Tag Archives: Lymphocytes

Neutrophils, Lymphocytes, Monocytes: What’s Optimal For Health And Longevity?

White blood cells (WBCs) comprise many different cell types, including neutrophils, lymphocytes, monocytes, eosinophils, and basophils.

Neutrophils, lymphocytes, and monocytes account for ~99% of WBCs, and accordingly, in the video I propose optimal ranges for these cell types in terms of health and longevity.

Optimizing Biologic Age: Lymphocyte %

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 zincFASEB 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 womenExp 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 ageJ 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.

Circulating Biomarkers Associated With Coronary Artery Calcification

The coronary artery calcification (CAC) score is a measure of how much calcification is in the coronary arteries, and accordingly, is an in vivo measure of atherosclerosis. Why is the CAC score important? Besides its role in atherosclerosis, risk of death for all causes goes up at any age as the CAC score increases. For ex., in people younger than 50 (left side below), as the CAC score increases from 0 to 1-399, 400-999, and > 1000, risk of death for all causes increases by ~10-fold, from 2.3 per 1000 person years (PY) to 6.1/1000, 9.7/1000, and 22.7/1000. Similarly, for people older than 70y (right side below), as the CAC score increases, baseline all-cause mortality risk increases ~15-fold, from 5.6/1000 to 21.6/1000, 44.3/1000, and 76/1000, respectively (Hartaigh et al. 2016):

Screen Shot 2019-10-20 at 8.40.05 AM.png

Are blood biomarkers associated with CAC? When the CAC score was elevated, a greater percentage of white blood cells (WBCs) that were neutrophils and the red blood cell distribution width (RDW%) were higher, whereas lower CAC scores were associated with higher levels for the fraction of lymphocytes divided by total WBCs and higher total red blood cells (den Harder et al. 2018):

n l rdw cac

In agreement with these data, CAC scores > 100 were associated with a higher RDW% (13.0%) and a higher neutrophil/lymphocyte ratio (NLR; 1.54), when compared with CAC < 100 (RDW = 12.8%; NLR = 1.39; Gürel et al. 2019).

The findings that a higher RDW% and higher levels of neutrophils, but lower levels of lymphocytes are associated with a higher CAC score is in agreement with the data for how these variables change with aging and their associations with all-cause mortality risk. First, note that I previously reported that RDW% increases during aging and is associated with an increased risk of death from all causes (https://michaellustgarten.wordpress.com/2019/09/25/optimizing-biological-age-rdw/). Similarly, neutrophils increase, whereas lymphocytes decrease, thereby leading to a higher neutrophil/lymphocyte ratio during aging, which is associated with an increased all-cause mortality risk (https://michaellustgarten.wordpress.com/2019/10/10/neutrophil-lymphocyte-ratio-and-survival/).

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

References

den Harder AM, de Jong PA, de Groot MCH, Wolterink JM, Budde RPJ, Iŝgum I, van Solinge WW, Ten Berg MJ, Lutgens E, Veldhuis WB, Haitjema S, Hoefer IE, Leiner T. Commonly available hematological biomarkers are associated with the extent of coronary calcifications. Atherosclerosis. 2018 Aug;275:166-173. doi: 10.1016/j.atherosclerosis.2018.06.017.

Gürel OM, Demircelik MB, Bilgic MA, Yilmaz H, Yilmaz OC, Cakmak M, Eryonucu B. Association between Red Blood Cell Distribution Width and Coronary Artery Calcification in Patients Undergoing 64-Multidetector Computed TomographyKorean Circ J. 2015 Sep;45(5):372-7. doi: 10.4070/kcj.2015.45.5.372.

Hartaigh BÓ, Valenti V, Cho I, Schulman-Marcus J, Gransar H, Knapper J, Kelkar AA, Xie JX, Chang HJ, Shaw LJ, Callister TQ, Min JK. 15-Year prognostic utility of coronary artery calcium scoring for all-cause mortality in the elderly. Atherosclerosis. 2016 Mar;246:361-6. doi: 10.1016/j.atherosclerosis.2016.01.039.

Sarcopenia, Disease Risk, And The Neutrophil/Lymphocyte Ratio

In an earlier post, based on data from the Baltimore Longitidunal Study on Aging (BLSA), I suggested that total white blood cell (WBCs) counts between 3500 to 6000 cells per microliter of blood may be optimal for reducing disease risk and for maximizing longevity (https://michaellustgarten.wordpress.com/2015/08/13/blood-testing-whats-optimal-for-wbc-levels/).

However, within WBCs, neutrophils increase, whereas lymphocytes decrease during aging (Ruggiero et al. 2007, Starr and Dreary 2011). As a result, the ratio between neutrophils with lymphocytes (NLR) increases during aging from ~1.5 in 20 year olds to ~1.8 in adults older than 75y (Li et al. 2015):

Screen Shot 2019-10-06 at 3.40.06 PM

An increased neutrophil/lymphocyte ratio during aging may be bad for health and disease risk. First, a higher neutrophil/lymphocyte ratio is associated with sarcopenia (defined as the age-related loss of muscle mass and physical function) in older adults (average age, 72y; Öztürk et al. 2018):

Screen Shot 2019-09-13 at 7.46.06 AM

Second, risk of death for all causes is significantly increased for older adults (average age, 66y) that had higher NLR values (60-80%, >80%, equivalent to NLR = 1.92-2.41, > 2.41), when compared with lower NLR values (< 20%, 20-40%, 40-60%, equivalent to NLR < 1.90; Fest et al. 2019):

nlr

Similarly, all-cause mortality risk was 30% increased in older adults (average age, 54y) that had NLR values > 1.77, when compared with < 1.77, and 40% increased for NLR values > 2.15, when compared with < 2.15 (Kime et al. 2018).

What are my NLR values? Over 17 blood test measurements from 2015 – 2019, my average NLR is 1.11. So far so good!

nlr

 

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

 

References

Fest J, Ruiter TR, Groot Koerkamp B, Rizopoulos D, Ikram MA, van Eijck CHJ, Stricker BH. The neutrophil-to-lymphocyte ratio is associated with mortality in the general population: The Rotterdam Study. Eur J Epidemiol. 2019 May;34(5):463-470.

Kim S, Eliot M, Koestler DC, Wu WC, Kelsey KT. Association of Neutrophil-to-Lymphocyte Ratio With Mortality and Cardiovascular Disease in the Jackson Heart Study and Modification by the Duffy Antigen Variant. JAMA Cardiol. 2018 Jun 1;3(6):455-462. doi: 10.1001/jamacardio.2018.1042.

Li J, Chen Q, Luo X, Hong J, Pan K, Lin X, Liu X, Zhou L, Wang H, Xu Y, Li H, Duan C. Neutrophil-to-Lymphocyte Ratio Positively Correlates to Age in Healthy PopulationJ Clin Lab Anal. 2015 Nov;29(6):437-43. doi: 10.1002/jcla.21791.

Öztürk ZA, Kul S, Türkbeyler İH, Sayıner ZA, Abiyev A. Is increased neutrophil lymphocyte ratio remarking the inflammation in sarcopenia? Exp Gerontol. 2018 Sep;110:223-229.

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 AgingJ Am Coll Cardiol. 2007 May 8;49(18):1841-50.

Starr JM, Deary IJ. Sex differences in blood cell counts in the Lothian Birth Cohort 1921 between 79 and 87 years. Maturitas. 2011 Aug;69(4):373-6.