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

Dedication

This contribution is dedicated to the memory of the one who started it all: Nancy Leslie Rutherford Bucher, M.D. (1913 – 2017)

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.

Zusammenfassung

Altern ist gekennzeichnet durch die progrediente Abnahme der biologischen Integrität und ihrer kompensatorischen Mechanismen sowie immunologische Dysregulation. Dies geht mit einem zunehmenden Risiko für Gebrechlichkeit und Krankheit einher. Vor diesem Hintergrund fokussieren wir auf die Alterung der menschlichen Leber. Dabei beleuchten wir erstmals die ineinandergreifenden evolutiven Fundamente der abnehmenden Leberregenerationsfähigkeit, des Inflammaging-Phänomens und der Biotransformationskapazität im Alterungsprozess. Zudem diskutieren wir den Einfluss des Alterns auf das Risko, eine nichtalkoholische Fettlebererkrankung, ein Hepatozelluläres Karzinom und/oder eine Autoimmunhepatitis zu entwickeln, und wir beschreiben chronische Erkrankungen als Beschleuniger des biologischen Alterns.

Schlüsselwörter

Leberregeneration - Inflammaging - Biotransformation - nicht-alkoholische Fettlebererkrankung - Hepatozelluläres Karzinom - Horvath clock

Keywords

liver regeneration - inflammaging - biotransformation - nonalcoholic fatty liver disease - hepatocellular carcinoma - Horvath clock

Publication History

Received: 26 September 2022

Accepted after revision: 04 December 2022

Article published online:
09 January 2023

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