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How I Grabbed the #1 Spot in the Rejuvenation Olympics and Reduced My Epigenetic Age by 6 years in 1 year
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Introduction:

Hi everyone, I am u/daniellewis4life, the current occupant of the #1 spot in the Rejuvantion Olympics [see HERE and https://imgur.com/a/0kBCcE7 ]. I've managed to beat several longevity influencers, including Bryan Johnson. People have been reaching out to me on instagram for details of my protocol, but it is hard to write long posts on there, so I am publishing my full protocol with data here so that it is easily accessible for everyone.

When I turned 34 in 2023 I decided it was time for me to upgrade my fight against aging. I am a lawyer who had been following longevity research for fun for the prior 12 years. Up until 2023, to fight aging I had only used the lifestyle basics of (i) Mediterranean diet (fish, chicken, veggies, olive oil), (ii) intermittent fasting (18:6 skipping breakfast), (iii) 10%  calorie restriction, (iv) regular vigorous exercise (cardio weightlifting), (v) quality sleep, and (vi) limiting consumption of alcohol and sweets. All this on its own, plus some help from good genetics from my wonderful 94 year old grandmother,  was still enough to get me a DunedinPACE of aging score of 0.6 (i.e. 0.6 epigenetic years aged per chronological year) and put me at the top of the RejuvenationOlympics. I wasn't satisfied though. I didn't want to just age more slowly - I wanted to try and reverse my age!

Testing: 

In July 2023 I sent off my blood for some tests to establish some baseline values.

1.TruAge Complete test by Trudiagnostic - This test measures the following estimates of biological age:

(i) Dunedin PACE - an epigenetic estimate of pace of aging developed at Duke University,

(ii) SymphonyAge - an epigenetic estimate of the age of 11 different organ systems and a composite age calculated from the same, developed at Yale University,

(iii) OmicAge - a  epigenetic estimate of age that is very comprehensive and difficult to change, developed at Harvard University,

(iv) An epigenetic estimate of Telomere length,

(v) Immune Cell Composition and estimate of immune age,

(vi) An epigenetic estimate of inflammation,

(vii) Cellular division rate,

(viii) An epigenetic estimate of dieting response,

(ix) An epigenetic estimate of exercise fitness.

  1. Iollo - This test estimates your biological age by measuring the levels of 600 metabolites in the blood.

  2. Siphox - This test measures the basics, like HDL and LDL cholesterol, hormones, etc.

Theoretical Foundation:

The theoretical foundation for my protocol is that the various manifestations of aging are primarily caused by stem cell telomere attrition and epigenetic dysregulation. I believe the recent papers on partial cellular reprogramming strongly support this theory by showing that when a cell's epigenetics are partially restored, its transcriptomic, proteomic, and metabolomic status improve as well.

Protocol:

My protocol consisted of maintaining my aforementioned diet and lifestyle habits, while taking the following  supplements every day:

(1) 600 mg of liposomal Ca-AKG,

(2) 8 mg of liposomal spermidine,

(3) 1 gram of liposomal vitamin C,

(4) a liposomal blend of 250mg of NMN, 180 mg of NAD , and 160 mg of NR,

(5) 75 mg of liposomal green tea extract standardized to contain 70% EGCG.

I chose the above supplements based on research showing that:

(1) AKG is able to enhance the function of the cellular TET enzymes and thereby remove harmful dna methylation, as well as research showing that it prolonged the lifespan, fertility, and healthspan of rats,

(2) Spermidine is able to stimulate autophagy and modulate mTOR, help preserve telomere length, and prolong the lifespan, fertility, 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 too numerous to list here,

(4) NAD is able to activate the sirtuins and thereby improve dna repair, maintain telomere length, and remove harmful dna methylation

(5) EGCG helps prevent dna damage, extends lifespan of rats, and may have benefits for maintaining the epigenome by acting as a dna methyltransferase inhibitor.  

Sourcing:

I sourced my supplements from the company RenueByScience. I chose this company after considering their product selection, their liposomal formulations (liposomal administration greatly enhances supplement bioavailability), and their regularly published third-party lab results confirming the purity of their products and the accuracy of their labeling. I was also confident in choosing this company after reading that two independent labs conducting audits of the supplement industry found their NMN to be pure and to match the quantities stated on their label. Remember that the supplement industry is poorly regulated and as consumers we are dependent on the goodwill of supplement manufacturers (and occasional third party lab audits) to ensure that our supplements actually contain what is on the label!

Results:

For the next 12 months I followed the above protocol while keeping my lifestyle the same. My lifestyle changed somewhat at the halfway point because I caught two nasty respiratory viruses that threw off my exercise protocol for a while (this winter was rough!). At the end of the 12 months I repeated all of the tests to measure my improvement.

