Tag Archives: lifespan

Optimizing Biologic Age: Lymphocyte %

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The percentage of lymphocytes is one of the 9 blood test variables included in the biological age calculator, Phenotypic Age (https://michaellustgarten.wordpress.com/2019/09/09/quantifying-biological-age/). The reference range for lymphocyte % is 20 – 40% of the total amount of white blood cells (WBCs), but are higher or lower values optimal for health and longevity?

To answer that question, it’s important to know how levels of lymphocytes change during aging, and its association with risk of death for all causes. In one of the earliest studies to examine how the percentage of lymphocytes changes with age, Levine (2013) reported that lymphocyte % significantly decreased during aging in 9,389 adults (age range, 30 – 75y). However, the absolute values for these changes, i.e. from 40% to 30%, for ex., was not reported.

Similarly, lymphocyte % decreased during aging in a much larger study (377,686 subjects; age range, 18 – 85y; Wang et al. 2017):

Screen Shot 2019-11-16 at 9.38.37 AM

Interestingly, for women, lymphocyte % decreased from 27% to 21% from 20 – 35y, increased from 21% to 26% from 35 – 55y, then again decreased from 26% to 20% from 55y to 85y. In contrast, lymphocyte % more steadily decreased for men, from 28% to 17% from 20 – 85y.

Based on the aging data, higher values for lymphocyte % are are associated with biologic youth, whereas lower values are found in older adults. Although there are few studies that have investigated associations between lymphocyte % with aging or disease risk, in contrast, more studies have been published for absolute levels of lymphocytes.

In a small study of 106 older adults (> 85y) that were healthy (i.e. free of disease) at baseline, lymphocytes  less than 1.14*10^9 cells/L (equivalent to 1140*10^6 cells/L) was associated with an increased risk of death for all causes, when compared with 1850*10^6 cells/L (Izaks et al. 2003):

lympho mort

In a larger study (624 subjects), lymphocytes less than 1540*10^6 cells/L was associated with a significantly shorter average lifespan (~5y; 0.5 proportion remaining below), when compared with 1540 – 2040*10^6 cells/L . Also note that survival for the group that had 1540 – 2040*10^9 lymphocytes/L was not significantly different from the group that had more than 2040*10^9 lymphocytes/L (Leng et al. 2005):Screen Shot 2019-11-16 at 8.36.34 AM.png

In agreement with the smaller studies, lymphocytes < 1300 and < 1200*10^6 cells/L in women and men (red and blue, far left), respectively was associated with an increased all-cause mortality risk, when compared with average lymphocyte values ~1900*10^6 cells/L (decile 5) in a larger study that included 262,394 non-smokers (age range, 37 – 73y; Welsh et al. 2018):

Screen Shot 2019-10-08 at 7.26.51 AM

Collectively, these data suggest that higher values for lymphocyte % and for the absolute amount of lymphocytes may be optimal for minimizing disease risk and for maximizing longevity. If both are low, can they be raised? Circulating levels of lymphocytes are reduced during zinc deficiency (Fraker and King, 2001), so monitoring zinc intake, then increasing it to at least the RDA may be a first step towards increasing lymphocyte levels and %.

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

References

Fraker PJ, King LE. A distinct role for apoptosis in the changes in lymphopoiesis and myelopoiesis created by deficiencies in zinc. FASEB J. 2001 Dec;15(14):2572-8.

Izaks GJ, Remarque EJ, Becker SV, Westendorp RG. Lymphocyte count and mortality risk in older persons. The Leiden 85-Plus Study. J Am Geriatr Soc. 2003 Oct;51(10):1461-5.

Leng SX, Xue QL, Huang Y, Ferrucci L, Fried LP, Walston JD. Baseline total and specific differential white blood cell counts and 5-year all-cause mortality in community-dwelling older women. Exp Gerontol. 2005 Dec;40(12):982-7.

Levine ME. Modeling the rate of senescence: can estimated biological age predict mortality more accurately than chronological age? J Gerontol A Biol Sci Med Sci. 2013 Jun;68(6):667-74. doi: 10.1093/gerona/gls233.

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.

