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.