Variation Rhythms of Lymphocyte Subsets during Healthy Aging

Abstract

Immunological alterations associated with aging (immunosenescence) do not represent a simple unidirectional decline in all functions but develop as a complex remodeling of the immune system, involving multiple reorganization and developmentally regulated changes. In general, most data available about aging were obtained at particular age intervals and most of them come from Caucasian individuals from either Europe or the United States. Here, we report the frequencies of major lymphocyte subsets in healthy Brazilian individuals from 2 distinct geographic regions (Southeast and South) at several age intervals spanning a lifetime period (0–86 years). Overall, we demonstrated that changes in the frequencies of cells related to both innate and adaptive immunity clearly occur with aging in these individuals. These changes were not progressive and equally steady for all cell populations tested but instead showed an oscillatory or rhythmic behavior that was distinctive of each population at different age intervals. We also observed that abrupt changes in the frequencies of immune cells may occur in healthy individuals over 75 years old, suggesting there is an impaired flexibility of the immune system at late stages of life to sustain homeostasis via immune mechanisms. We presented reference ranges for healthy Brazilian individuals at all ages. The knowledge of these parameters in further detail will allow interventions to optimize immune function in advanced age and to improve the quality of life in the elderly.

Lifewide profile of cytokine production by innate and adaptive immune cells from Brazilian individuals

“…It is the first report describing changes in the profile of cytokine-producing leukocytes in Brazilian individuals within a large spectrum of age (0–85 years). These findings are an extension of another study from our group [34] that analyzed the frequency of sub-populations of leukocytes in Brazilian individuals at similar age range (0–85 years).…”

“…These cells showed a decreased production of TNF-α and IL-10 in adults and in the elderly group [12, 56, 57]. Our group has observed that frequencies of B-cells decline in Brazilian individuals of 19–40 age group and these data is compatible with the lower percentage of cytokine-positive B-cells in adulthood [34]. …”

“…A similar strategy was used previously by our group in a study analyzing rhythmic variations in the frequency of different subsets of peripheral blood monocytes in individuals from 0 to 86 years of age. These age groups were shown to represent a homogenous profile suitable to identify immunologically meaningful periods in life [34]. …”

“…This is particularly observed for CD4+ T-cells. In contrast, the frequency of CD8+ T-cells is well preserved during ageing declining only in individuals at 41–65 and 61–75 age ranges [34]. Results obtained by Alberti and coworkers [8] from the analysis of 47 European subjects at different ages indicated that the percentage of IFN-γ+-positive CD4+ T-cells significantly decreased in old and nonagenarian individuals in comparison with young subjects while the percentage of TNF-α-positive activated/memory CD4+ T-cells significantly decreased in old subjects in comparison with young ones.…”

“…Even among these reports, authors have observed variations and contrasting results as their samples vary demographically and geographically [34–36]. The study of various age groups should yield more meaningful data on immunosenescence that could be directly used by the geriatricians to restore or attenuate deregulated immune responses and assure a healthy longevity.…”