6 replies to this topic

[dlewis1453]

Introduction: When I turned 34 in 2023 I decided it was time for me to upgrade my fight against aging. I had been following longevity research for the prior 12 years, but had not done anything to prevent aging other than the lifestyle basics of Mediterranean diet, intermittent fasting, mild calorie restriction, exercise, sleep, and restricting consumption of alcohol and sweets. 

 

Testing: So in July 2023 I sent off my blood for a TruAge Complete test by Trudiagnostic to establish my baseline values. This test measures (1)intrinsic epigenetic age (Horvath age), (2) extrinsic epigenetic age (Horvath Age + white blood cell composition), (3) Dunedin PACE, (4) methylation approximation of Telomere length, (5) OmicAge, and (6) epigenetic estimates of exercise fitness, responsiveness to weight loss, smoking, and alcohol consumption. In addition to TruDiagnostic, I took tests with Iollo (test that estimates age by measuring the levels of 600+ metabolites in the blood), Jinfiniti (test that measures cellular NAD+ levels), and GlycanAge (test that estimates age based on the quantity and composition of Glycans). I also uploaded pictures of my face to the Novos Face Age algorithm (a machine learning algorithm that predicts your age based on pictures of your face). 

 

Protocol: My protocol consisted of the following, taken every day: (1) 600 mg of liposomal Ca-AKG, (2) 8mg of liposomal spermidine, (3) 1 gram of liposomal vitamin c, (4) a liposomal blend of 125mg of NMN, 90 mg of NAD+, and 80 mg of NR, (5) 75 mg of liposomal  green tea extract standardized to contain 70% EGCG. If you would like to know the brand I used, send me a private message. I chose this brand after considering their product selection, their liposomal formulations, and their regularly published lab results confirming the purity of their products and the accuracy of their labeling.

 

Research: I chose this protocol based on research showing that: (1) AKG is able to enhance the function of the TET enzymes and thereby remove harmful epigenetic markers, as well as researching showing that it prolonged the lifespan and healthspan of rats, (2) spermidine is able to stimulate autophagy, help preserve telomere length, and prolong the lifespan and healthspan of mice, (3) vitamin c acts as a cofactor for the TET enzymes and may enhance the effectiveness of AKG, in addition to many other health benefits, (4) NAD+ is able to activate the sirtuins and thereby improve dna repair and maintain telomere length, and (5) EGCG helps prevent cancer and may have some benefits for maintaining the epigenome. 

 

For the next 8 months I followed the above protocol while trying keeping my lifestyle the same. My lifestyle changed somewhat because during those 6 months because I caught two nasty respiratory viruses that threw off my exercise protocol (this winter was rough!). 

 

Results: Attached at the bottom of this post you will find a picture of a chart with the results of my lab tests. Subjectively, while on this protocol I experienced increased energy, increased endurance in the gym, slightly decreased need for sleep, less grogginess in the morning, and a large reduction in eye puffiness/inflammation. 

 

 

Analysis of Results:

 

My intrinsic epigenetic age increased slightly less than would be expected for a 8 month period, but I was not able to achieve a reduction here. However, research shows that intrinsic epigenetic age is not very responsive to lifestyle interventions. Not even calorie restriction makes a significant change to it. Some research suggests that beneficial epigenetic changes actually get picked up as aging by this clock. 

 

My extrinsic epigenetic age declined substantially. Research shows that extrinsic epigenetic age is a better predictor of lifespan than intrinsic epigenetic age, so I am glad I achieved a strong result here. 

 

My Dunedin PACE was already excellent before starting my protocol (0.6 is supposed to be the lowest score a person can achieve on this test) but somehow I managed to improve my score even further to 0.58! 

 

My telomere length (as measured by epigenetics) improved slightly. The reliability of this measure of telomere length is subject to debate, but I am glad to see an improvement here anyway. 

 

My fitness age declined significantly. This is not surprising, given that I endured two strong respiratory viruses that weakened me and kept me from the gym during part of the protocol period. 

