Supplementing NMN to Combat Aging-Related Blood-Brain Barrier

 

In September 2023, a study published in the journal Neuron found that supplementing NMN (the precursor of NAD+) can promote the CX43-PARP1-NAD+ pathway to protect the blood-brain barrier function during aging.

Blood-brain barrier function deteriorates with age, leading to cognitive impairment and neurodegeneration. It's unclear what causes the blood-brain barrier to leak during aging and how to prevent it. Therefore, the article revolves around this issue.

Using single-nucleus transcriptomics, reduced connexin 43 (CX43) expression was found in cadherin-5+ (Cdh5+) brain vascular cells of naturally aging mice and confirmed in human brain samples. Global or Cdh5+ cell-specific deletion of CX43 in mice exacerbates blood-brain barrier dysfunction during aging.

The CX43-dependent effects are not due to its canonical gap junction function but are related to reduced NAD+ levels and mitochondrial dysfunction via NAD+-dependent sirtuin 3 (SIRT3). CX43 interacts with and negatively regulates PARP1.

Pharmacological inhibition of PARP1 via Nicotinamide Mononucleotide (NMN) supplementation rescues NAD+ levels and alleviates aging-related blood-brain barrier leakage.

These findings establish the role of the CX43-PARP1-NAD+ pathway in vascular aging and identify a potential therapeutic strategy of NMN supplementation to counteract aging-associated blood-brain barrier leakage with neuroprotective effects.

With the process of aging, cognitive impairment and neurological abnormalities are inevitable topics. Fortunately, supplementing NMN to combat aging-related blood-brain barrier leakage is beneficial to saving the occurrence of cognitive impairment.

*Special note - This article is for informational purposes only and cannot replace a doctor's treatment diagnosis and advice. It should not be regarded as a recommendation or proof of efficacy of the medical products involved. If it involves disease diagnosis, treatment, and rehabilitation, please be sure to go to a professional medical institution to seek professional advice.