Approximately 25% of the general population carries at least one ε4 allele of the Apolipoprotein E (APOE ε4), the strongest genetic risk factor for late onset Alzheimer’s disease. Beyond its association with late-onset dementia, the association between APOE ε4 and change in cognition over the adult life course remains uncertain. This study aims to examine whether the association between Apolipoprotein E (APOE) ε4 zygosity and cognition function is modified between midlife and old age.
Compared to non-carriers, heterozygote (prevalence 25%) and homozygote (prevalence 2%) APOE ε4 carriers had increased risk of dementia, sub-distribution hazard ratios 2.19 (95% CI 1.73, 2.77) and 5.97 (95% CI 3.85, 9.28) respectively. Using data spanning 45–85 years with non-ε4 carriers as the reference, ε4 homozygotes had poorer global cognitive score starting from 65 years; ε4 heterozygotes had better scores between 45 and 55 years, then no difference until poorer cognitive scores from 75 years onwards. In analysis of individual cognitive tests, better cognitive performance in the younger ε4 heterozygotes was primarily attributable to executive function.
The ε4 allele of the Apolipoprotein E (APOE) gene is the strongest genetic risk factor for late onset Alzheimer’s disease (AD) [1]. Around 25% of the Caucasian population carries at least one ε4 allele [2], with a 3-fold increased risk of AD for heterozygotes and a nearly 15-fold increased risk for homozygotes compared to the ε3 homozygotes, the most common genotype [3].
The mechanisms underlying the relationship between APOE ε4 and AD are thought to be complex [5], involving, e.g., β-amyloid (Aβ) peptide clearance [6], neuronal death [7], and phosphorylation of tau [8].
In addition to AD, APOE ε4 plays a role in other causes of dementia, including vascular dementia [9], and Lewy Body disease [10]. Although case-control and longitudinal studies have examined the association of APOE with dementia, its association with cognitive decline over the adult life course remains debated [11, 12]. Some studies show accelerated cognitive decline in APOE ε4 homozygotes but not heterozygotes [13,14,15].


Furthermore, the association between APOE ε4 and cognition is thought to be modified by age; some [16,17,18] but not all studies [19, 20] report better cognitive performance among ε4 carriers at younger ages. The antagonistic pleiotropy hypothesis [21, 22], whereby a gene is thought to have different effects on health during different life stages, is a possible explanation for the age-varying association of APOE ε4 with cognitive performance over the life course [18, 22, 23].


However, much of the research on APOE is based on adults older than 65 years, followed for less than 10 years, making it difficult to ascertain how APOE shapes cognitive performance over the life course.

Link - https://alzres.biomedcentral.com/articles/10.1186/s13195-020-00740-0#Sec2

Combining berberine, quercetin, and piperine (black pepper extract) in a single supplement is relatively uncommon.

However, some formulations include these ingredients to enhance absorption and efficacy.

For instance, Pure Encapsulations offers a supplement called "Curcumin with Bioperine," which contains curcumin and piperine to improve bioavailability.

While this product doesn't include berberine or quercetin, it exemplifies the use of piperine to enhance nutrient absorption. (https://www.health.com/best-joint-supplements-8683190?utm_source=chatgpt.com))

If you're interested in a supplement that combines berberine, quercetin, and piperine, you might consider taking them separately or consulting with a healthcare provider to ensure appropriate dosing and to avoid potential interactions.

It's important to note that while piperine can enhance the absorption of certain compounds, it may also affect the metabolism of various medications, so professional guidance is recommended.

https://www.verywellhealth.com/best-berberine-supplements-8704634

If you are in the your 30-40 years old you should know, that you have about 350,000 hours left, unless you help yourself by investing anything you have (time, efforts, money & etc) into any longevity company or research

Spices for Longevity: Turmeric’s Anti-Aging Properties 🌱

Turmeric, known for its bright yellow color, contains curcumin, a compound with powerful anti-inflammatory and antioxidant effects. Studies suggest that curcumin can help reduce the risk of chronic diseases like heart disease, Alzheimer's, and cancer. Regular consumption of turmeric may contribute to longevity by protecting cells from damage.
Learn more about turmeric’s benefits [here](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664031/).

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How Green Spaces Impact Longevity 🌳

Living near green spaces, like parks or forests, has been shown to reduce stress, lower blood pressure, and improve mental health. A study from *Environmental Health Perspectives* found that people living close to nature had a lower risk of mortality from chronic diseases. Spending time in green spaces may be a natural way to extend lifespan.
Discover more about the impact of green spaces on longevity [here](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851085/).

---

Mindfulness for Healthy Aging: Slowing Down the Clock 🧘

Practicing mindfulness has been linked to lower levels of stress and improved emotional well-being. Research shows that mindfulness can reduce inflammation, improve immune function, and even slow cellular aging. A study from *Biobehavioral Medicine* found that mindfulness practices positively influence telomere length, a marker of biological aging.
Read more about mindfulness and aging [here](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189422/).

---

Fiber-Rich Diet for a Longer Life 🌾

A diet high in fiber, particularly from whole grains, fruits, and vegetables, is linked to lower risks of heart disease, diabetes, and even cancer. Fiber supports digestive health, reduces inflammation, and helps regulate blood sugar. Research from *The Lancet* suggests that people with high fiber intake have a reduced risk of early death.
Learn more about the longevity benefits of fiber [here](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647660/).

---

How Proper Sleep Hygiene Extends Lifespan 🛌

Quality sleep is crucial for your health and longevity. Studies show that poor sleep is linked to an increased risk of diseases like heart disease and diabetes. Practicing good sleep hygiene—like maintaining a consistent sleep schedule and avoiding screens before bed—can help improve sleep quality and support a longer, healthier life.
Find out more about the link between sleep hygiene and longevity [here](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5449130/).

---

Vitamin E: An Antioxidant for Anti-Aging 🥜

Vitamin E is a powerful antioxidant that helps protect cells from oxidative damage, which can accelerate aging. It also supports immune function and skin health. Studies suggest that regular intake of vitamin E through foods like nuts and seeds may slow aging and reduce the risk of chronic diseases.
Discover the benefits of vitamin E for aging well [here](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766596/).

Incorporation of photosynthetically active algal chloroplasts in cultured mammalian cells towards photosynthesis in animals
https://www.jstage.jst.go.jp/article/pjab/advpub/0/advpub_pjab.100.035/_article

Elon Musk fight the Death

Hi fellows!

Yesterday had a chance to introduce AI simulations of clinical trials in online symposium in Brussels. Will share the video soon.

Thanks to Didier Couernelle the organizer!

We have about 350,000 hours (40 years) left and we don’t have up to 15 years (38% of the time left) to wait for all stages of clinical trials to pass to bring fundamental scientific interventions to market, with about 8% chance that they will succeed!

AI simulations one of the solutions

Here is the link to presentation.

https://docs.google.com/file/d/1ktbWxv_CKLysHtKkmanmhIdOm8-9udtt/edit?usp=docslist_api&filetype=mspresentation

Maybe it’s not the best and not the only solution, but we all need to diversify our approach and use ALL options.

If you are interested to donate to our work, use a link for a donation platform or contact me directly.

https://gogetfunding.com/track-earky-live-longer/

Please note, that you leave tips in restaurants every day more than you donated to this kind of research!

Thanks

Oleg Teterin

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