 

My OmicAge improved slightly. This is a very new measure of epigenetic age and its reliability is subject to much debate. According to TruDiagnostic, my OmicAge is lower than 85% of people at my chronological age. This suggests that OmicAge must be systematically overestimating the epigenetic age of test subjects, because my OmicAge is 4 years higher than my chronological age. 

 

My response to dieting (as measured by my epigenetics) improved greatly. I had benefited from dieting before during a weightlifting "cut" so I am suspicious of my initial test result that labeled me as a diet "non-responder." Regardless, I am happy with the improvement in this area. 

 

My Iollo metabolomic age, which is derived from the levels of over 600 chemicals in my blood, decreased moderately. I was very pleased with this result, because if gene expression is improving (reflected by improvements in epigenetic age) then we would expect for the chemicals circulating in my blood to have a more youthful composition. Unfortunately, I think this test will be less helpful going forward, because I realized that my chronological age is one of the variables used by Iollo to calculate my metabolomic age. 

 

My GlycanAge declined moderately, reflecting lowered levels of inflammation in my body. My GlycanAge started out quite higher than my chronological age, perhaps because I suffer from mild psoriasis and from gut dysbiosis. Although its interesting that my CRP results are always optimal. 

 

My NAD+ levels barely improved. I think because my dosage was too low. I was taking half the recommended dosage on the bottle. 

 

My Novos Face Age improved mildly, driven largely by the decrease in my under-eye age. I don't put much stock in the total face age score, because I found that I score much lower when I am clean shaven vs when I have stubble. However, I do think their measurement of the under eye area is reliable. Note though that sleep deprivation or dehydration can change the under-eye scores. 

 

Next Steps:

 

I am very pleased with the results of my protocol and view it as a success! For next steps, I will continue with my protocol and my regular testing, but I will be increasing my dosage of NAD+ precursors. I will also be adding in the following supplements on alternating days: astaxanthin, sulforaphane, pqq, leucine, vitamin b6, pterostilbene, liposomal glutathione, vitamin d, low dose lithium, and food-derived mixed carotenoids.  

 

 

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Edited by dlewis1453, 27 May 2024 - 10:31 PM.

[Mind]

Thanks for sharing the detailed data. Not too many supplement to achieve good results!

 

Some people might look at the results and think it was so-so, but at your young age, it is more difficult to achieve good results, because your rate of aging is quite slow. So any result toward younger biological age is dramatic.

[QuestforLife]

There has been a proliferation in the number of ageing measures and only time will tell what ends up being the most useful.

 

I think your results are good and that you should continue your protocol for a longer period and see what occurs. 

 

I did not find that Vit C enhanced the effects of AKG in my own experiments, but as you say, it has other benefits. You might want to try Vit A (although, again I didn't find additional benefit).

I would also recommend a liver function test every 6 months or so, just to make sure that you are not putting it under too much strain (AKG caused my ALT to rise). 

 

As Mind says, at your age, ageing hasn't really done much harm, so it would be hard for you to show much of a delta. There tends to be a shift around 40 or so, and by 45 to 50 you can tell the difference between slow and fast 'agers'. Even after that, you do get people who find a stable equilibrium in an aged state, and then go on for a long time. That's not straight forward to measure. 

[dlewis1453]

I have an update for the group!

 

TruDiagnostic, the company that I used for my epigenetic testing, has updated some of their values on the tests that I previously submitted. Consequently, some of the information in my previous post is now out of date. 

 

1. My values for my OmicAge, which is an epigenetic clock based on correlations between epigenetic marks and several hundred transcriptomic, proteomic, and metabolomic values, have been revised downward to 32.13 at baseline and 31.75 after 8 months of my protocol. This revision occurred because TruDiagnostic acquired a larger dataset that was more representative of the general population. From  looking at some of the data in the OmicAge report, it appears that OmicAge values cluster closely around chronological age until about age 40, after which there is a significant increase in dispersion of OmicAge scores. 

 

2. My fitness age values have also been revised downward for the same reason, to 21.45 at baseline and 31.18 after 8 months. Recall that I was sick twice with viruses during this time, so my performance in the gym suffered during this time. I am now feeling stronger and faster than I was even at the start of my protocol, so hopefully my fitness age at next testing will reflect my subjective improvements. 

