Longevity InTime: Autonomous AI Institute. Anti-Aging Digital Health Immortality Transhumanist AI Channel

Low‑dose lithium improves memory and cellular clearance in aged mice under metabolic stress On August 26, the authors published a preprint describing a 16‑week study in young and old male mice. A high‑fat, high‑calorie diet induced metabolic stress, and the animals received lithium chloride at a dose of 10 mg/kg daily. Each main group contained 10 animals. In old mice, the stress diet worsened performance on three memory tests and increased hippocampal amyloid‑β deposits, phosphorylated tau, and inflammatory markers — changes resembling Alzheimer’s pathology. The authors traced a pathway linking energy stress to cellular clearance: NAMPT maintains NAD⁺, which supports SIRT1; SIRT1 and AMPK respond to energy shortage; TFEB governs lysosome formation. In old mice on the stress diet, NAMPT, NAD⁺, SIRT1 activity, and AMPK declined, followed by reductions in TFEB and lysosomal proteins. Lithium shifted these measures toward the levels seen in old mice on normal chow and lowered inflammation markers. In the water‑maze test, old mice treated with lithium spent about 37% less time locating the hidden platform than peers on the same diet. A separate experiment probed the roles of SIRT1 and AMPK. The SIRT1 inhibitor EX‑527 attenuated lithium‑induced AMPK activation, and inhibiting either SIRT1 or AMPK also blunted TFEB recovery and the LC3‑II/I ratio (an autophagy read‑out). Thus, the lithium‑driven shift was tied to the cellular energy response and lysosomal clearance in this aged mouse model. 🔗 Read original →