My conclusion: Means CaAKG is maximally significant! My first in world guarantee of a "backward ageing (get younger) or money back" will work!!
https://www.aging-us.com/article/203736/text#fulltext
No true journal can do it faster… Received: October 5, 2021; Accepted: November 15, 2021 Published: November 30, 2021; must be super-important
Priority Research Paper Volume 13, Issue 22 pp 24485—24499
Rejuvant®, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8 year reduction in biological aging, after an average of 7 months of use, in the TruAge DNA methylation test
Oleksandr Demidenko1, * , Diogo Barardo2, * , Valery Budovskii1 , Robb Finnemore3 ,Francis R. Palmer III3 , Brian K. Kennedy2,3,4,5 , Yelena V. Budovskaya1
- 1 TruMe Inc., Alameda, CA 94502, USA
- 2 Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University Singapore, Singapore 117456, Singapore
- 3 Ponce de Leon Health, Fernandina, FL 32034, USA
- 4 Centre for Healthy Longevity, National University Health System, Singapore 117456, Singapore
- 5 Singapore Institute for Clinical Sciences, A*STAR, Singapore 117609, Singapore
* Equal contribution
Received: October 5, 2021 Accepted: November 15, 2021 Published: November 30, 2021
https://doi.org/10.18632/aging.203736
How to Cite
Copyright: © 2021 Demidenko et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
The search continues for possible interventions that delay and/or reverse biological aging, resulting in extended healthspan and lifespan. Interventions delaying aging in animal models are well established; however, most lack validation in humans. The length of human lifespan makes it impractical to perform survival analysis. Instead, aging biomarkers, such as DNA methylation (DNAm) clocks, have been developed to monitor biological age. Herein we report a retrospective analysis of DNA methylation age in 42 individuals taking Rejuvant®, an alpha-ketoglutarate based formulation, for an average period of 7 months. DNAm testing was performed at baseline and by the end of treatment with Rejuvant® supplementation. Remarkably, individuals showed an average decrease in biological aging of 8 years (p-value=6.538x10-12). Furthermore, the supplementation with Rejuvant® is robust to individual differences, as indicated by the fact that a large majority of participants decreased their biological age. Moreover, we found that Rejuvant® is of additional benefit to chronologically and biologically older individuals. While continued testing, particularly in a placebo-controlled design, is required, the nearly 8-year reversal in the biological age of individuals taking Rejuvant® for 4 to 10 months is noteworthy, making the natural product cocktail an intriguing candidate to affect human aging.
{Be;ievable aoolicable abstract. Brian Kennedy is Dr, Sinclair MIT classmate, himself accomplished, previous director of prestigious Buck institute (only sole aging in world) and now a top Singapore professor. Worked on CaAKG]
Introduction
Aging is a near universal biological process that manifests as a general decline in health and vitality, eventually leading to death. Aging is associated with the development of a wide range of chronic diseases, including cancer, Alzheimer's, diabetes, cardiovascular disease and many other conditions…
Aging is typically measured chronologically in days or years, with median human survival on the order of eight decades. … {DNAm Age uses methylation of Cytosine-phosphate-Guanine islands in epigenetics]]
… However, the most widely studied epigenetic mark is the direct methylation of DNA itself. …
The epigenetic clock is an attractive biomarker of aging because it applies to most human tissues, capturing aspects of biological age such as frailty, cognitive/physical fitness in the elderly, age-acceleration in obesity, premature aging in Down’s syndrome and HIV infection, Parkinson’s and Alzheimer’s disease-related neuropathologies, as well as cancer and lifetime stress. … of the most promising anti-aging compounds discovered to date is Alpha-Ketoglutarate (AKG) [23].
AKG is [moce tested] an endogenous intermediary metabolite in the Krebs cycle whose levels naturally decline during aging. … (delivered in the form of a calcium salt - CaAKG) on healthspan and lifespan in C57BL/6 mice was reported. …The effects of AKG on biological aging, and the possible correlation of other physiological effects, are discussed.
Results
For this study, we reviewed 42 participants who had elected to take Rejuvant® for a period of 4 to 10 months. [2 sex]…. The mean chronological age of this cohort was approximately 63 years old.
Table 1. Descriptive characteristics of the study participants.
