This open access paper reviews the interactions between cellular senescence, autophagy, and immunosenescence, with chronic infection as a mediating mechanism. Given the present state of knowledge and biotechnology, it is challenging enough to look at any two aspects of the aging body and consider how they might interact in isolation, but this can only ever be a thin slice of the bigger picture. All systems and states in our biochemistry interact with one another in some way, directly or indirectly, and examining ever larger sets of relationships between greater numbers of systems and states is the path to greater understanding of aging as a phenomenon. It is also somewhat beyond present capabilities, a complex, challenging endeavor for the scientists of future decades, which is why bypassing the need for this sort of understanding is highly desirable when working towards therapies to treat aging. We cannot afford to wait for a near complete knowledge of the progression of aging.

The state of cellular senescence, in which replication is shut down, can be a reaction to damage. It is one of the ways in which cancer risk is sufficiently minimized to allow higher forms of multicellular life to exist. Senescent cells are unfortunately harmful to surrounding tissues, and their accumulation with age is one of the root causes of degenerative aging. Autophagy is a collection of cellular damage control processes, responsible for recycling broken and unwanted proteins or structures in the cell. Loss of autophagy to the point of excessive accumulation of molecular damage is one way for cells to become senescent, and unfortunately autophagy declines with age. Immunosenescence is the aged state of the immune system, characterized by chronic inflammation and incapacity. In later life, the immune system becomes far less effective in removing damaged cells, such as senescent cells, as well as less effective when it comes to a defense against invading pathogens.

Even when simply considering just these three line items, the potential interactions are complex and challenging to rigorously prove. The authors of this paper advance the common view that chronic infection impairs autophagy, and thus in turn generates increased numbers of senescent cells, which accelerates the progression of immunosenescence.

Chronic Infections: A Possible Scenario for Autophagy and Senescence Cross-Talk