Category Archives: aging.ai

Attempting To Further Reduce Biological Age: hs-CRP

Homocysteine Update, What’s Optimal For Vitamin B12?

Quantifying Biological Age With Aging.ai: 24 Blood Tests Since 2009

The maximal reduction for biological age when using the biological age calculator, Phenotypic Age, is ~20 years. In other words, if I’m 80 years old and my biomarkers are all reflective of youth, the lowest possible biological age will be ~60 years old. One reason for that is the inclusion of chronological age in the prediction of biological age, which adds strength to the correlation while simultaneously limiting the maximal biological age reduction.

To account for the possibility that youthful biomarkers at an older chronological age can yield a biological age that is more than 20 years younger, it’s important to quantify biological age using a tool that doesn’t include chronological age in its calculation. Aging.ai fits that criterion, and in the video I present biological age data with use of aging.ai for 24 blood tests since 2009.

Optimizing Biological Age With Aging.ai: Blood Urea Nitrogen

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Blood urea nitrogen (BUN) is one of the 19 variables found on the biological age calculator, aging.ai. It measures the amount of nitrogen, as contained in urea (i.e., blood urea nitrogen, BUN) in your blood. The reference range for BUN is 5 – 20 mg/dL, but within that range, what’s optimal?

First, BUN increases during aging, from 11 – 13 mg/dL in 20 yr olds to 20 – 22 mg/dL in 90 yr olds (Wang et al. 2017):

The importance of the age-related increase in BUN is illustrated by the finding that risk of death for all causes increases above 15 mg/dL:

Also note that maximally decreased risk for all cause mortality was associated with BUN values between 5 – 15 mg/dL. In addition, even though a BUN value = 20 mg/dL is technically within the reference range, risk of death for all causes would be 50% higher when compared with someone that had BUN levels between 5 – 15 mg/dL. Collectively, based on the aging and all-cause mortality data, I’d argue that 5 – 13 mg/dL may be the optimal range for BUN.

Assuming normal kidney function (see https://michaellustgarten.wordpress.com/2019/11/18/optimizing-biologic-age-creatinine/), if your BUN is higher than 15 mg/dL, can it be reduced? Note that urea production is almost perfectly correlated (r = 0.98) with dietary protein intake (Young et al. 2000):

In other words, the main source of dietary nitrogen is protein, so if you eat a lot of protein, you’ll make a lot of urea. Circulating levels of urea can be easily calculated by measuring BUN, via: Urea [mg/dL]= BUN [mg/dL] * 2.14). Therefore, measuring BUN can then be used to determine if your protein intake is too high or too low.

What’s my BUN? As shown below, I’ve measured BUN 22 times since 2015. In line with the Young et al. (2000) data that showed an almost perfectly linear correlation between dietary nitrogen intake with urea production, similarly, as my dietary protein intake has increased, so have my BUN levels. The correlation between my dietary protein intake with BUN is strong (r = 0.76, R^2 = 0.575, p-value = 4.3E-05):

Note that my BUN is (purposefully) below 15 mg/dL, the upper limit for reduced all-cause mortality risk in Solinger and Rothman (2013), and within the 11 – 13 mg/dL range reported for the 20 yr olds of Wang et al. (2017).

For more recent tracked data, see the video!

References

Solinger AB, Rothman SI. Risks of mortality associated with common laboratory tests: a novel, simple and meaningful way to set decision limits from data available in the Electronic Medical Record. Clin Chem Lab Med. 2013 Sep;51(9):1803-13.

Wang Z, Li L, Glicksberg BS, Israel A, Dudley JT, Ma’ayan A. Predicting age by mining electronic medical records with deep learning characterizes differences between chronological and physiological age. J Biomed Inform. 2017 Dec;76:59-68. doi: 10.1016/j.jbi.2017.11.003.

Young VR, El-Khoury AE, Raguso CA, Forslund AH, Hambraeus L. Rates of urea production and hydrolysis and leucine oxidation change linearly over widely varying protein intakes in healthy adults. J Nutr. 2000 Apr;130(4):761-6.

If you’re interested, please have a look at my book!

Podcast: Optimizing Biological Age with Dr. Michael Lustgarten, PhD.

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Here’s a recent podcast that was recorded with Julian Hayes II at Optimal Health for Busy Entrepreneurs:

https://theartoffitnessandlife.com/episode20/

Enjoy!

Which Blood Test Analyte Is Most Important For Predicting Biologic Age?

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Three studies have investigated the ability of blood test analytes to predict biological age. First, when considering the top 20 variables that were associated with biological age in aging.ai, albumin contributed most to this prediction, almost 2x more than circulating levels of glucose (Mamoshina et al. 2018):

Second, albumin was one of the 9 blood test variables that were best able to predict biological age when using the Phenotypic Age calculator. However, as shown below, it didn’t come in first place, but fifth. Interestingly, the analyte that contributed most to biological age prediction was the red cell distribution width (RDW%), with glucose again in second place (Levine et al. 2018):

Third, Earls et al. (2019) used the Klemera-Doubal algorithm (Klemera and Doubal, 2006) in conjunction with blood test data to predict biological age. Regardless if the blood was analyzed by Labcorp or Quest, higher levels of albumin (the left side of both images below) were associated with the greatest reduction in biological age, up to 5 years! In contrast, HbA1c was associated with a higher biological age when measured by Labcorp (top image, right side), and second to lead in the Quest analysis (bottom image, right side). Interestingly, glucose came in third and fifth in the Labcorb and Quest data sets, respectively, in terms of its positive association with biological age.

Glucose would’ve been an obvious choice, but would you have guessed that albumin may be just as important, and potentially more important for predicting biological age?

