Researchers here suggest that infection plays an important role in cardiovascular disease in later life, and that the chronic inflammation of aging is a factor in allowing infection to cause significant harm to the heart. This is one of countless issues that could be mitigated through rejuvenation of the aging immune system, fixing the underlying issues that cause the immune system to become less functional and more inflammatory. These include atrophy of the thymus, the loss of thymic tissue where T cells of the adaptive immune system mature, loss of hematopoietic stem cell capacity, leading to reduced generation of new immune cells, the structural aging of lymph nodes, preventing immune cells from efficiently coordinating with one another, and the accumulation of senescent and otherwise dysfunctional immune cells.
Infection and infectious disease associated pathologies are often complicated by delays in immune response generation and excess inflammation that impact infection resolution. The term “inflammaging” was coined to denote the multifaceted dysregulation of homeostatic processes that over time culminates in quantifiable, organism-wide shifts towards inflammation in old age. As we shift our focus towards understanding the impact of inflammaging, we have recently determined that inflammaging may also accelerate the decline in cardiovascular fitness.
Age is a major prognostic factor for the development of non-tuberculous mycobacteria (NTM) disease, with recent clinical data reflecting increased incidence of NTM infection in elderly individuals. It is also known that tuberculosis (TB) caused by Mycobacterium tuberculosis (M.tb) can cause pericarditis, endocarditis, and myocarditis leading to sudden deaths. TB is a major global killer and it is estimated that 57% of all TB deaths globally occur in individuals older than 65. Based upon abundant circumstantial evidence, a direct link between mycobacterial infections, aging, and cardiac dysfunction was hypothesized by our group.
We examined how mycobacterial infection and inflammaging catalyze the decline in cardiovascular function in the elderly. Young (3 months) and old (18 month) female C57BL/6 mice were infected with a sub-lethal dose of Mycobacterium avium (M. avium), an NTM. We observed no differences in the M. avium bacterial numbers in the lung, liver, or spleen between young and old M. avium infected mice. However, through the course of M. avium infection, old mice developed severe dysrhythmia and developed pericarditis. Moreover, the hearts of M. avium infected old mice had increased cardiac hypertrophy, fibrosis, expression of pro-inflammatory genes, and infiltration of immune cells, which are hallmarks of myocarditis.
Since these cardiac abnormalities only manifested in old mice, we investigated several factors that contribute to this form of age dependent infectious myocarditis. Independent of M. avium infection, old mice had increased levels of pro-inflammatory cytokines in their serum, which may have predisposed old mice to infectious myocarditis. The reasons for increased inflammation in old age are multifaceted, and future studies will be needed to identify the principal sources of increased inflammation and whether ameliorating inflammation prevents NTM associated cardiac complications in old mice. This highlights how even low or what we may generally consider as insignificant bacterial loads can profoundly impact cardiovascular health.