Age-Related Changes in the Clustering of Blood Populations in Cynomolgus Monkeys Depend on Sex and Immune Status

Abstract

Non-anthropoid primates cynomolgus monkeys (Macaca fascicularis), also known as crab-eating macaques, are increasingly used in biomedical and preclinical studies due to their evolutionary proximity to humans, sharing similar diets, infectious and senile diseases. Age-related changes and sexual dimorphism of the immune system of C. monkeys have not been sufficiently characterized in literature, though age and sex differences affect the course of diseases and sensitivity to medications. Aging in C. monkeys is accompanied by an increase in CD3+CD4+CD8+ (DP-T) cells, plasma B-cells, and a decrease in platelets. Erythromyeloid bias has also been noticed in older animals. There was an increase in eosinophils, haematocrit (HCT) and haemoglobin concentration (HGB). Senile decline in the function of the immune system had sex differences. An increase in the number of monocytes, cytotoxic lymphocytes (CTL) and a decrease in the T-helper population were more pronounced in older females. A significant reduction in the number of B-cells and activated T-cells was detected in males only. A moderate correlation with the regression model of aging was established for DP-T, HCT and HGB. The reduction in the B cells count in males and the increase in CTL level in females are moderately correlated with age. Other blood cell populations did not show significant correlations in the regression models due to their high sample variability. The novel cell population CD3-CD20loCD16/CD56+, presumably NK-cells subset, was revealed. This cell population demonstrated an increase trend with age in both sexes. Population-statistical age norms for different sexes for young and very old macaques were established. The blood population clusters associated with sex and immune status in older animals were also identified.

Age‐related changes in hematological biomarkers in common marmosets

“…Increasing granulocyte percent changes may be related to infection, cognitive disease, reactive oxygen species, and reactive nitrogen species (Horvath & Ritz, 2015; Martins Chaves et al, 2000). Increases in hematocrit, have been found to be associated with immune system function in aging primates (Karal‐ogly et al, 2023). Hematocrit, red blood cells, and hemoglobin are all related to immune system function and the ability to fight infection (Billett, 1990; Peter Klinken, 2002).…”

“…For many species, there are differences in these reference ranges associated with sex and age of the individuals. Thus, dividing the analyses by age, sex, and facility allows for a more complete understanding of how demographic factors change serum chemistry and complete blood count (CBC) parameters (Buchl & Howard, 1997; Chichester et al, 2015; Karal‐ogly et al, 2023; Kramer et al, 2022; Li et al, 2022). Healthy aging has been found to be associated with changes in hematology and clinical chemistry values (Johnson, 2006).…”

“…Previous papers which have examined marmoset serum chemistry and CBC in marmosets addressed very small numbers of animals that failed to accurately capture the range of health values for clinical parameters (McNees et al, 1982). Evaluations of serum chemistry and CBC values in other nonhuman primate species have revealed significant differences associated with age, sex, and often facility (Buchl & Howard, 1997; Chichester et al, 2015; Karal‐ogly et al, 2023; Kramer et al, 2022; Li et al, 2022). Given this, there is a need to further evaluate variance in value ranges that may be associated with factors such as age, sex, or the facility that the marmosets are housed in.…”

Hematopoietic Stem Cells and the Immune System in Development and Aging

“…In the elderly, an increase in platelets count has been observed in normal healthy aging in both humans and primates [ 227 , 228 ]. Due to the accumulation of platelets and other pathologies associated with vascular disorders, risk of thrombosis increases dramatically in the elderly [ 229 ].…”

Molecular Markers of Blood Cell Populations Can Help Estimate Aging of the Immune System

“…The authors discuss the contribution of gender factors to the longer life expectancy of women [ 14 ]. Sex differences in the aging of the primate immune system have also been observed [ 15 , 16 ].…”