If you’re interested, please have a look at my book!

References

Earls JC, Rappaport N, Heath L, Wilmanski T, Magis AT, Schork NJ, Omenn GS, Lovejoy J, Hood L, Price ND. Multi-Omic Biological Age Estimation and Its Correlation With Wellness and Disease Phenotypes: A Longitudinal Study of 3,558 Individuals. J Gerontol A Biol Sci Med Sci. 2019 Nov 13;74(Supplement_1):S52-S60. doi: 10.1093/gerona/glz220.

Klemera P, Doubal S. A new approach to the concept and computation of biological age. Mech Ageing Dev. 2006;127:240–248. doi:10.1016/j. mad.2005.10.004

Levine ME, Lu AT, Quach A, Chen BH, Assimes TL, Bandinelli S, Hou L, Baccarelli AA, Stewart JD, Li Y, Whitsel EA, Wilson JG, Reiner AP, Aviv A, Lohman K, Liu Y, Ferrucci L, Horvath S. An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY). 2018 Apr 18;10(4):573-591. doi: 10.18632/aging.101414.

Mamoshina P, Kochetov K, Putin E, Cortese F, Aliper A, Lee WS, Ahn SM, Uhn L, Skjodt N, Kovalchuk O, Scheibye-Knudsen M, Zhavoronkov A. Population specific biomarkers of human aging: a big data study using South Korean, Canadian and Eastern European patient populations. J Gerontol A Biol Sci Med Sci. 2018 Jan 11.

1.7 Years of Biological Aging In The Past 3.6 Years

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In an earlier post (https://michaellustgarten.wordpress.com/2018/06/26/maximizing-health-and-lifespan-is-calorie-restriction-essential/), I documented my aging.ai biologic age for 13 blood test measurements from 2016 – 2019. If you missed that post, here are those data:
Note that note my average biologic age has slowly increased from 2016 to 2019, from 28y in 2016 (2 measurements), to 29.25y in 2017 (6 measurements), to 29.5y in 2018 (6 measurements), to 30y in my June 2019 measurement.

To gain more insight into my 2019 prediction for biologic age, I kept measuring. On September 17, 2019, I had my worst biological age to date, 33y, based on the blood test data below:

Seeing a biological age that high (for me) was the motivation that I needed to finally stick to a mild caloric restriction, which I hypothesized would positively affect my biological age. I wrote about this in my recent Phenotypic Age post (https://michaellustgarten.wordpress.com/2019/11/01/biological-age-31-3y-chronological-age-46y/). Did it work? Shown below is my blood test data for October 29th.

Based on that data, my biological age was 28y, and when averaging the 3 measurements in 2019 (so far!), my average biological age is 29.67y. When considering that my average biological age in 2016 was 28y, it looks like I’ve only aged ~1.7 years in 3.58 years of elapsed time!

If you’re interested, please have a look at my book!

Optimizing Biological Age: Is Calorie Restriction Essential?

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My goal is to break the world record for lifespan, 122 years, which is currently held by Jean Calment. How do I plan to do that? A good start would be calorie restriction (CR), a diet where you eat 10-30%+ less calories than your normal intake. CR is the gold standard for increasing lifespan in a variety of organisms, including yeast, flies, worms, and rodents (McDonald et al. 2010).

With the goal of maximizing my health and lifespan, in April 2015, I started a CR diet. Inherent in that was weighing all my food and recording it on an online website that tracks macro-and micro-nutrients. From then until March 2016, I was pretty good at keeping my calories relatively low, as I averaged 2302 calories. However, since 3/2016, it’s been exceedingly difficult to keep my calories that low, as I’ve averaged 2557 calories/day. So is having a higher calorie intake worse for my lifespan goal than a lower calorie intake?

Maybe not. In addition to tracking my daily nutrition since 2015, I’ve also had regular blood testing performed. I’ve measured the typical things that you get at a yearly checkup, including the lipid profile (triglycerides, total cholesterol, LDL, HDL, VLDL) markers of kidney and liver function (BUN, creatinine, uric acid, and ALT, AST, respectively), and the complete blood count (red and white blood cells, and their differentials). By tracking my daily nutrition and circulating biomarkers, I’m able to quickly intervene on any potential aging and disease-related mechanisms by using my diet to optimize my circulating biomarkers.

On my quest for optimal health and lifespan, biological age is more important than my chronological age (I’m 46y). So what’s my biological age? Between 2016-2019, the group at Insilico Medicine published 2 papers that included circulating biomarker data from more than 200,000 people (Putin et al. 2015, Mamoshina et al. 2018) to derive a biological age predictor (aging.ai). So what’s my biological age?

Shown below is my predicted biological age over 13 blood tests from 3/2016 to 6/2019:

Although I wasn’t on a CR diet during that time, my average biological age was 29.2 years, which is ~34% younger than my chronological age. Would my biological age be even younger with a lower calorie intake? I’m working on reducing my calorie intake again (it’s not easy for me), so stay tuned for that!

Here are the my biomarker values corresponding to each blood test, for anyone who wants to double check the results:

References

McDonald RB, Ramsey JJ. Honoring Clive McCay and 75 years of calorie restriction research. J Nutr. 2010 Jul;140(7):1205-10.

Putin E, Mamoshina P, Aliper A, Korzinkin M, Moskalev A, Kolosov A, Ostrovskiy A, Cantor C, Vijg J, Zhavoronkov A. Deep biomarkers of human aging: Application of deep neural networks to biomarker development. Aging (Albany NY). 2016 May;8(5):1021-33.

If you’re interested, please have a look at my book:

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