Scientists find a key to delay brain ageing

For centuries humans have been keen on reversing age. Especially the

cognitive decline

that is linked to aging. Aging is associated with impairments in mitochondrial functions. However, scientists have now found a crucial key that would help to combat age-related cognitive decline. In a new research in mice, the scientists have found a crucial mechanism linking

neuronal activity

to

mitochondrial function

and also unveiled a potential pathway to combat cognitive decline.
Mitochondria plays a crucial role in meeting the dynamic energy demands of neuronal activity, producing adenosine triphosphate (ATP) primarily via oxidative phosphorylation (OXPHOS). But in the mammalian brain, aging comes with mitochondrial metabolism deterioration, which affects the neuronal and circuit functionality. The disruption of the OXPHOS pathway results in oxidative stress and mitochondrial dysfunction. Despite its crucial role, there was little understanding of the mechanisms underlying the decline in OXPHOS activity and its impact on mitochondrial efficiency in aging neurons. This gap in understanding posed a major challenge to developing targeted interventions for mitigating age-related cognitive decline.

Wenwen Li and colleagues started to investigate the role of mitochondrial transcription in cognition in the hippocampus of young and aged mice. Li et al. found a novel coupling mechanism, which they dubbed excitation-mitochondrial DNA transcription coupling (E-TCmito), that connects neuronal excitation with mitochondrial DNA transcription. This coupling was different from the traditional excitation-transcription coupling in the nucleus. They found out that

E-TCmito

plays a critical role in maintaining both synaptic and mitochondrial health, and its significance in neuronal function and overall cellular energy homeostasis. In aging brains, E-TCmito becomes less effective, contributing to cognitive decline. The scientists noticed that boosting E-TCmito in aged mice improved their cognitive function, and it could be a promising target for therapies to combat age-related cognitive decline.

“Through an impressive combination of innovative tools, innovative physiology, and behavior experiments, Li et al. provide key insights into mitochondrial biology in the aging mammalian brain,” the authors Deniz Bingul and Scott Owen wrote in a related Perspective.
They added, “The findings raise the possibility of identifying targets for age-related neurocognitive disorders associated with mitochondrial dysfunction, including Alzheimer’s and Parkinson’s diseases.”

The study, Boosting neuronal activity-driven mitochondrial DNA transcription improves cognition in aged mice, is published in the Science Journal.