Don't View mTOR as a Single Pharmaceutical Target, as Context Matters

A new preprint study suggests that transplanted hearts’ epigenetic age and possibly function are influenced by their recipients’ age. The findings can be relevant to both expanding the donor pool and rejuvenation through organ replacement [1].

Later stages of Alzheimer's disease and other tauopathies are characterized by the aggregation of altered tau protein, and a toxic surrounding biochemistry that provokes inflammation and destroys neurons.

Researchers here provide an initial proof of concept demonstration of a novel foundation for replacing lost visual capacity in cases of retinal degeneration, without addressing the underlying pathology that causes loss of function in photoreceptor cells.

Iijima and colleagues identify a mechanism by which exercise promotes cartilage health through exercise-primed extracellular vesicles enriched in microRNA-29, which restore chondrocyte health and cartilage integrity through epigenetic derepression of KL.

Finger et al. report that declining synthesis of the mitochondrial membrane lipid cardiolipin is a feature of aging in mouse and human skeletal muscle, driving age-related fiber-type and metabolic adaptations through mitochondria-to-nucleus communication.

Extracellular α-synuclein activates the FLOT1-PI3K-mTOR axis to block autophagosome-lysosomal fusion and lipophagy, thereby promoting macrophage foaming and atherosclerosis. Knockdown of FLOT1 or inhibition of PI3K-mTOR rescues these effects. The graphical abstract image was created with Figdraw.

GFD-CD3, a uPAR-targeting T-cell engager, effectively cleared senescent cells and mitigated age-related pathologies with a favorable safety profile under transaminase-guided monitoring. Senolytic CAR-T cells targeting uPAR induce dose-dependent toxicities.

Cellular senescence and chronic low-grade inflammation occupy a central, mechanistically coupled position among the hallmarks of aging.