SciFocus/Dec 24, 2024 — The study reveals that enhancing mitochondrial transcription in neurons sustains energy reserves and synaptic resilience, offering a new target to counteract cognitive aging.
Aging and Cognition: The Mitochondrial Connection
Aging brings a decline in mitochondrial function, impacting energy production and cognitive health. Researchers led by Li et al., in a groundbreaking study published in Science, have demonstrated how enhancing mitochondrial DNA transcription in neurons can mitigate age-related cognitive decline.
“This findings show that targeting mitochondrial transcription processes may offer a promising therapeutic avenue for combating age-related memory loss.”
Key Highlights
- Activity-Driven Mitochondrial Gene Expression:
Neuronal and synaptic activity enhances mitochondrial DNA transcription through calcium signaling and specific protein interactions. - Mechanisms Identified:
- Mitochondrial calcium influx ([Ca²⁺]mito) is pivotal.
- Key regulators include mitochondrial calcium uniporter (MCU), CaMKIImito, and CREBmito.
- Impact on Aging:
Aged mice showed reduced activity-driven mitochondrial transcription and compromised energy reserves. - Therapeutic Intervention:
Expressing a constitutively active CREBmito in aged mice restored transcription, improved energy metabolism, and significantly enhanced memory performance. - Implications:
- Highlights a novel coupling between neuronal activity and mitochondrial function.
- Suggests potential treatments for age-related cognitive decline and neurodegenerative disorders.
Reference
Li et al. “Boosting neuronal activity-driven mitochondrial DNA transcription improves cognition in aged mice.” Science, Vol 386, Issue 6728, 20 Dec 2024. DOI: 10.1126/science.adp6547.
