Improving immunity in the elderly: current and future lessons from nonhuman primate models

Abstract

The immune system must overcome daily challenges from pathogens to protect the body from infection. The success of the immune response to infection relies on the ability to sense and evaluate microbial threats and organize their elimination, while limiting damage to host tissues. This delicate balance is achieved through coordinated action of the innate and adaptive arms of the immune system. Aging results in several structural and functional changes in the immune system, often described under the umbrella term "immune senescence". Age-related changes affect both the innate and adaptive arms of the immune system and are believed to result in increased susceptibility and severity of infectious diseases, which is further exacerbated by reduced vaccine efficacy in the elderly. Therefore, multiple strategies to improve immune function in the aged are being investigated. Traditionally, studies on immune senescence are conducted using inbred specific pathogen free (SPF) rodents. This animal model has provided invaluable insight into the mechanisms of aging. However, the limited genetic heterogeneity and the SPF status of this model restrict the successful transfer of immunological discoveries between murine models and the clinical setting. More recently, nonhuman primates (NHPs) have emerged as a leading translational model to investigate immune senescence and to test interventions aimed at delaying/reversing agerelated changes in immune function. In this article, we review and summarize advances in immunorestorative approaches investigated in the NHP model system and discuss where the NHP model can support the development of novel therapeutics.

The aging common marmoset's immune system: From junior to senior

“…One important aspect of immunosenescence in humans and rhesus macaques are changes of the T cell compartment. CD4 + T cell numbers decline with age, while CD8 T cell numbers increase resulting in a decrease of the CD4/CD8 T cell ratio (Meyer et al, 2012; Zheng et al, 2014). The diminished naïve T cell pool in the elderly is most likely a consequence of both thymic involution and chronic antigenic stimulation (Ventura, Casciaro, Gangemi, & Buquicchio, 2017).…”

“…In this context, the immune system plays an important role by influencing wellbeing, healthy aging, and the development of age‐associated diseases in different ways. Various immunological changes coincide with aging—often described as immunosenescence: especially alterations in the T cell department, for example, loss of naïve cells, increase of exhausted cells, and the appearance of “inflammaging,” an increase of inflammatory cytokines (Meyer, Kerns, Haberthur, & Messaoudi, 2012; Zheng, Zhang, Pang, & Zheng, 2014), seem to contribute to the age‐dependent decline of immune function. All these changes likely lead to increased susceptibility to infections, reduced immune response to vaccines, or the occurrence of autoimmune diseases.…”

Immunosenescence: the potential role of myeloid-derived suppressor cells (MDSC) in age-related immune deficiency

“…It is important to understand whether the inhibition of MDSCs function in aged mammals could reverse immunosenescence and thus provide insight into the origin of immunosenescence. As far as we know, this approach has not been utilized in studies attempting to find ways to rejuvenate the immune system of elderly people or primates [ 233 , 234 ]. Inhibiting the functions of MDSCs and other immunosuppressive regulators could provide the target to reverse the process of immunosenescence (i.e., induce rejuvenation), using the same approach which improves the immune surveillance of tumors and infections.…”

Contributions of Nonhuman Primates to Research on Aging

“…It is still difficult, however, to specifically define the effects of shifting levels of cytokines, chemokines, and other circulating factors on biological versus chronological aging outcomes among individuals (ie, as measures of healthy vs less healthy aging). 10,66,152 …”