Energy metabolism dysregulation, cerebrovascular aging, and time-restricted eating: Current evidence and proof-of-concept findings

Abstract

Dysregulated energy metabolism is a hallmark of aging, including brain aging; thus, strategies to restore normal metabolic regulation are at the forefront of aging research. Intermittent fasting, particularly time-restricted eating (TRE), is one of these strategies. Despite its well-established effectiveness in improving metabolic outcomes in older adults, the effect of TRE on preserving or improving cerebrovascular health during aging remains underexplored. We explored how aging itself affects energy metabolism and contextualized these age-related changes to cerebrovascular health. We also conducted a literature search on PubMed and Scopus to identify and summarize current studies on TRE in older adults. Finally, we provided preliminary data from our proof-of-concept pilot trial on the effect of 6-month TRE on cerebrovascular health in older adults. Current evidence shows the potential of TRE to improve energy metabolism and physiological outcomes in older adults. TRE may improve cerebrovascular function indirectly due to its effect on glucose homeostasis. However, to date, direct evidence of the effect of TRE on cerebrovascular parameters is lacking. TRE is a well-tolerated and promising dietary intervention for promoting and maintaining cerebrovascular health in older adults. Further studies on TRE in older adults must be better controlled for energy balance to elucidate its independent effects from those of caloric restriction.

Keywords: cerebrovasculature; dietary intervention; energy metabolism; intermittent fasting; older adults.

Fig. 1.

Schematic representation of how age-related energy metabolism dysregulation can initiate and propagate signaling cascades associated with cerebrovascular aging in endothelial cells. AGE, advanced glycation end products; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; MMP, matrix metalloproteinase; mTOR, mammalian target of rapamycin; NAD, nicotinamide adenine dinucleotide; NF-κB, nuclear factor kappa B. Created with BioRender.com.

Fig. 2.

Effect of a 6-month 14:10 TRE regimen in older women on NVC responses assessed using functional near-infrared spectroscopy. The heatmap illustrates the distribution of oxygenated hemoglobin in cortical tissues during a working memory paradigm (N-back task), comparing responses before and after TRE intervention in six participants (mean age: 60.2 ± 3.9 years). Red and blue shaded areas indicate statistically significant increases and decreases, respectively, in NVC during the performance of more (2-back) vs. less challenging (1-back) tasks. More cognitively demanding tasks are expected to increase oxygenated hemoglobin concentrations at a greater magnitude compared with less cognitively demanding tasks.