Volume 4 Issue 7, July 2024

A study demonstrates the efficacy of immune-checkpoint blockade in prolonging survival and boosting CD8⁺ T cell function in aged mice after pathogen exposure. These findings highlight how aging-related immune changes may lead to augmented CD8⁺ T cell responses to checkpoint blockade, which results in improved protection from infection. The findings also highlight the importance of understanding immune aging in future efforts to target immunotherapies to older adults.

Inhibitors of sodium glucose co-transporter 2 (SGLT2) have long been used in the treatment of diabetes and cardiovascular disease, owing to their modulation of glucose levels. Katsuumi and colleagues now show that, in addition to their glycemic effects, SGLT2 inhibitors modulate senescence immune surveillance by downregulating PD-L1 expression on senescent cells.

Older age is associated with metabolic stress and increases the risk of degeneration of organs that maintain metabolic homeostasis, including the liver. We discovered that aging promotes ferroptosis in hepatocytes, that ferroptotic stress is generally increased in degenerating organs, and that reducing ferroptosis reverses aging-related metabolic dysfunction and liver damage.

A deep learning model accurately predicts 1-year mortality for the entire Finnish population. Despite robust performance and potential as a digital marker of aging, fairness analyses reveal prediction disparities, so integration into public health should be approached cautiously.

This study shows that normal microbial exposure increases inflammation and CD8⁺ T cell exhaustion and leads to mortality in old mice; it also shows that anti-PD1 antibody treatment restores survival and increases CD8⁺ cytotoxic capacity, without altering inflammation.

Katsuumi, Shimizu, Suda et al. report that SGLT2 inhibition reduces the senescence burden and alleviates aging traits in mice. The authors demonstrate an indirect mechanism of senescent cell removal, through enhancing immunosurveillance.

Gadd et al. identify proteins circulating in the blood that can stratify the risk people have of developing a range of leading age-related diseases, up to a decade before onset.

The mechanisms underlying susceptibility to metabolic dysfunction-associated steatotic liver disease (MASLD) in aging are incompletely understood. Here the authors show that an aging hepatocyte gene signature is enriched in MASLD liver tissue and contains ferroptosis genes. Experiments in mice show that metabolic stress increases ferroptosis in liver tissue in old compared to young animals and that blocking ferroptosis in old animals reduces the susceptibility to metabolic stress.

Inclusion body myositis (IBM) is a progressive inflammatory muscle disease of unknown cause, prevalent in older adults. Through spatial and single nuclear profiling, the authors identify a selective type 2 myofiber pathology in IBM, linked to genomic stress and denervation.

Using single-nucleus RNA sequencing data from patients with sporadic amyotrophic lateral sclerosis (ALS) cortices, the authors find that higher expression of ALS risk genes is accompanied by upregulation of stress responses in groups of extratelencephalic neurons. Analyses of glial nuclei revealed a downregulation of myelination genes in oligodendrocytes and upregulation of reactive state genes in microglia.

This comprehensive resource offers new insights into how different types of cell and tissue change with age in C. elegans and unveils the distinctive anti-aging effects of various pro-longevity strategies in a cell-type-specific manner.

Here the authors show that deep learning accurately predicts one-year mortality using nationwide Finnish data. Despite robust performance and potential as an aging marker, fairness analyses reveal prediction disparities, urging cautious integration into public health.