 

3. TruDiagnostic has licensed a new epigenetic test from Yale called SymphonyAge. This epigenetic clock was developed by finding epigenetic marks that correlate with worsening in over 100 different biomarkers specific to 11 different organ systems. This approach makes SymphonyAge unique among the 2nd generation epigenetic clocks and enables the calculation of organ-specific epigenetic age. A composite epigenetic age score is then computed from the 11 organ-specific epigenetic ages. TruDiagnostic ran the SymphonyAge test on my previous samples and produced a composite age of 26 at baseline and 24 after 8 months of my protocol. I have attached screenshots of my before and after SymphonyAge results below. What is interesting is that I improved in 9 out of 11 organ systems, and the dispersion of my epigenetic age across organ systems greatly decreased, with a new grouping around 24 years of age for multiple organ systems. 

 

I have pasted a new results overview chart below. It has been a year since the start of my protocol, so I will be sending off new blood tests to see how things have progressed. Thanks to Mind and QuestForLife for commenting on my results. I will be starting an expanded version of my protocol now, which I discussed in my prior post. We will see what results version 2 of my protocol is able to achieve. 

 

 

  Baseline 8 months Improvement? Chronological Age 34 years old 34.67 years old N/A Trudiagnostic       Intrinsic Epi Age 35.9 years old 36.34 years old Mild Worsening Extrinsic Epi Age 30.42 years old 18.24 years old Major Improvement Dunedin PACE 0.6 bio aging per chrono year 0.58 bio aging per chrono year Mild Improvement      (note, 0.6 is supposedly the minimum score) Telomere Age (methylation estimate) 27.26 years old 26.9 years old Mild Improvement SymphonyAge (composite) 26 years old 24 years old Moderate Improvement Omic Age 32 years old 31 years old Mild Improvement Epi-Fitness Age 21.45 31.18 Moderate Worsening Epi-Response to Dieting 100% non-responder 50% responder Moderate Improvement Iollo 34.1 years old 31.5 years old Moderate Improvement Siphox n/a n/a all values improved or stayed the same Jinfiniti 33.8 μM 35.7 μM Mild Improvement Novos Face Age 30 28 Mild Improvement Under Eye Area 31 26 Moderate Improvement

 

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[Mountain]

Thanks for sharing. I am curious to understand why you chose TruDiagnostic to perform your aging test. There are many others, such as Nebula Genomics, thus what made you thinkTrudiagnostic was your best pick and what are the other options worth considering?

Thanks.

[dlewis1453]

Thanks for sharing. I am curious to understand why you chose TruDiagnostic to perform your aging test. There are many others, such as Nebula Genomics, thus what made you thinkTrudiagnostic was your best pick and what are the other options worth considering?

Thanks.

 

From looking at the Nebula Genomics website it appears that they test your DNA, not your epigenetics, so it would not be applicable to what I am measuring here.

 

TruDiagnostic was my best choice because of the number of epigenetic tests that they include in their TruAge Complete kit. No other epigenetic testing company measures as much with a single kit. With a single kit, TruDiagnostic measures the Horvath clock, the Hannum clock, an epigenetic estimation of telomere length, OmicAge (an epigenetic measure of your transciptomics, proteomics, and metabolomics), SymphonyAge ( epigenetic age of 11 different organ systems), analysis of the composition of your immune cells, an epigenetic estimation of your physical fitness, an epigenetic estimation of your response to dieting, an epigenetic estimation of your exposure to alcohol and cigarettes, and the Dunedin Pace of Aging epigenetic test.

 

I would add that TruDiagnostic is the only epigenetic testing company that offers OmicAge and SymphonyAge, two epigenetic tests created by researchers at Harvard and Yale, that are so-called "second generation" epigenetic clocks because they were developed by comparing many hundreds of DNA methylation sites against changes in actual health biomarkers. These two clocks are more predictive of mortality than the first generation clocks, such as the Horvath clock. The Dunedin PACE of Aging clock is also a second generation clock. 

