Time-restricted feeding rejuvenates cerebrovascular function and preserves cognition during aging

Area of Science:

• Neuroscience
• Gerontology
• Metabolic research

Background:

• Cerebromicrovascular dysfunction significantly contributes to age-related cognitive decline.
• Current interventions for microvascular aging are limited, necessitating novel therapeutic strategies.

Purpose of the Study:

• To investigate the effects of time-restricted feeding (TRF) on cognitive function and cerebrovascular health in aged mice.
• To elucidate the underlying mechanisms by which TRF impacts brain aging.

Main Methods:

• Aged mice were subjected to time-restricted feeding (TRF).
• Cognitive function, cerebral blood flow, neurovascular coupling, blood-brain barrier integrity, neuroinflammation, and endothelial senescence were assessed.
• Mitochondrial function and metabolic flexibility in cerebromicrovascular endothelial cells were analyzed.
• The effects of ketone bodies were evaluated in vivo and in vitro.

Main Results:

• TRF preserved cognitive function and rejuvenated cerebrovascular physiology in aged mice.
• TRF improved cerebral blood flow and neurovascular coupling, while reducing blood-brain barrier disruption, neuroinflammation, and endothelial senescence.
• Mechanistically, TRF enhanced metabolic flexibility and restored mitochondrial bioenergetic capacity.
• Elevated ketone bodies mimicked some mitochondrial and vascular effects of TRF but did not fully protect the neurovascular unit.

Conclusions:

• Endothelial mitochondrial reprogramming is a key mechanism linking dietary timing to cerebrovascular resilience and cognitive preservation.
• Metabolic interventions like TRF show potential for partially reversing key features of vascular brain aging.
• TRF offers a promising strategy for mitigating age-related cognitive decline through improved cerebrovascular health.