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

Abstract

Multiple tissues and systems in the organism undergo modifications during aging due to an accumulation of damaged proteins, lipids, and genetic material. To counteract this process, the cells are equipped with specific mechanisms, such as autophagy and senescence. Particularly, the immune system undergoes a process called immunosenescence, giving rise to a chronic inflammatory status of the organism, with a decreased ability to counteract antigens. The obvious result of this process is a reduced defence capacity. Currently, there is evidence that some pathogens are able to accelerate the immunosenescence process for their own benefit. Although to date numerous reports show the autophagy⁻senescence relationship, or the connection between pathogens with autophagy or senescence, the link between the three actors remains unexplored. In this review, we have summarized current knowledge about important issues related to aging, senescence, and autophagy.

Keywords: aging; autophagy; chronic infections; immune system; immunosenescence; pathogens; senescence.

Figure 1

Different stages of cell damage. Autophagy is one of the mechanisms acting as the first barrier against cell damage to avoid the accumulation of non-functional organelles or proteins in the cells. When this mechanism is overburdened, apoptosis or senescence is activated. These mechanisms stop the damaged cells’ dissemination and prevent the apparition of age-related diseases, such as neurodegenerative disorders or cancer. An accumulation of damaged organelles and proteins and changes in the genetic material are observed in these diseases.

Figure 2

Autophagy has a dual role in senescence activation. There are several factors that stimulate senescence activation. These includes ROS accumulation, hypoxia DNA damage, or telomere shortening. Once activated, senescent cells undergo morphological and functional modifications, which include arrest of proliferation, the resistance to apoptotic signals, size increasing, alteration in gene expression, and activation of SASP. The autophagic pathway could prevent senescence due to its capacity to eliminate potentially dangerous elements generated in aging, such as damaged organelles and proteins; and by collaborating in genome stability. Nevertheless, when senescence is activated, autophagy plays a positive role by autophagic degradation of p53 inhibitors or by increasing the levels of senescent cytokines between others.

Figure 3

One of the consequences of the aging process is the diminution of autophagic capacity. Consequently, this diminution predisposes the individual to accumulation of cellular damage and senescence activation. In the immune system, this process is called immunosenescence and is accompanied by chronic inflammation. Several pathogens that induce chronic infections are able to activate or accelerate the immunosenescence process and in this way, their elimination by the host tends to be less effective.