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. I used the AI program NOVOS FaceAge to assess my face age and it found a small reduction in face age with a large reduction in the age of my eye area. The real interesting results are with the testing data though!

1(i). Dunedin PACE:

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)! I managed to stay around this value during the 12 months of my protocol. [https://imgur.com/C6vIbur ]

1(ii). SymphonyAge:

My composite organ epigenetic age decreased from 26 to 20, and my epigenetic age declined for each organ system. [see https://imgur.com/rHNOymF  for a chart showing change over time, and https://imgur.com/KoBL4CB  for current results]

Research suggests that SymphonyAge is the most useful of the current epigenetic clocks for predicting diseases of specific organ systems.

1(iii). OmicAge:

My OmicAge reduced by 1.6 years. [See https://imgur.com/ZZ3VIoY  for before and after]

OmicAge is hard to change because it measures methylation of about 1,000 CpG sites that research suggests are causal (as opposed to correlational) for aging.

1(iv). Epigenetic estimate of Telomere length:

My epigenetic proxy of telomere length went from that of a 27 year old to that of an 18 year old [see https://imgur.com/Hr7e1xN for before, and https://imgur.com/Q1kNSuQ for after].

I think this result was entirely attributable to the NAD precursors, because there is research suggesting that increasing cellular NAD levels reduces the telomere attrition that occurs when somatic cells differentiate from stem cells.

1(v). Immune Cell Composition and estimate of immune age:

My immune cell composition and immune cell ratios became much healthier. [see https://imgur.com/undefined  for before, and https://imgur.com/P4SFzDp  for after].

My immune cell counts and ratios are now similar to those of an 18 year old. You will note that my numbers of naive T cells and naive B cells increased considerably, which indicates that I have newly produced immune cells circulating in my blood. Greg Fahy, in his experiments on thymic rejuvenation, found increased numbers of these naive immune cells in his subjects. This leads me to hope that I have partially rejuvenated my thymus, and to support this hope I found recent research that calorie restriction partially rejuvenated the thymus of human subjects. [SOURCE] Also, another study found that alpha ketoglutarate was able to prevent thymic involution in rats subjected to endotoxin. [SOURCE]

1(vi). Epigenetic estimate of inflammation:

The epigenetic estimates of CRP and IL-6, two different measures of inflammation, improved [see https://imgur.com/MmOCYDA  for before and after].

In particular, the epigenetic estimate of IL-6 ( a marker of cellular senescence) collapsed to very low levels. My epigenetic estimate of CRP initially worsened (likely due to sickness during winter) but then began to fall back to baseline values.

1(vii). Cellular division rate:

My estimate of cellular division rate decreased [see https://imgur.com/MGCToss  for before, and https://imgur.com/hIX6Tad  for after].

You will note that my cellular division rate was already low at baseline, likely due to my intermittent fasting and calorie restriction. Research suggests that lower cellular division rates reflect a lower risk of cancer. Lower cellular division rates also place less of a burden on your stem cell populations, which should preserve your stem cell populations and hopefully increase life expectancy.

1(viii). An epigenetic estimate of dieting response:

My response to dieting, as predicted by my epigenetics, improved slightlty [see https://imgur.com/undefined  for before, and https://imgur.com/BROKSMN  for after]. 

1(ix).  An epigenetic estimate of exercise fitness:

My epigenetic estimate of exercise fitness initially worsened due to sickness during winter and the resultant lack of exercise before then partially improving [see https://imgur.com/096XpWU  for before and after].

This score is a composite score based on epigenetic estimates of grip strength, gait speed, VO2 max, and FEV1.

 2. Iollo:

My Iollo metabolomic age, which is derived from the levels of over 600 chemicals in my blood, decreased by 3 years.

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 metabolites produced by cells to have a more youthful composition. I think my score on this test may be less helpful going forward, because I it appears that  chronological age is one of the variables used by Iollo to calculate metabolomic age. This means that as I age chronologically, my Iollo metabolomic age estimate will continue to increase, even if my metabolomics continue to improve.

  1. Siphox:

My values either stayed the same or improved. I had a significant decline in CRP, LDL cholesterol, and total cholesterol. HDL cholesterol declined but not as much as LDL cholesterol. Testosterone increased.

Conclusion:

I am very happy with the results of my protocol. In 12 months, I managed to improve in almost all of the measures of biological age that I tested. In some of the measures I improved very significantly. For example, my composite SymphonyAge score decreased by 6 years in 12 months!

I plan to continue my current protocol, but I will be adding some supplements. I will retest in 6 to 12 months to see how I have progressed. I will update this subreddit with new data as it becomes available. Let's see how long I can keep the #1 spot on the Rejuvenation Olympics.

If you have questions for me, please respond to this post and I will try to answer them. I hope the information I have provided here helps someone in their health journey. Good luck everyone!

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