You CAN Turn Back Time

[Julie G]

Has anyone seen the recent study published by Kara Fitzgerald, MD and team demonstrating a reverse of biological age — Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial? It's very encouraging especially when you consider that the greatest risk factor for both cognitive decline and cardiovascular disease is aging and ApoE4 is associated with accelerated aging and inversely associated with longevity. Even more encouraging, Dr. Fitzgerald is using the exact same strategies that many of us are using including diet (very similar to KetoFLEX 12/3), exercise, stress management and sleep optimization. You can see a layman's breakdown of the study here: What is Biological Aging and What Does it Have to do with Methylation?

I'm joining her and Dr. Bredesen on a Facebook Live today at 11amPT to discuss her work. You can view it anytime on the Dale Bredesen, MD facebook page.

[Cat111]

Yes, great information. Looking forward to the new study that will hopefully include APOE4. I had just received my test results for myDNAage I'm 61 and 10 months and my test results says my biological is 63. I'm 4/4 with Bad MTHFR genes...have some work to do.

[circular]

Has anyone seen the recent study published by Kara Fitzgerald, MD and team demonstrating a reverse of biological age...

Thanks for posting this Julie. I've enjoyed some of Kara's podcasts along the way, but I had no idea she was involved with a clinical trial.

[circular]

Has anyone seen the recent study published by Kara Fitzgerald, MD and team demonstrating a reverse of biological age — Potential reversal of epigenetic age using a diet ...

I just found a similar, larger study a ... DAMA study (n=200+ postmenopausal women from the “Diet, Physical Activity, and Mammography” (DAMA) study; 2 years) [NB: Admins: The opening sentence was fused with the link to the paper and some words disappeared although my draft formatting is correct. Strange.]

Interestingly, they use DNAm GrimAge, a 'recently developed "next‐generation clock” [that] outperforms “first‐generation clocks” in predicting longevity and the onset of many age‐related pathological conditions and diseases.' A paper about this clock was published in 2019, before Dr. Fitzgerald's paper come out. Her paper indicates that she used an earler Horvath clock: 'DNAmAge was calculated using the online Horvath DNAmAge clock (2013)'.

I don't have much time to spend on this, but it appears that the older clock Dr. Fitzgerald used is based on whole genome sequencing to examine the specific methylation patterns, whereas DNAm GrimAge is based on biomarkers that have been shown to correlate with health and mortality outcomes, a correlation that's absent so far in Dr. Fitzgerald's still emerging work:

From the paper on the DNAm GrimAge approach:

It was unknown whether plasma protein levels can be estimated based on DNA methylation (DNAm) levels, and if so, how the resulting surrogates can be consolidated into a powerful predictor of lifespan. We present here, seven DNAm-based estimators of plasma proteins including those of plasminogen activator inhibitor 1 (PAI-1) and growth differentiation factor 15. The resulting predictor of lifespan, DNAm GrimAge (in units of years), is a composite biomarker based on the seven DNAm surrogates and a DNAm-based estimator of smoking pack-years. Adjusting DNAm GrimAge for chronological age generated novel measure of epigenetic age acceleration, AgeAccelGrim.

Using large scale validation data from thousands of individuals, we demonstrate that DNAm GrimAge stands out among existing epigenetic clocks in terms of its predictive ability for time-to-death (Cox regression P=2.0E-75), time-to-coronary heart disease (Cox P=6.2E-24), time-to-cancer (P= 1.3E-12), its strong relationship with computed tomography data for fatty liver/excess visceral fat, and age-at-menopause (P=1.6E-12). AgeAccelGrim is strongly associated with a host of age-related conditions including comorbidity count (P=3.45E-17). Similarly, age-adjusted DNAm PAI-1 levels are associated with lifespan (P=5.4E-28), comorbidity count (P=7.3E-56) and type 2 diabetes (P=2.0E-26). These DNAm-based biomarkers show the expected relationship with lifestyle factors including healthy diet and educational attainment.

Overall, these epigenetic biomarkers are expected to find many applications including human anti-aging studies. [Emphasis added]

The larger study that uses the DNAm GrimAge approach describes the dietary intervention used in DAMA this way:

Study participants assigned to the dietary intervention (arm 1) were counseled to adopt a diet based on the consumption of plant foods, with a low glycemic load, low in saturated‐ and trans‐fats and alcohol, and rich in antioxidants. The change in dietary habits was aimed to be achieved in an isocaloric context, as no advice was given about the quantity of food to be consumed. The intervention objectives included: (a) replacement of refined grains with whole grains; (b) consumption of at least one portion of raw vegetables and one portion of cooked vegetables at each meal; (c) consumption of fish at least 2–3 times weekly; (d) reduction of the consumption of fresh and processed red meat to less than once weekly; (e) consumption of at least 3–4 portions of legumes and pulses per week; (f) daily consumption of at least 2–3 portions of fruit; (g) cakes and desserts consumed no more than once weekly; (h) no more than 1 portion/day of milk or yogurt and 2 portions/week of cheese; (i) exclusive use of extra‐virgin olive oil as dressing and cooking fat; and (j) consumption of no more than one glass of wine daily at meals for those already used to drink alcohol.

It concludes:

We provided strong evidence of a causal association of improving dietary habits and increasing physical activity on DNAm‐based biomarkers of healthy aging. It is worthy to note that DAMA study is intentionally based on non‐extreme interventions, meaning that relatively easily achievable changes in one's lifestyle behaviors lead to a significant slowing down of biological aging biomarkers, which in turn are associated with higher longevity, lower risk of developing age‐related diseases, and increased quality of life in the older age. Further, our results indicate that dietary quality and physical activity influence epigenetic aging through complementary molecular mechanisms, suggesting that their effect is potentially cumulative rather than interchangeable. [Emphasis added]

[antimatter37]

For those interested in "life extension" overall, as well as its relationship to cognitive decline, here are a few recent podcasts from David Sinclair at Harvard Medical School:


https://www.youtube.com/watch?v=X1kLizzdb2c
https://www.youtube.com/watch?v=wD8reCw3Kls
https://www.youtube.com/watch?v=4Yc5EXX9YWg
https://www.youtube.com/watch?v=bRWT7hVgwuM
https://www.youtube.com/watch?v=RUiRFGX1Oqs

I find these very interesting, especially the ability to accurately measure biological age using the "Horvath Clock", which measures DNA methylation.

[circular]

Has anyone seen the recent study published by Kara Fitzgerald, MD and team demonstrating a reverse of biological age — Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial?

I listened to Dr. Rhonda Patrick's podcast episode released yesterday about the epigentics of age acceleration. She meets with Dr. Morgan Levine who did her postdoctoral fellowship with Dr. Steve Horvath. Dr. Levine states that the original epigentic clock that Dr. Fitzgerald used is highly unreliable and noisy. It was shown that if you take the same blood sample and run it twice through this original clock, you can get epigenetic clock results that differ up to eight years. When Dr. Levine was an advisor with Elysium Health she helped develop a statistical tool that removes the "technical noise" and reduces the variation to a maximum of one year while most split samples resulted in the same epigenetic age. They applied the statistical method that removes the noise to Dr. Fitzgerald's preliminary data and it showed "that the entire effect was noise." Hopefully in Dr. Fitzgerald's ongoing research she will upgrade the clock she uses to one of the newer ones.