Welsh C, Welsh P, Mark PB, Celis-Morales CA, Lewsey J, Gray SR, Lyall DM, Iliodromiti S, Gill JMR, Pell J, Jhund PS, Sattar N. Association of Total and Differential Leukocyte Counts With Cardiovascular Disease and Mortality in the UK Biobank. Arterioscler Thromb Vasc Biol. 2018 Jun;38(6):1415-1423. doi: 10.1161/ATVBAHA.118.310945.

12-16 Years Younger Than My Chronological Age: What’s My Diet?

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My average biological age in 2019 is 12 years younger than my chronological age (46y) based on the Phenotypic Age calculator (https://michaellustgarten.wordpress.com/2019/11/01/biological-age-31-3y-chronological-age-46y/), and 16y younger based on aging.ai (https://michaellustgarten.wordpress.com/2019/11/04/years-of-biological-aging-in-the-past-4-years/). One factor that likely contributes to my relatively youthful biological age is my diet.

Shown below is my average daily dietary intake from January 1 through November 7th, 2019 (n=306 days). I weigh all of my food with a food scale, so these aren’t estimated amounts:

Screen Shot 2019-11-10 at 10.15.49 AM.png

In terms of weight (or volume), green tea is atop the list, as I drink 20 oz/day. Carrots come in second place (for why, see https://michaellustgarten.wordpress.com/2018/07/06/serum-albumin-and-acm/), followed by strawberries, red bell peppers, bananas, watermelon (for the lycopene), cauliflower, blueberries, blackberries, and raspberries. Note that I mix the bananas and berries in my green smoothies, which I drink 3-4x/week, which includes spinach (#11) and parsley (#23).

What does my average daily macro- and micro-nutrient data look like for 2019?

Screen Shot 2019-11-10 at 10.33.03 AM

Note that I purposefully have higher than the RDA values for several nutrients, including Vitamin C (see https://michaellustgarten.wordpress.com/2019/09/19/vitamin-c-dietary-intake-and-plasma-values-whats-optimal-for-health/), Vitamin K (see https://michaellustgarten.wordpress.com/2015/05/08/eat-more-green-leafy-vegetables-reduce-mortality-risk/), selenium (see https://michaellustgarten.wordpress.com/2015/05/28/selenium-dietary-intake-and-plasma-values-whats-optimal-for-health/), and others (see michaellustgarten.com).

In terms of supplements, I use 1000 IU of vitamin D from November – May, and I take a methylfolate-methylB12-B6 supplement, to help keep my homocysteine levels low.

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

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:
agingai2Note 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:
Screen Shot 2019-11-03 at 3.51.05 PM.png

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.

Screen Shot 2019-11-03 at 4.07.28 PM

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!

Biological Age = 31.3y, Chronological Age= 46y

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On June 10, 2019 (for the first time) I measured all of the blood test variables that are included in the biologic age calculator, Phenotypic Age, and ended up with a biological age = 35.39y (https://michaellustgarten.wordpress.com/2019/09/09/quantifying-biological-age/).

While that value is 23% younger than my chronological age (46y), I knew that I could do better! So I tried again on September 17, 2019. Basically, the same biological age, 35.58y:

pheno 8_2019.png

An 23% younger biological age on 2 separate dates, months apart might be good for most, but not for me. So, I tried again on October 29th, 2019, and voila, a biological age of 31.3y, which is 32% younger than my chronological age! How did I do it?

oct pheno.png

From my last blood test until my most recent blood test, I attempted a mild caloric restriction. To maintain my body weight, I require about 2800 calories per day, an amount which is based on daily body weight weighing in conjunction with daily dietary tracking. For the period of time that elapsed between my last 2 blood tests, I averaged 2657 calories/day, which is 3.2% less than the 2745 calories/day that I averaged for the dietary period that corresponded to my September blood test. That I was also in a very mild caloric restriction is confirmed by a reduction in my average body weight, which was (purposefully) down 0.7 lbs from September 17 to October 29th, when compared with the dietary period that corresponded to my September blood test (August 20 – September 17).

This is a superficial analysis of how I further reduced my biological age, but in future posts I’ll report the average dietary intake that corresponded to my relatively youthful biologic age!

