Blood-brain barrier decreases with age, how to restore it

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Asked Perplexity AI 4 questions: May 2024

How much does the blood-brain barrier decrease in seniors?

The blood-brain barrier (BBB) undergoes several changes with aging, which can lead to increased permeability and decreased functionality. Here are some key points from the sources provided:

1. Increased Permeability: Aging is associated with increased BBB permeability. This is evidenced by higher cerebrospinal fluid (CSF)/serum albumin ratios, indicating increased capillary permeability in the brain. Studies using dynamic contrast-enhanced (DCE) MRI have shown that BBB leakage rates are higher in older adults, particularly in brain regions most vulnerable to age-related deterioration.
2. Structural and Functional Changes: The structural integrity of the BBB deteriorates with age. This includes changes in the tight junction proteins, such as occludin-1 and ZO-1, which are crucial for maintaining the barrier's integrity. Additionally, there is a reduction in the expression of transport proteins like P-glycoprotein, which affects the BBB's ability to remove neurotoxins from the brain.
3. Inflammation and Neuroinflammation: Aging is associated with increased neuroinflammation, which can further compromise BBB integrity. Elevated levels of inflammatory cytokines like TNF-α have been observed in aged brains, contributing to BBB disruption.
4. Pericyte and Astrocyte Changes: Loss of pericytes and increased astrocytic reactivity are also associated with BBB disruption in aging. Pericytes play a crucial role in maintaining BBB integrity, and their loss can lead to increased permeability.
5. Mixed Evidence in Animal Models: While some animal studies have shown increased BBB permeability with aging, others have not found significant changes. This discrepancy suggests that the extent of BBB permeability changes with age may vary depending on the specific conditions and methods used in the studies.

In summary, the BBB does decrease in functionality and integrity in seniors, primarily through increased permeability, structural changes, and heightened inflammation. These changes can contribute to the vulnerability of the aging brain to neurodegenerative diseases and cognitive decline.
Click here for references

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How might the blood-brain barrier be restored or improved in seniors?

Restoring or improving the blood-brain barrier (BBB) in seniors is a multifaceted challenge that involves addressing the structural and functional changes that occur with aging. Several strategies have been explored and proposed based on recent research:
Pharmacological Interventions

1. Resveratrol: This naturally occurring compound found in foods like red grapes and dark chocolate has shown promise in restoring BBB integrity. In Alzheimer's patients, resveratrol reduced neuronal inflammation and slowed cognitive decline by decreasing the levels of matrix metalloproteinase-9 (MMP-9), which is associated with BBB breakdown. 2016 reference
2. Renin-Angiotensin System Drugs: Certain antihypertensive drugs that cross the BBB, such as AT1-receptor blockers and angiotensin-converting enzyme inhibitors, have been linked to better cognitive outcomes in seniors. These drugs may help maintain BBB integrity and reduce the risk of dementia.
3. Levamisole: This compound, used clinically to combat hookworm, has been shown to restore selective protein transport across the BBB in old mice, suggesting potential for reversing age-related BBB dysfunction.
4. Lipoic Acid: This antioxidant has been found to restore age-associated impairments in brain energy metabolism and improve BBB function through modulation of specific signaling pathways.

Lifestyle and Nutritional Interventions

1. Physical Exercise: Regular physical activity has been shown to reduce BBB permeability by enhancing antioxidative capacity, reducing oxidative stress, and improving endothelial function. Exercise may also increase the density of brain capillaries, contributing to better BBB integrity.
2. Dietary Supplements: Nutritional compounds such as curcumin, sulforaphane, and omega-3 fatty acids have been shown to have anti-inflammatory and antioxidative effects that can help maintain or restore BBB integrity. Vitamin D, in particular, is noted for its role in reducing inflammation and supporting BBB function. Reference__

Advanced Therapeutic Approaches

1. Nanoparticle-Based Drug Delivery: Researchers are developing nanoparticles that can cross the BBB and deliver drugs directly to the brain. These nanoparticles can be engineered to target specific cells involved in neuroinflammation, potentially improving drug delivery and efficacy in treating neurodegenerative diseases.
2. Ultrasound Techniques: A novel skull-implantable ultrasound device has been used to temporarily open the BBB, allowing chemotherapy drugs to reach the brain in glioblastoma patients. This technique could be adapted for delivering other therapeutic agents to the brain in seniors.
3. WNT Signaling Pathway Activation: Drugs that activate the WNT signaling pathway have shown potential in restoring BBB integrity by promoting cell-to-cell communication in brain blood vessels. This approach has been effective in animal models and holds promise for treating various neurological diseases.

Research and Future Directions

1. Microbial-Derived Metabolites: Recent studies have explored the role of gut microbiota in modulating BBB function. Microbial-derived metabolites may offer new avenues for protecting and restoring BBB integrity.
2. Biomarker Development: Identifying specific biomarkers for BBB dysfunction can help in early diagnosis and targeted treatment of BBB-related issues in seniors. This could lead to more personalized and effective therapeutic strategies.

In conclusion, a combination of pharmacological, lifestyle, and advanced therapeutic approaches holds promise for restoring or improving the BBB in seniors. Ongoing research is crucial to fully understand the mechanisms involved and to develop effective treatments.
Click here for references

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Might the decrease in cognition with aging be associated with the decrease of the blood brain barrier with aging?

Yes, the decrease in cognition with aging is associated with the deterioration of the blood-brain barrier (BBB). Several studies have highlighted the relationship between BBB dysfunction and cognitive decline in aging.