Total Participants | 42 |
Gender (Female/ Male) | 14/ 28 |
Female: | |
Chronological Age (median; range) | 64.09; 43.49 to 72.46 |
Biological Age at Baseline (median; range) | 62.15; 46.4 to 73 |
Biological Age at T7* (median; range) | 55.55; 33.4 to 63.7 |
Male: | |
Chronological Age (median; range) | 62.78; 41.31 to 79.57 |
Biological Age at Baseline (median; range) | 61.85; 41.9 to 79.7 |
Biological Age at T7* (median; range) | 53.3; 33 to 74.9 |
*Indicates biological age as measured by TruMe test after an average of seven months of treatment. |
We assessed the prediction error of the TruAge epigenetic test, as previously described. Comparison of the predicted vs. actual age values yields a median absolute error of 4.23 years. ...
Figure 1. TruAge age estimation and baseline chronological age are linearly correlated. The TruAge biological age is highly (adjusted R-squared = 0.77) statistically significantly (p-value = 2x10-9) correlated with chronological age of the 42 patients.
We also considered whether there was a sex bias …
Figure 2. TruAge age estimation and baseline chronological age are linearly correlated, in both genders. The x-axis depicts DNA methylation age estimated by TruAge, and the y-axis the chronological age of the 42 patients at baseline. The pink and blue linear correlation plots depict the similarly high statistically significant linear correlation between both axes, for female and male patients, respectively.
Table 2. Effect of Rejuvant® on biological age of study participants.
Biological age distributions | Male participants (in years) | Female participants (in years) |
Minimum Biological Age at Baseline | 41.9 | 46.4 |
Median Biological Age at Baseline | 61.85 | 62.15 |
Mean Biological Age at Baseline | 61.38 | 61.09 |
Maximum Biological Age at Baseline | 79.7 | 73 |
Minimum Biological Age at T7* | 33 | 33.4 |
Median Biological Age at T7* | 53.3 | 55.55 |
Mean Biological Age at T7* | 53.53 | 54.66 |
Maximum Biological Age at T7* | 74.9 | 63.7 |
Minimum change in Biological Age | -1.86 | -0.41 |
Median change in Biological Age | 7.09 | 5.83 |
Mean change in Biological Age | 8.44 | 6.98 |
Maximum change in Biological Age | 22.7 | 14.09 |
*Indicates biological age as measured by TruMe test after an average of seven months of treatment. |
Participants completed a survey at the start and end of the trial. This self-reported questionnaire included information about diet, alcohol intake, previous consumption of Rejuvant®, health, height and weight (which allowed for estimation of BMI), sleep duration, smoking status, exercise frequency, physical activity level, meal frequency, snacking frequency, number of additional dietary supplements consumed and frequency, hair status, education, healthy lifestyle mindset and trust in dietary supplements (Supplementary Table 1).
We leveraged baseline survey information to check if there were other confounders in our cohort, performing a multivariable linear regression. Due to the considerable number of predicative variables, we performed a stepwise linear regression. Although there were additional covariates selected in the stepwise model, when this was compared, by means of analysis of variance, with the simpler univariate linear regression using solely the TruAge estimated age, the obtained p-value was 0.12 (Supplementary Table 2). This indicates that in terms of comparison, the two models are not statistically significantly different, and, therefore, the simpler model was selected.
It was of interest to determine whether the difference between chronological age and TruAge is related to lifestyle or demographic factors. … Therefore, it is likely that one or more of these lifestyle parameters influence the biological age as measured by the TruAge test and that a larger dataset would uncover associations.
Results of the CaAKG consumption on biological age
The goal of the study was to determine the effect of Rejuvant® supplementation [CaAKG similar] on human biological aging by measuring DNA methylation. …completion of the self-chosen treatment period, participants submitted their saliva samples for analysis of their biological age using commercially available TruMe tests.
Based on the questionnaires submitted at baseline and the end of the trial, we identified a subset of 13 individuals who reported no changes in diet type, drinking frequency, additional dietary supplements intake, sleep duration and exercise frequency. This homogeneous subset was therefore used for the preliminary assessment of the independent effect of CaAKG, as the other covariates are controlled for by design.
At baseline, this subset or our cohort was on average 2.06 years biologically younger than their chronological age. By the end …. Using one-sided Welch two sample paired t-test, this difference in m…It is noteworthy that every subject in this small group decreased their biological age. [Means CaAKG is maximally signeficant! My first in world guarantee of "backward aging or money back" will work!!]
Figure 3. CaAKG decreased methylation age among a homogeneous sub-population. The paired box plots represent the treatment effects at the patient and group level (n=13), between baseline and end of the trial (which on average had a duration of 7 months). The box plots depict the median and the 25th and 75th quartiles.
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