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

Blood glucose: What’s optimal?

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The reference range for circulating levels of glucose is 70-130 mg/dL. That’s a wide range, so what’s optimal, especially considering that glucose is one of the variables used to quantify of biological age (https://michaellustgarten.wordpress.com/2019/09/09/quantifying-biological-age)?

In the largest study published for this subject (12,455,361 adults), risk of death for all causes was maximally reduced for glucose levels between 80-94 mg/dL (Yi et al. 2017). In contrast, mortality risk significantly increased when glucose levels were < 80 or > 100 mg/dL in both men and women:
bg

As glucose levels rise above 100 mg/dL, risk for Type II diabetes increases, which is one potential explanation for higher glucose levels being associated with a higher mortality risk. Why would glucose levels lower than 80 mg/dL also be associated with worse health? Interestingly, glucose levels < 80 mg/dL are associated with an increased risk of death from “total external causes” (left panel below), including unintentional accidents and transport accidents (middle, right panel below) in a relatively large study of 345,318 adults (Yi et al. 2019). In addition, an increased mortality risk from transport accidents involving pedestrians or cyclists was associated with glucose levels below 55 mg/dL (data not shown):

Screen Shot 2019-10-02 at 6.33.07 AM

Glucose levels increase during aging (Yi et al. 2017), evidence that adds further merit that lower is better (but not below 80 mg/dL!):

Screen Shot 2019-10-02 at 6.47.39 AM.png

What are my glucose levels? Shown below is my data for the past 13 years:

my bg

On the left side of the chart, I measured my glucose levels about once per year from 33-40y, resulting in an average value of 89 mg/dL. Since 2015 I started daily dietary tracking, and tested more often (19x), resulting in an average value of 87 mg/dL. The comparison between these 2 groups of data is not significantly different (p=0.19). Based on the data in Yi et al., my glucose levels should have increased from 92 to 96 mg/dL during the past 13 years. Instead, my glucose levels during that period are relatively stable, with average value (87.5 mg/dL) that would be expected for a 26y old. So far, so good!

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

 

References

Yi SW, Park S, Lee YH, Park HJ, Balkau B, Yi JJ. Association between fasting glucose and all-cause mortality according to sex and age: a prospective cohort study. Sci Rep. 2017 Aug 15;7(1):8194. doi: 10.1038/s41598-017-08498-6.

Yi SW, Won YJ, Yi JJ. Low normal fasting glucose and risk of accidental death in Korean adults: A prospective cohort study. Diabetes Metab. 2019 Jan;45(1):60-66. doi: 10.1016/j.diabet.2018.01.005.

Ending Aging-Related Diseases 2019: Lustgarten Presentation

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In the first half of this presentation, I talk about my contribution to the gut-muscle axis in older adults, and in the second half, my personalized approach to optimal health!

Also, here’s the article that corresponds to the presentation:
https://www.leafscience.org/the-gut-microbiome-affects-muscle-strength-in-older-adults/

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

Life Expectancy Increase (12-14 Years) With 5 Factors

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Following five lifestyle-related factors is associated with a gain in average life expectancy (Li et al. 2018). What are these factors? Not smoking, having a BMI between 18.5 to 24.9 kg/m2, engaging in more than 30 minutes of moderate to vigorous physical activity (at a minimum, walking ~3 miles per hour; 30 minutes of that = 1.5 miles of walking per day), moderate alcohol intake (5 to 15 g/d for women and 5 to 30 g/d for men), and a high diet quality score.

Starting at age 50y, having all 5 of these factors was associated with a life expectancy of an additional 43.1 years for women, and 37.6 years for men, which is an increase in average life expectancy of 14 years for women and 12 years for men, respectively:

Screen Shot 2019-09-29 at 12.49.55 PM.png

Quantifying whether or not you have the first 4 factors is easy, but what qualifies as having a high dietary score? The alternative healthy eating index (AHEI; McCullough et al. 2002) was used to define the dietary score. An AHEI score of more than 43.5 in women and 50 in men qualifies as having a high dietary quality. How is the AHEI defined?

