One of the things that can be done with an aging clock based on transcriptomics is to screen compound libraries for drug candidates that reduce age-related changes in gene expression in specific cell populations. Here, researchers run an in vitro screen for compounds capable of achieving this goal in various brain cell types. It is likely that this sort of work will over time greatly expand the present list of compounds known to at modestly slow aging, but it seems unlikely to make more more of a difference than that. Based on past results, any sort of unbiased screening will uncover novel calorie restriction mimetics and senotherapeutics with modest effect sizes. There doesn't appear to be much else under this stone; researchers announce rejuvenation, but one always has to look at the effect sizes, which are usually small. More impressive interventions in aging seem likely to only emerge from the deliberative design of more advanced forms of drug capable of achieving specific goals related to the damage and dysfunction of aging.
The increase in life expectancy has caused a rise in age-related brain disorders. Although brain rejuvenation is a promising strategy to counteract brain functional decline, systematic discovery methods for efficient interventions are lacking. A computational platform based on a transcriptional brain aging clock capable of detecting age- and neurodegeneration-related changes is developed. Applied to neurodegeneration-positive samples, it reveals that neurodegenerative disease presence and severity significantly increase predicted age.
By screening 43,840 transcriptional profiles of chemical and genetic perturbations, it identifies 453 unique rejuvenating interventions, several of which are known to extend lifespan in animal models. Additionally, the identified interventions include drugs already used to treat neurological disorders, Alzheimer's disease among them. A combination of compounds predicted by the platform reduced anxiety, improved memory, and rejuvenated the brain cortex transcriptome in aged mice. These results demonstrate the platform's ability to identify brain-rejuvenating interventions, offering potential treatments for neurodegenerative diseases.
Link: https://doi.org/10.1002/advs.202503344
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