Discussed in the video:
What’s my biological age on blood test #6 in 2020?
What’s my average biological age for 2020, and how does it compare with 2019?
Are there links between calorie intake, cardiovascular fitness (RHR, HRV), and diet composition with my biological age?
Maximal lifespan in calorie restricted (CR) mice can range from 45 – 55 months. In this video, I present data for 3 studies on rapamycin-can it beat CR for maximal lifespan?
NR and NMN are popular ways to try to boost levels of NAD+, but that approach hasn’t worked every time in human studies. One reason for that may involve CD38, which degrades both NR and NMN. With the goal of boosting NAD+ levels during aging, why does CD38 increase with age, and what can be done about it? All that and more in this video!
Circulating levels of white blood cells (WBCs) are one of the 10 variables used to quantify biological age with PhenoAge (https://atomic-temporary-71218033.wpcomstaging.com/2019/09/09/quantifying-biological-age). The reference range for WBCs is 4.5 – 11 *10^9 cells/L, but within that range, what’s optimal?
Several studies have reported that WBCs greater than 5 are associated with an increased all-cause mortality risk (Ahmadi-Abhari et al. 2013, Samet et al. 2005, Weijenberg et al. 1996). While observational studies are important for identifying associations with mortality risk, stronger evidence is obtained when the data from the same subjects are tracked for a long time period. Perhaps the best evidence for the association between WBCs with mortality risk comes from the Baltimore Longitudinal Study on Aging (BLSA), which studied 2803 men and women over a period of 44 years (Ruggiero et al. 2007). As shown below, subjects that had circulating WBCs between 3.5 – 6 had the best survival, whereas WBCs below 3.5, between 6 – 10, and 10+ each had successively higher risk. The 0.5 point on the y-axis of the curve (survival) is defined as 50% mortality, and is the point where half of the study subjects died, whereas the remaining 50% were still alive. At that point, compared with subjects that had WBCs between 6 – 10, people that had WBCs between 3.5 – 6 lived ~7 years longer! So getting your WBC into that range may be a big deal for increasing life expectancy.
How can you reduce circulating WBCs? One way to reduce WBCs is to eat less calories, thereby reducing your body weight. As shown below, eating less calories resulted in a decreased BMI and decreased WBCs in the Biosphere II project (Walford et al. 2002), almost exactly in the same pattern:
Because calorie restriction reduced WBCs from ~6.8 to 4.6, should 4.6 be considered optimal? In support of this idea, calorie restriction is well documented to increase lifespan in a variety of organisms, including flies, worms, and rodents. Although there isn’t any evidence (yet) on the long-term effects of calorie restriction (CR) on lifespan in people, it has been shown to be protective against age-related diseases, including abdominal obesity, diabetes, hypertension, and cardiovascular disease (Omodei and Fontana 2011). Therefore, a reduced WBC level may be related to the positive health-related effects of CR.
As an argument against using the CR-mediated reduction in WBC as a guide for what the optimal range should be, calorically-restricted mice have a decreased survival in response to infection (Goldberg et al. 2015):
However, it’s important to note that infection-related survival was decreased in CR mice that were 40% restricted in terms of daily calories. Based on the Biosphere 2 data above, BMI was reduced from ~23 to 19, which translates into a 17% reduction. However, whether 17% CR is better for improving infection-related survival compared with 40% CR is currently unknown.
What’s my WBC level? Shown below is my WBC data for the past 16 years, including 25 measurements (average WBCs, 4.78 * 10^9 cells/L). The 2 red lines delineate the 3.5 – 6 range that was associated with an increased lifespan in the BLSA study (Ruggiero et al. 2007), and based on that, I’ve only had 1 measurement that was higher than that range.
Starting from the red arrow below, WBCs increase during the 22-year period that precedes death (Ruggiero et al. 2007), so making sure that they don’t go up during aging is important!
If you’re interested, please have a look at my book!
References
Ahmadi-Abhari S, Luben RN, Wareham NJ, Khaw KT. Seventeen year risk of all-cause and cause-specific mortality associated with C-reactive protein, fibrinogen and leukocyte count in men and women: the EPIC-Norfolk study. Eur J Epidemiol. 2013 Jul;28(7):541-50.
Goldberg EL, Romero-Aleshire MJ, Renkema KR, Ventevogel MS, Chew WM, Uhrlaub JL, Smithey MJ, Limesand KH, Sempowski GD, Brooks HL, Nikolich-Žugich J. Lifespan-extending caloric restriction or mTOR inhibition impair adaptive immunity of old mice by distinct mechanisms. Aging Cell. 2015 Feb;14(1):130-8.
Jee SH, Park JY, Kim HS, Lee TY, Samet JM. White blood cell count and risk for all-cause, cardiovascular, and cancer mortality in a cohort of Koreans. Am J Epidemiol. 2005 Dec 1;162(11):1062-9.
Omodei D, Fontana L. Calorie restriction and prevention of age-associated chronic disease. FEBS Lett. 2011 Jun 6;585(11):1537-42.