If you eat more than 5 servings of vegetables (1 serving = ~3 ounces, or 80g) per day, you get 10 points. Similarly, more than 4 servings of fruit gets you 10 points. If you eat 1 serving (= 1.5 ounces, or 42 grams) of nuts and or soy protein (tofu) you get 10 points. If your intake of white meat (including fish, poultry) divided by red meat is greater than 4, you get 10 points. If you eat > 9 grams of cereal fiber (not 9 grams of grains, but the actual fiber content) per day, you get 10 points. For example, 9 grams of cereal fiber corresponds to 90g/day of dry oats. Alcohol is also included within the AHEI: if you have 1.5 – 2.5 servings of alcoholic drinks per day (for men) or 0.5 – 1.5 servings/day for women, that’s 10 points. Zero points would be not consuming alcoholic drinks, or > 3.5 drinks for men, and > 2.5 drinks per day for women. Having a polyunsaturated/saturated fat (P:S) intake > 0.5 yields 8 points, whereas a ratio > 0.7 yields 10 points. Consuming < 0.9 grams of trans fat per day yields 10 points, and finally, using a multivitamin for more than 5 years yields 10 points. To determine your score, have a a look at the median AHEI values reported for men:

Screen Shot 2019-09-29 at 10.11.15 AM

And for women:

Screen Shot 2019-09-29 at 10.13.37 AM.png

How many of the 5 factors do I have? I don’t smoke, my BMI is within the BMI range (my body weight was 158 this morning, so barely!), and I easily walk more than an hour/day + 3-4 days of exercise/week, so I qualify for the first 3 factors. However, I rarely drink alcohol, so I don’t qualify for that factor. What about the diet quality factor? To determine that, I’ll need to calculate if I have more than 50 AHEI points.

For the AHEI index, getting 5, 4, and 1 servings of veggies, fruit, and nuts per day is easy for me, so I’ve got 30 points so far. I eat oats once or twice/week, but not enough to get 9g of cereal fiber/day, so 0 points there. I eat 80 grams of sardines every day (560 grams/week), and ~150 grams of red meat per week, for a ratio of 3.7. That wouldn’t qualify me for 10 points, but 8 instead (see Quintile 4), where the white/red meat ratio would need to be higher than 2.5. I rarely drink alcohol, so 0 points for me there. Using last week’s dietary data, my P:S ratio is about 0.5, and my trans fat intake (almost exclusively from full-fat dairy) is 0.7 g/day, so I get 8 points and 10 points, respectively. In terms of multivitamin use, I only supplement with Vitamin D in the winter, and with a methylfolate-methylcobalamin-B6 stack (to reduce my homocysteine by ~10%). I haven’t been supplementing with that stack for more than five years, so I get a 0 there. Nonetheless, my score is 56 points, which would qualify me as having a high diet quality score.

Collectively, I have 4 of the 5 lifestyle factors that are associated with an increase in life expectancy. Based on the data from Li et al., my average life expectancy would be 85.4y. Adding in moderate alcohol intake would give me all 5 factors, and would result in a life expectancy gain of an additional 2.2 years. I’ve included 1-2 glasses of wine in my diet in the past, but it had no effect on my HDL or other circulating biomarkers, so I removed it. For me, the risk related to alcohol intake may not be worth the gain in life expectancy. Also note that these are average, population-based values, and I expect an additional gain in life expectancy gain because of my continuous quest for biological age optimization (https://michaellustgarten.wordpress.com/2019/09/09/quantifying-biological-age_!

References

Li Y, Pan A, Wang DD, Liu X, Dhana K, Franco OH, Kaptoge S, Di Angelantonio E, Stampfer M, Willett WC, Hu FB. Impact of Healthy Lifestyle Factors on Life Expectancies in the US Population. Circulation. 2018 Jul 24;138(4):345-355. doi: 10.1161/CIRCULATIONAHA.117.032047.

McCullough ML, Feskanich D, Stampfer MJ, Giovannucci EL, Rimm EB, Hu FB, Spiegelman D, Hunter DJ, Colditz GA, Willett WC. Diet quality and major chronic disease risk in men and women: moving toward improved dietary guidance. Am J Clin Nutr. 2002 Dec;76(6):1261-71.