Edited by dlewis1453, 23 August 2024 - 02:56 AM.

[dlewis1453]

Introduction: I have another update for the group! I have my TruDiagnostic test results for the 1 year anniversary of the start of my longevity protocol. I have made no changes to my protocol since my post in May 2024, except that I doubled my dosage of my NAD precursor blend because my previous dose was too low. For background, my chronological age is 35. I just turned 35 a couple of months ago. 

 

Here are the highlights: 

 

1. My OmicAge declined to 30.51. My baseline OmicAge was 32.13. This is a reduction of 1.62 years over one chronological year. See first attachment.
 

2. My composite Symphony Age declined to 20. My baseline composite Symphony Age was 26. This is a reduction of 6 years over one chronological year. Excitingly, I also managed to reduce my SymphonyAge in each of the 11 measured organ systems during this year. See second and third attachments. 

 

3. My Dunedin Pace increased to 0.67. My baseline Dunedin Pace was 0.6. This is a small increase. I was surprised by this result, since my OmicAge and SymphonyAge values decreased during this same time period. The Youtube Michael Lustgarten has written that higher doses of certain NAD precursors worsened his Dunedin Pace score, so maybe something similar happened to me here. See fourth attachment.

 

4. My epigenetic estimate of my telomere length increased to 7.63 Kb (equivalent to someone 18.4 years old). My baseline was 7.51 Kb (equivalent to someone 26 years old). See 5th and 6th attachment. Notably, my telomere length only increased after I doubled my NAD precursor dosage. In his thread here on Longecity called "Alternative Methods to Extend Telomeres," the user QuestForLife has written that increasing cellular NAD levels could greatly slow telomere shortening, and that this telomere shortening would be reflected in standard telomere tests as an increase in leukocyte telomere length. I believe that my results here are confirmation of this mechanism. 

 

5. My immune cell ratios are suggestive of improved immune function and reduced inflammation. See 7th attachment. Compared to baseline, I have larger percentages of naive CD4 T cells, naive CD8 T cells, and Naive B cells. My CD4/CD8 T cell ratio remained about the same, but I saw improvements in my Neutrophil to Lymphocyte ratio and my Lymphocyte to Monocyte ratio that are indicative of improved immune function and reduced inflammation. Interestingly, Greg Fahy, in his study on using growth hormone to regrow the thymus, observed increases in naive CD4 T cells and naive CD8 T cells in human subjects that experienced thymic regrowth. I wonder if my protocol is causing my thymus to regrow? There is some research to suggest that alpha ketoglutarate could help counteract thymic involution. See this paper https://pubmed.ncbi....h.gov/16844034/.

 

6. On the anecdotal front, things are the same. I have improved energy. I function well even when I don't get quite enough sleep. I don't suffer from jet lag. I have no grey hairs. No new wrinkles. My skin coloring and texture looks healthy. My under eye area appears healthier, with less darkness under the eyes. In the gym I have good energy, strength, and cardiovascular endurance.

 

Conclusion: 

 

Now that I have 1 year of data to reflect on, I can confidently say that I am very happy with my protocol and the progress I have made. It was interesting to see that increasing my dose of NAD precursors half way through the year appears to have led to an acceleration of benefits and a significant increase in telomere length, but perhaps at the expense of a slight worsening in Dunedin PACE score. The fact that my age decreased in each of the 11 SymphonyAge organ systems suggests that my protocol is broadly benefiting my body. Interestingly, the organ system ages that decreased the most were the immune, metabolic, inflammation, kidney, heart, and liver. Another interesting point is that the SymphonyAge appears to be more malleable than the OmicAge. From looking at the dispersion of OmicAge scores across a broad population, it appears that OmicAge closely tracks chronological age under the age of 40, but then experiences greater dispersion after the age of 40. 

 

You may be wondering why I did not report my new intrinsic and extrinsic epigenetic age (i.e. Horvath and Hannum ages). That is because TruDiagnostic no longer supports those epigenetic age measures. Since OmicAge and SymphonyAge are 2nd generation clocks that are more predictive of mortality than Horvath and Hannum age, I will rely on them instead going forward. 

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