Reappraisal of the Concept of Accelerated Aging in Neurodegeneration and Beyond

Background: Genetic and epigenetic changes, oxidative stress and inflammation influence the rate of aging, which diseases, lifestyle and environmental factors can further accelerate. In accelerated aging (AA), the biological age exceeds the chronological age. Objective: The objective of this study is to reappraise the AA concept critically, considering its weaknesses and limitations. Methods: We reviewed more than 300 recent articles dealing with the physiology of brain aging and neurodegeneration pathophysiology. Results: (1) Application of the AA concept to individual organs outside the brain is challenging as organs of different systems age at different rates. (2) There is a need to consider the deceleration of aging due to the potential use of the individual structure–functional reserves. The latter can be restored by pharmacological and/or cognitive therapy, environment, etc. (3) The AA concept lacks both standardised terminology and methodology. (4) Changes in specific molecular biomarkers (MBM) reflect aging-related processes; however, numerous MBM candidates should be validated to consolidate the AA theory. (5) The exact nature of many potential causal factors, biological outcomes and interactions between the former and the latter remain largely unclear. Conclusions: Although AA is commonly recognised as a perspective theory, it still suffers from a number of gaps and limitations that assume the necessity for an updated AA concept.