Volume 4 Issue 5, May 2024

Zou and colleagues design and analyze a health education program that targeted college students (who were grandchildren) to encourage older persons who had already had their first COVID-19 vaccine dose to receive a booster. The program increased the uptake of booster doses, which highlights the fact that family ties can have positive roles in the context of a pandemic.

Zhou and colleagues explore reversing testicular aging and late-onset hypogonadism by targeting lysosomal function in Sertoli cells. The aging-related transformation of Sertoli cells into a lipid-hoarding subtype with dysregulated phagolysosomes and autolysosomes was reversed using the TRPML channel agonist ML-SA1, which demonstrates the potential of this targeted therapy in alleviating testosterone decline and systemic male-aging phenotypes.

Skeletal muscle is a highly heterogenous tissue that comprises multiple cell types. Leveraging single-cell and single-nucleus experiments, we systematically mapped the cellular and molecular changes across different skeletal muscle compartments with age. We identify neuromuscular-junction accessory nuclei that may be pivotal in mitigating denervation and uncovered differences between myofiber and myonucleus aging.

Staging Alzheimer’s disease on the basis of the disease’s biological underpinnings might help with stratification and prognostication, both in the clinical setting and in clinical trials. We propose a staging model based on only five biomarkers, which are related to amyloid-β and tau pathologies in different ways and can be measured with a single sample of cerebrospinal fluid.

In vivo human neuroimaging shows that locus coeruleus (LC) integrity changes precede medial temporal tau accumulation, and jointly predict future lower cognition in older people at risk for Alzheimer’s disease. A common transcriptomic profile underlies LC’s early vulnerability to tau.

Bian, Zhang, Guo, Li, Fu et al. present results of a parallel-group, cluster-randomized controlled trial demonstrating the efficacy of an educational intervention targeting college students in increasing COVID-19 booster vaccination uptake among grandparents in China.

Late-onset hypogonadism (LOH) can occur with male reproductive aging and is characterized by declining testosterone levels as well as other clinical symptoms. Here the authors show that dysregulated phago-/auto-lysosomes in Sertoli cells are a key feature of LOH, linking metabolism and aging, and that pharmaceutical targeting of lysosome dysfunction can alleviate LOH in mice.

Liu et al. identify downregulation of DDX5, an RNA helicase, in the cartilage of patients and mouse model of osteoarthritis. Targeted upregulation of DDX5 in mouse chondrocytes inhibits hyaline cartilage fibrosis and degradation via pre-mRNA splicing and G4 unwinding, a potential therapeutic strategy against osteoarthritis.

Aging dynamics of complex lipids are incompletely understood. Here Janssens and colleagues describe lipids that change with age across ten tissues in mice. Notably, bis(monoacylglycerol)phosphate accumulated with age. This lipid also accumulated in muscle of older humans, and reduced upon a short bout of exercise.

Salvadó et al. developed and validated a CSF-based staging model for sporadic Alzheimer’s disease, which accurately reflects biomarker and clinical changes, enhancing diagnostic and prognostic assessments of participants for clinical setting and trials.

Lipid changes across the lifespan and their role in health and longevity are incompletely understood. Here, Tsugawa and colleagues conduct untargeted lipidomics across 13 sample types and four ages in mice, considering sex and microbiome dependencies. This study provides a comprehensive resource of lipid changes with aging and highlights regulatory metabolic components, such as the enzyme UGT8, as potentially responsible for male-specific glycolipid biosynthesis in the kidney.

The Muscle Aging Cell Atlas presents approximately 200,000 single-cell and single-nuclei transcriptomes from 17 human donors across different ages, uncovering mechanisms of aging in muscle stem cells, myofibers and microenvironment cells, and demonstrates parallels in mouse muscle aging.