Ruggiero C, Metter EJ, Cherubini A, Maggio M, Sen R, Najjar SS, Windham GB, Ble A, Senin U, Ferrucci L. White blood cell count and mortality in the Baltimore Longitudinal Study of Aging. J Am Coll Cardiol. 2007 May 8;49(18):1841-50.
Walford RL, Mock D, Verdery R, MacCallum T. Calorie restriction in biosphere 2: alterations in physiologic, hematologic, hormonal, and biochemical parameters in humans restricted for a 2-year period. J Gerontol A Biol Sci Med Sci. 2002 Jun;57(6):B211-24.
Weijenberg MP, Feskens EJ, Kromhout D. White blood cell count and the risk of coronary heart disease and all-cause mortality in elderly men. Arterioscler Thromb Vasc Biol. 1996 Apr;16(4):499-503.
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
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.
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:
If you’re interested, please have a look at my book!
Video of my presentation starts at 14:28, and lasts until 1:29:00+!
If you’re interested, please have a look at my book!
If you’re interested, please have a look at my book!
With the goal of improving health and extending lifespan, Roy Walford was a pioneer in terms of studying (and implementing) a diet that is calorie restricted but that also contains optimal nutrition (CRON). Unfortunately, Walford died at age 80 from complications related to Amyotrophic Lateral Sclerosis (ALS). Were there any factors in his nutritional approach that increased his risk for developing ALS?
On Walford’s website, http://www.walford.com, he listed 2 sample days of both food intake and his resulting macro- and micronutrient composition:
Although several micronutrients (calcium, sodium, zinc) are below the RDA on day 1, Walford’s 2-day average bring these values close to the RDA. However, his Vitamin E intake on day 1 and day 2 (shown below) are glaringly deficient. On day 1, his Vitamin E intake was only 2.8 mg. On day 2, it was 6.1 mg, for a 2-day average value of 4.5 mg. The RDA for Vitamin E was updated in 2000 (Food and Nutrition Board, 2000) from 8 mg to the current 15 mg-he wasn’t close to either value!
Dietary Vitamin E has been reported to be decreased in patients with ALS, when compared with ALS-free controls, as shown below (Veldink et al. 2007). Although the subjects of Veldink et al. had an increased calorie intake when compared with Walford (2842 and 2938 calories in controls and in ALS patients, respectively), when scaled down to Roy’s 1500 calorie intake, a dietary Vitamin E intake of 9 mg would be found in ALS patients, with 10.8 mg found in the controls. For comparison, Walford’s 2-day Vitamin E intake was only 6.1 mg! Interestingly, the only other dietary nutrient category that was significantly different between ALS patients and controls was polyunsaturated fat (PUFA) intake, which was also low (8.8g) in Walford’s 2-day diet.
I’m not at all saying that Walford’s dietary deficiencies in Vitamin E and PUFA caused his ALS. It’s also unknown whether the 2 days that he posted on his website are representative of his overall CRON approach. But it’s an interesting observation, isn’t it?
If you’re interested, please have a look at my book!
https://www.amazon.com/dp/B01G48A88A?ref_=k4w_oembed_omIChDjq2EkggX&tag=kpembed-20&linkCode=kpd
References
Food and Nutrition Board, Institute of Medicine. Vitamin E. Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. Washington, D.C.: National Academy Press; 2000:186-283.
Freedman MD, Kuncl RW, Weinstein SJ, Malila N, Virtamo J, Albanes D. Vitamin E serum levels and controlled supplementation and risk of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2013 May;14(4):246-51
Veldink JH, Kalmijn S, Groeneveld GJ, Wunderink W, Koster A, de Vries JH, van der Luyt J, Wokke JH, Van den Berg LH. Intake of polyunsaturated fatty acids and vitamin E reduces the risk of developing amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2007 Apr;78(4):367-71.
My approach towards optimal health involves yearly blood testing and tracking my results to catch changes before they become problematic. In this article, I will evaluate the published literature to propose an optimal range for circulating white blood cells (WBC).
Why is measuring WBCs important? Briefly, circulating WBCs are correlated with inflammation- inflammation increases during aging, is associated with decreased function of multiple organ systems, and is associated with an increased chronic disease risk (Cevenini et al. 2013).
As shown below, Huang et al. (2007) reported significant correlations between circulating WBCs with a marker of inflammation, C-reactive protein (CRP). This correlation was statistically significant in the whole population (14,114 subjects), in subjects older than or less than 50 years, and separately in men and women.
Based on that data, Huang et al. (2007) suggested changing the reference range (8 years ago!) for WBCs from 4-11 to 3.11-8.83 K/mm3. But within that range, what’s optimal for health and longevity? Because WBC are elevated in association with inflammation, the hypothesis would be that the lower end of the range is better, with values ~4 being optimal. Is this true?
Several studies have reported that WBC values greater than 5 are associated with an increased all-cause mortality risk (Ahmadi-Abhari et al. 2013, Samet et al. 2005, Weijenberg et al. 1996). However, the best evidence for the association between WBCs with mortality risk comes from the Baltimore Longitudinal Study on Aging (BLSA), which studied 2803 men and women over a period of 44 years (Ruggiero et al. 2007). As shown below, subjects that had circulating WBC between 3.5 and 6 had decreased mortality risk, whereas below 3.5, between 6-10, and 10+ each had successively higher risk. The 0.5 point on the y-axis of the curve (survival) is defined as 50% mortality, where half of the study subjects have died. At that point, compared with subjects with WBC values between 6-10, people with values between 3.5 and 6 live ~7 years longer! So getting your WBC into that range may be a big deal for living significantly longer.
