A Review of Some of What is Known of Aging in Liver Tissue

Autophagy is the name given to a collection of cellular housekeeping processes that recycle damaged and otherwise unwanted proteins and structures in the cell. Increased autophagy is a common feature of interventions that alter metabolism and slow aging in short-lived species. This is well studied in the context of calorie restriction, and is likely an important mechanism in mTOR inhibition, such as via rapamycin. Still, the only really impressive results produced via upregulation of autophagy to date are in the liver, starting with the use of LAMP2A as a target to improve operation of the lyosomal portion of autophagy in aged animals. In that context, it is interesting to take a look at what is known of aging at the detail level in liver tissue.

During aging, the liver undergoes a series of degenerative changes. Briefly, it presents a progressive decrease in functional liver mass, thus reducing its functional reserve, making it more difficult to maintain homeostasis and vulnerable to external stress or damage. Till now, the mechanisms underlying liver aging still remain unclear. As we known, the main causes of aging are DNA damage, telomere shortening, epigenetic alterations, and impairment of proteostasis.

The aged liver is usually accompanied with failure of regeneration, metabolic dysfunction, redox imbalance, and development of chronic or malignant liver diseases. The impairment of regenerative capacity in the aged liver is affected by both intracellular factors and extracellular factors. Intriguingly, we may be able to recover their regenerative capacity via changing a microenvironment for the senescent hepatocytes. The aging-related alterations in the liver form a unique microenvironment and affect a series of physiological processes. Moreover, this unique microenvironment may function as a vital role that causes the liver to become susceptible to chronic diseases or tumors. For instance, it affects the fate of hepatocytes and promotes neoplastic development. Moreover, hepatocytes in this microenvironment are more susceptible to ischemia/reperfusion (I/R) injury.

Of particular interest is the way to effectively eliminate the effects of aging and reverse the unique aging microenvironment in the aged liver. Modulation of autophagy could function as an effective strategy for reversing aging in the liver. Autophagy mainly functions as a cytoprotective role in liver diseases. Modulation of autophagy could markedly alleviate aging-related liver injury, promote liver regeneration, block I/R induced injury, and reverse the aging microenvironment in the aged liver.

Link: https://doi.org/10.3389/fmed.2022.842024

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