The Gene Expression Patterns of Inflammaging and Immunosenescence in Cynomolgus Macaques

The aging of the immune system is an important contribution to frailty and age-related disease. Firstly the immune system becomes overactive, reacting to forms of the molecular damage of aging as though they were cancer, injury, or infection. Pathways evolved to be protective in youth instead become maladaptive in the damaged environment of aged tissue. The resulting constant inflammatory signaling is itself disruptive to tissue structure and function. This state is known as inflammaging.

Secondly, the immune system becomes progressively less able to coordinate its activities in order to attack and destroy pathogens and cancerous or senescent cells. Infections that a young person would shrug off can kill older individuals. Cancer is an age-related condition. Senescent cells accumulate to cause further harm rather than being promptly destroyed by immune cells. This loss of immune capabilities is known as immunosenescence.

In today's open access paper, researchers report on an assessment of immune aging in a non-human primate species. Cynomolgus macaques are commonly used in research, and are a much more relevant species than mice when it comes to examining the fine details of age-related changes in immune cell populations. Looking at gene expression, the researchers find examples of increased inflammatory activity in the innate immune system, aspects of inflammaging, versus evidence of specific losses of capacity in the adaptive immune system, aspects of immunosenescence.

Transcriptome analysis of cynomolgus macaques throughout their lifespan reveals age-related immune patterns

Alterations in the immune system are currently the subject of lively debate in aging research. The chronic low-grade inflammation caused by activation of innate immunity is a crucial phenomenon that occurs with aging and is globally known as "inflammaging". Additionally, impaired function of immunity changes in older individuals, known as "immunosenescence", prompt susceptibility to infectious or age-related diseases, damaging the overall biological system of the body and accelerating their biological age. Epigenetic factors have recently been regarded as mediators between aging and immune response.

We investigated the transcriptomic features of healthy and specific pathogen-free cynomolgus macaques (Macaca fascicularis). To explore whole lifespan, eight male macaques were divided into four age group each containing two individuals. As a laboratory animal, the macaques were protected from all environmental factors other than aging. Three years of this study revealed immune-related gene expression patterns.

The results showed recent findings of certain immune response and the age-associated network of primate immunity. Three important aging patterns were identified and each gene clusters represented a different immune response. The increased expression pattern was predominantly associated with innate immune cells, such as Neutrophils and NK cells, causing chronic inflammation with aging whereas the other two decreased patterns were associated with adaptive immunity, especially "B cell activation" affecting antibody diversity of aging. Furthermore, the hub gene network of the patterns reflected transcriptomic age and correlated with human illness status, aiding in future human disease prediction. Our macaque transcriptome profiling results offer systematic insights into the age-related immunological features of primates.

Comment Submission

Post a comment; thoughtful, considered opinions are valued. New comments can be edited for a few minutes following submission. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.