1. Blood-Brain Barrier Changes with Aging: The BBB undergoes significant changes during normal aging, including increased permeability, reduced transporter function, and structural alterations. These changes can lead to a less effective barrier, allowing harmful substances to enter the brain and potentially contribute to cognitive decline.
2. Impact on Cognitive Function: The breakdown of the BBB has been linked to cognitive impairment and neurodegenerative diseases such as Alzheimer's disease. Increased BBB permeability can result in the infiltration of toxins and inflammatory substances into the brain, which can disrupt neural function and contribute to cognitive deficits.
3. Mechanisms of BBB Dysfunction: Aging affects various components of the BBB, including endothelial cells, tight junctions, and transporters. For example, the expression of glucose transporters (Glut1) and efflux transporters (P-glycoprotein) decreases with age, impacting nutrient delivery and waste removal from the brain. Additionally, structural changes such as thickening of the basement membrane and alterations in the extracellular matrix can further compromise BBB integrity.
4. Cognitive Decline and Neurodegenerative Diseases: Studies have shown that BBB breakdown is an early biomarker of cognitive dysfunction and is associated with the progression of neurodegenerative diseases. For instance, individuals with mild cognitive impairment (MCI) and Alzheimer's disease often exhibit increased BBB permeability, which correlates with cognitive decline.
5. Research Findings: Research using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has demonstrated that BBB leakage is more prevalent in individuals with cognitive impairment, including those with vascular mild cognitive impairment (vMCI) and Alzheimer's disease. This increased permeability is associated with decreased cognitive function, suggesting a direct link between BBB integrity and cognitive health.
   "Blood-brain barrier link to human cognitive impairment and Alzheimer’s Disease" 2022 10.1038/s44161-021-00014-4 Free PDF
   "Increase of blood-brain barrier leakage is related to cognitive decline in vascular mild cognitive impairment" April 2021 https://doi.org/10.1186/s12883-021-02189-6 FREE PDF

In summary, the decrease in cognition with aging is closely associated with the deterioration of the BBB. The breakdown of this critical barrier allows harmful substances to enter the brain, contributing to neural dysfunction and cognitive decline. Understanding these mechanisms is crucial for developing strategies to protect BBB integrity and mitigate age-related cognitive impairment.
Click here for references

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Is it possible that the BBB can be maintained by supplements such as Vitamin D or Omega-3?

Yes, it is possible to maintain the integrity of the blood-brain barrier (BBB) with supplements such as Vitamin D and Omega-3 fatty acids. Several studies have demonstrated the beneficial effects of these supplements on BBB function.
Vitamin D
Vitamin D has been shown to play a significant role in maintaining BBB integrity through various mechanisms:

• Reduction of Reactive Oxygen Species (ROS): Vitamin D helps block the increased production of ROS and nuclear factor kappa B (NF-κB) activation, which are known to damage the BBB.
• Enhancement of Tight Junction Proteins: Vitamin D increases the levels of tight junction proteins such as occludin, claudin-5, and ZO-1, which are crucial for maintaining the BBB's selective permeability.
• Anti-Inflammatory Effects: Vitamin D supplementation has been shown to reduce brain edema and BBB disruption induced by traumatic brain injury (TBI), as well as decrease the inflammatory response in the brain.
• Neuroprotective Properties: Vitamin D can preserve cognitive functions and inhibit brain dysfunction in disease models, acting as an anti-inflammatory, antioxidant, and neuroprotective agent.

Omega-3 Fatty Acids
Omega-3 fatty acids, particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), also contribute to BBB maintenance:

• Anti-Inflammatory Effects: Omega-3 fatty acids have been shown to reduce inflammation, which is a key factor in BBB disruption.
• Protection Against BBB Disruption: Studies have demonstrated that omega-3 fatty acids can protect against BBB disruption induced by surgery or other stressors, maintaining endothelial tight junctions and reducing permeability.
• Transport Mechanism: Omega-3 fatty acids cross the BBB via specific transporter proteins like MFSD2A, which facilitate their entry into the brain and help maintain BBB integrity.
• Combined Effects with Vitamin D: Co-supplementation of omega-3 fatty acids and Vitamin D has shown synergistic effects in reducing neuroinflammation and improving BBB function, particularly in conditions like TBI.

Conclusion
Both Vitamin D and Omega-3 fatty acids have been shown to support the integrity of the BBB through various mechanisms, including reducing oxidative stress, enhancing tight junction proteins, and exerting anti-inflammatory effects. These supplements can be effective in maintaining BBB function and potentially preventing or mitigating neurodegenerative diseases and cognitive decline associated with aging.
references are on-line

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How to heal a leaky blood brain barrier (with nootropics) 19 minute video

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Natural Ways to Fix a Leaky Blood-Brain Barrier in Functional Neurology Part 1 - Dec 2019

Improve Gut Health. ...
Avoid Eating Gluten. ...
Eat Food with Sulforaphane. ... (which activates the Vitamin D Receptor)
Eat Food with Resveratrol (which activates the Vitamin D Receptor) or Pterostilbene. ...
Drink More Coffee. ...
Take Omega-3 Fatty Acids. ...
Take Melatonin and Improve Sleep. ...
Manage and Reduce Stress.
Linkedin Dec 2019

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VitaminDWiki – Resveratrol improves health (Vitamin D receptor, etc.) contains

• The Vitamin D Receptor can restrict how much of the Vitamin D in the blood actually gets to cells
• Resveratrol is one of 14+ ways to negate the Vitamin D Receptor restrictions
• Resveratrol is produced by several plants in response to injury or, when the plant is under attack by pathogens such as bacteria or fungi
• Benefits of Resveratrol, like Vitamin D, appear to be increased when used with other things
  • Quercetin and Curcumin in the case of Resveratrol

18 articles in both of the categories Resveratrol and Vitamin D Receptor

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9+ VitaminDWiki pages have both BLOOD AND BRAIN in the title

This list is automatically updated