The Aging Human Liver: The Weal and Woe of Evolutionary Legacy

Abstract

Aging is characterized by the progressive decline of biological integrity and its compensatory mechanisms as well as immunological dysregulation. This goes along with an increasing risk of frailty and disease. Against this background, we here specifically focus on the aging of the human liver. For the first time, we shed light on the intertwining evolutionary underpinnings of the liver’s declining regenerative capacity, the phenomenon of inflammaging, and the biotransformation capacity in the process of aging. In addition, we discuss how aging influences the risk for developing nonalcoholic fatty liver disease, hepatocellular carcinoma, and/or autoimmune hepatitis, and we describe chronic diseases as accelerators of biological aging.

SAMM50-rs2073082, -rs738491 and -rs3761472 Interactions Enhancement of Susceptibility to Non-Alcoholic Fatty Liver Disease

“…Aging, a major risk factor for increased susceptibility to certain diseases, is characterized by a gradual physiological process that affects all systems of the body, including cells, tissues and organs, which ultimately leads to impaired biological function of the organism [ 33 ]. Various endogenous and exogenous factors, such as genetic makeup or dietary habits, also have a significant impact on individualized aging [ 34 ]. It has been reported that aging, particularly hepatic age, can promote the development of steatosis, non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma by reducing the regenerative capacity, biotransformation and increasing inflammation of the liver [ 34 ].…”

“…Various endogenous and exogenous factors, such as genetic makeup or dietary habits, also have a significant impact on individualized aging [ 34 ]. It has been reported that aging, particularly hepatic age, can promote the development of steatosis, non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma by reducing the regenerative capacity, biotransformation and increasing inflammation of the liver [ 34 ]. In a territory-wide retrospective cohort study, Zhang et al [ 35 ] found that most patients with NAFLD and T2DM developed liver-related events or cirrhosis after age 50, suggesting that aging is an independent and strong predictor of NAFLD.…”

Liver Diseases: Science, Fiction and the Foreseeable Future

“…Finally, one might arguably include Nancy Leslie Rutherford Bucher (1913Bucher ( -2017 as another founding mother in this illustrious circle [11]. In 1964, she was the first to show that the most striking effect of aging on the liver is the decline of the organ's remarkable capacity to 'regenerate' (a process correctly termed 'compensatory hyperplasia') in the event of tissue loss [12].…”

“…In 1964, she was the first to show that the most striking effect of aging on the liver is the decline of the organ's remarkable capacity to 'regenerate' (a process correctly termed 'compensatory hyperplasia') in the event of tissue loss [12]. Not only epistemologically, but also in terms of practical medical relevance, this decline must be viewed against an evolutionary background spanning eons that helps to explain aging-related hepatic and systemic pathological effects, which may lead to novel options for their antagonization [11,13].…”

“…Therefore, as the body of knowledge about the liver and aging, as well as the available methodologies, have increased considerably in recent decades, they can-and definitely should-now be applied rigorously to minimize the negative health effects and their social and economic implications. This includes all hepatic aspects of aging covering genomics and epigenomics [48], age-related changes of the hepatic transcriptome [51], dietary habits in conjunction with medically based guidelines for the food industry vis-àvis the continuous increase in metabolic disorders [52], and, last but not least, important evolutionary underpinnings of hepatic biology that go along with an increased likelihood for developing certain chronic diseases, while chronic diseases in turn accelerate biological aging [11]. We therefore have an impressive "toolbox" at our disposal.…”