How can you reduce circulating WBCs? One way to reduce WBCs is to eat less calories, thereby reducing your body weight. As shown below, eating less calories resulted in decreased BMI and decreased WBCs in the Biosphere II project (Walford et al. 2002), almost exactly in the same pattern:
Because calorie restriction reduced WBCs from ~6.8 to 4.6, should 4.6 be considered optimal? In support of this idea, calorie restriction is well documented to increase lifespan in a variety of organisms, including flies, worms, and rodents. Although there isn’t any evidence on the long-term effects of calorie restriction (CR) on lifespan in people, it has been shown to be protective against age-related diseases, including abdominal obesity, diabetes, hypertension, and cardiovascular disease (Omodei and Fontana 2011). Therefore, a reduced WBC level may be related to the positive health-related effects of CR.
As an argument against using the CR-mediated reduction in WBC as a guide for what the optimal range should be, calorically restricted mice have decreased infection-related survival (Goldberg et al. 2015):
However, it’s important to note that infection-related survival was decreased in adult CR mice that were 40% restricted in terms of daily calories. Based on the Biosphere 2 data above, BMI was reduced from ~23 to 19, which translates into an ~18% reduction in BMI. However, whether 18% CR is better for improving infection-related survival compared with 40% CR is currently unknown.
What’s my WBC level? My lowest WBC value was in 2008, at 3.9. In 4 measurements from 2008-2013 my WBC increased to 4.4, 4.6, 5.7, and 5.9. However, in my most recent blood test, they’re back down to 4.4. I have 2 possible explanations for reducing my age-related increase in WBCs. First, my body weight weight is ~10 lbs less since last year, and my 100g+ fiber diet may improve gut barrier function to keep bacteria and other stuff out of my blood that shouldn’t be there, thereby decreasing my systemic immune response.
My recent 4.4 WBC value puts me close to the CR-value (4.6), and within the optimal 3.5-6 range identified in the BLSA study. So far so good! Stay tuned for the data next year to see if my WBCs remain low or start to rise again.
If you’re interested, please have a look at my book!
References
Ahmadi-Abhari S, Luben RN, Wareham NJ, Khaw KT. Seventeen year risk of all-cause and cause-specific mortality associated with C-reactive protein, fibrinogen and leukocyte count in men and women: the EPIC-Norfolk study. Eur J Epidemiol. 2013 Jul;28(7):541-50.
Cevenini E, Caruso C, Candore G, Capri M, Nuzzo D, Duro G, Rizzo C, Colonna-Romano G, Lio D, Di Carlo D, Palmas MG, Scurti M, Pini E, Franceschi C, Vasto S. Age-related inflammation: the contribution of different organs, tissues and systems. How to face it for therapeutic approaches. Curr Pharm Des. 2010;16(6):609-18.
Goldberg EL, Romero-Aleshire MJ, Renkema KR, Ventevogel MS, Chew WM, Uhrlaub JL, Smithey MJ, Limesand KH, Sempowski GD, Brooks HL, Nikolich-Žugich J. Lifespan-extending caloric restriction or mTOR inhibition impair adaptive immunity of old mice by distinct mechanisms. Aging Cell. 2015 Feb;14(1):130-8.
Huang ZS, Lo SC, Tsay W, Hsu KL, Chiang FT. Revision in referene ranges of peripheral total leukocyte count and differential leukocyte percentages based on a normal serum C-reactive protein level. J Formos Med Assoc. 2007 Aug;106(8):608-16.
Jee SH, Park JY, Kim HS, Lee TY, Samet JM. White blood cell count and risk for all-cause, cardiovascular, and cancer mortality in a cohort of Koreans. Am J Epidemiol. 2005 Dec 1;162(11):1062-9.
Omodei D, Fontana L. Calorie restriction and prevention of age-associated chronic disease. FEBS Lett. 2011 Jun 6;585(11):1537-42.
Ruggiero C, Metter EJ, Cherubini A, Maggio M, Sen R, Najjar SS, Windham GB, Ble A, Senin U, Ferrucci L. White blood cell count and mortality in the Baltimore Longitudinal Study of Aging. J Am Coll Cardiol. 2007 May 8;49(18):1841-50.
Walford RL, Mock D, Verdery R, MacCallum T. Calorie restriction in biosphere 2: alterations in physiologic, hematologic, hormonal, and biochemical parameters in humans restricted for a 2-year period. J Gerontol A Biol Sci Med Sci. 2002 Jun;57(6):B211-24.
Weijenberg MP, Feskens EJ, Kromhout D. White blood cell count and the risk of coronary heart disease and all-cause mortality in elderly men. Arterioscler Thromb Vasc Biol. 1996 Apr;16(4):499-503.
Michael Lustgarten 