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

Drink Green Tea, Reduce All-Cause Mortality Risk?

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Is green tea consumption associated with reduced risk of death risk from all causes? To investigate this question, Tang et al. (2015) performed a meta-analysis of 5 studies, including 200,884 subjects. As shown below, drinking 2-3 cups (16-24 oz.) of green tea per day was associated with maximally decreased all-cause mortality risk, ~10%.

green tea

Post update (9/15/2019): Is there new data since this post was first published (2015) for the association between green tea with all-cause mortality risk? Two relatively large studies have been published since then. First, in a study of 164,681 men (average age, ~53y), consuming green tea (~15g/day) was associated with a maximally reduced risk of death from all causes (black lines; Liu et al. 2016). However, note that this data included both smokers and non-smokers. For non-smokers (green lines), all-cause mortality risk was maximally reduced even further at smaller doses, including ~ 6-10g of green tea/day:

Screen Shot 2019-09-15 at 9.15.09 AM

In support of these data, never-smoking men and women (average age, ~52y) that drank more than  8.2g, and 3.3g, respectively, of green tea had an 11% reduced risk of all-cause mortality in Zhao et al. (2017).

The data is clear, drink green tea!

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

Reference

Liu J, Liu S, Zhou H, Hanson T, Yang L, Chen Z, Zhou M. Association of green tea consumption with mortality from all-cause, cardiovascular disease and cancer in a Chinese cohort of 165,000 adult men. Eur J Epidemiol. 2016 Sep;31(9):853-65.

Tang J, Zheng JS, Fang L, Jin Y, Cai W, Li D. Tea consumption and mortality of all cancers, CVD and all causes: a meta-analysis of eighteen prospective cohort studies. Br J Nutr. 2015 Jul 23:1-11.

Zhao LG, Li HL, Sun JW, Yang Y, Ma X, Shu XO, Zheng W, Xiang YB. Green tea consumption and cause-specific mortality: Results from two prospective cohort studies in China. J Epidemiol. 2017 Jan;27(1):36-41.

Quantifying Biological Age

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In an earlier post, I wrote about quantifying my biological age with aging.ai (https://michaellustgarten.wordpress.com/2018/06/26/maximizing-health-and-lifespan-is-calorie-restriction-essential/). The importance of that post is illustrated by the finding that based on data from 13 blood tests between 2016 – 2019, my average biological age is 29.2y, which is ~33% younger than my chronological age.

On my quest for optimal health, I’m striving to get as accurate as possible when it comes to quantifying biological age. While the aging.ai biomarker set is strongly correlated with biologic age (r = 0.80), in 2018 two papers were published (Liu et al., Levine et al.) that introduced “Phenotypic Age”, which includes a combination of 9 circulating biomarkers + chronological age that is better at predicting biological age (r = 0.94) than aging.ai. It includes analytes that are found on the standard blood chemistry screen, including albumin, creatinine, glucose, lymphocyte %, mean corpuscular volume (MCV), red blood cell distribution width (RDW), alkaline phosphatase, white blood cells, and an analyte that is not found on that panel, C-reactive protein (CRP). In addition, chronological age is included as a covariate.

So what’s my biological age based on the Phenotypic Age calculator? When I input my data from my latest blood test measurement on 6/4/2019, I get a biological age of 35.39y, which is 23% lower than my chronological age of 46. Not bad!

phenoage

To quantify your biological age with the Phenotypic Age calculator, input your data in the Excel file that is embedded within the first paragraph of the following link:

DNAmPhenoAge_gen

3.27.25 Edit: In the link above, note that the denominator in D17 should be 0.090165, not 0.09165. Additionally, the units for albumin should be g/dL (not mg/dL), and lymphocyte isn’t spelled correctly. I can’t upload a new link-I’d have to upgrade my WordPress account to be able to upload files (which is ridiculous!).

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

References

Liu Z, Kuo PL, Horvath S, Crimmins E, Ferrucci L, Levine M. A new aging measure captures morbidity and mortality riskacross diverse subpopulations from NHANES IV: A cohort study. PLoS Med. 2018 Dec 31;15(12):e1002718. doi: 10.1371/journal.pmed.1002718.

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.