ribosomes post-termination is a major checkpoint that integrates mitogenic signals and antiviral responses. In detail, the recycling of ribosomes at stop codons, maximal translation, and cellular proliferation strictly depend on eIF6 phosphorylation, both in vitro and in vivo. Lack of...

Structural topology develops non-linearly across the lifespan and is strongly related to cognitive trajectories. We gathered diffusion imaging from datasets with a collective age range of zero to 90 years old (N = 4,216). We analyzed how 12 graph theory metrics of organization change with age and projected these data into manifold spaces using Uniform Manifold Projection and Approximation. With these manifolds, we identified four major topological turning points across the lifespan - around...

We investigate the effects of α-Klotho, an anti-aging hormone, on cell proliferation across three tissues with varying regenerative capacities in the context of aging. Using young and old wild-type mice, alongside old heterozygous Klotho-deficient mice, we administered soluble α-Klotho (sKL) daily for 10 weeks to elucidate the impact of α-Klotho deficiency and its supplementation. Our investigation spanned three organs: the small intestine, the kidney, and the heart. We measured cell cycle...

Senescence-associated frailty and sarcopenia are global challenges. We here investigated neuronal activity and skeletal muscle biology in senescence-accelerated mouse prone 8 (SAMP8) mice with scalp acupuncture stimulation (SAPS). Excise activity was assessed using rotarod test in the three groups: SAMP8 mice receiving SAPS (SP8-Ap), SAMP8 controls (SP8-C), and senescence-accelerated mouse resistant 1 controls (SR1). SP8-Ap exhibited significantly improved exercise activity compared to SP8-C....

Aneuploid cells are known to increase with age. Previously, we demonstrated an increased number of aneuploid fibroblasts isolated from aged mice due to chromosomal instability (CIN), which is caused by oxidative stress. It is unclear whether this phenomenon also occurs in human cells, which are more resistant to oxidative stress than mouse cells. Here, we found that fibroblasts from aged individuals exhibited an increase in aneuploid cells. The frequency of chromosome missegregation and...

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Intestinal stem cells (ISCs) drive the rapid regeneration of the gut epithelium. However, during aging, their regenerative capacity wanes, possibly through senescence and chronic inflammation, albeit little is known about how aging-associated dysfunction arises in the intestine. We previously identified the urokinase plasminogen activator receptor (uPAR) as a senescence-associated protein and developed CAR T cells able to efficiently target it. Harnessing them, here, we identify the accumulation...