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Healthy Aging at Moderate Altitudes: Hypoxia and Hormesis

8 months 1 week ago
BACKGROUND: Aging is associated with cellular and tissue responses that collectively lead to functional and structural deterioration of tissues. Poor tissue oxygenation, or hypoxia, is involved in such responses and contributes to aging. Consequently, it could be speculated that living at higher altitude, and therefore in hypoxic conditions, accelerates aging. This assumption is indeed supported by evidence from populations residing at very high altitudes (>3,500 m). In contrast, accumulating...
Johannes Burtscher

Mild Behavioral Impairment and Quality of Life in Community Dwelling Older Adults

8 months 1 week ago
CONCLUSIONS: The study shows that MBI is associated with poorer QoL, independent of sex, on two QoL scales. We addressed depression/anxiety items in the EQ-5D as a potential confounder for the observed MBI-QoL association by conducting a sensitivity analysis that excluded those items from the EQ-5D total score and by employing a novel measure of QoL (QFS-5) that excludes psychiatric symptoms from measurement of QoL. Associations of MBI with the novel QFS-5 were similar to associations between...
Ibadat Warring

Prenatal exposure to undernutrition is associated with a specific lipid profile predicting future brain aging

8 months 1 week ago
Prenatal adversity affects cognitive and brain aging. Both lipid and leptin concentrations may be involved. We investigated if prenatal undernutrition is associated with a specific blood lipid profile and/or leptin concentrations, and if these relate to cognitive function and brain aging. 801 plasma samples of members of the Dutch famine birth cohort were assessed for lipidomics and leptin at age 58. Cognitive performance was measured with a Stroop task at 58, and MRI-based BrainAGE was derived...
Stuart G Snowden

Utilising an in silico model to predict outcomes in senescence-driven acute liver injury

8 months 1 week ago
Currently liver transplantation is the only treatment option for liver disease, but organ availability cannot meet patient demand. Alternative regenerative therapies, including cell transplantation, aim to modulate the injured microenvironment from inflammation and scarring towards regeneration. The complexity of the liver injury response makes it challenging to identify suitable therapeutic targets when relying on experimental approaches alone. Therefore, we adopted a combined in vivo-in silico...
Candice Ashmore-Harris

Therapeutic targeting of senescent cells in the CNS

8 months 1 week ago
Senescent cells accumulate throughout the body with advanced age, diseases and chronic conditions. They negatively impact health and function of multiple systems, including the central nervous system (CNS). Therapies that target senescent cells, broadly referred to as senotherapeutics, recently emerged as potentially important treatment strategies for the CNS. Promising therapeutic approaches involve clearing senescent cells by disarming their pro-survival pathways with 'senolytics'; or...
Markus Riessland

A biological age based on common clinical markers predicts health trajectory and mortality risk in dogs

8 months 1 week ago
Predicting aging trajectories through biomarkers of biological aging can guide interventions that optimize healthy lifespan in humans and companion animals. Differences in physiology, genetics, nutrition, and lifestyle limit the generalization of such biomarkers and may therefore require species-specific algorithms. Here, we compared correlations of standard clinical blood parameters with survival probability in humans with those of the two most common mammalian companion animals, cats and dogs,...
Sébastien Herzig

p21 regulates expression of ECM components and promotes pulmonary fibrosis via CDK4 and Rb

8 months 1 week ago
Fibrosis and accumulation of senescent cells are common tissue changes associated with aging. Here, we show that the CDK inhibitor p21 (CDKN1A), known to regulate the cell cycle and the viability of senescent cells, also controls the expression of extracellular matrix (ECM) components in senescent and proliferating cells of the fibrotic lung, in a manner dependent on CDK4 and Rb phosphorylation. p21 knockout protects mice from the induction of lung fibrosis. Moreover, inducible p21 silencing...
Nurit Papismadov

Insulin-inspired hippocampal neuron-targeting technology for protein drug delivery

8 months 1 week ago
Hippocampal neurons can be the first to be impaired with neurodegenerative disorders, including Alzheimer's disease (AD). Most drug candidates for causal therapy of AD cannot either enter the brain or accumulate around hippocampal neurons. Here, we genetically engineered insulin-fusion proteins, called hippocampal neuron-targeting (Ht) proteins, for targeting protein drugs to hippocampal neurons because insulin tends to accumulate in the neuronal cell layers of the hippocampus. In vitro...
Noriyasu Kamei