Early detection of accelerated aging and cellular decline (AACD): A consensus statement

The cellular hallmarks of accelerated aging and their clinical expression may be grouped using the terms 'accelerated aging and cellular decline' (AACD) and/or 'age-associated cellular decline'. This construct is designed to capture the biological background predisposing the development of age-related conditions. By classifying risk factors, early indicators, and clinical differentiators of AACD through expert consensus, this study aimed to identify the signs, symptoms, and markers indicative of AACD. In doing so, this work paves the way for future implementation of the AACD concept in the clinical and research settings. An interdisciplinary panel of experts with clinical and research expertise was selected to participate in a virtual workshop to discuss AACD. A modified nominal group technique was used to establish consensus among the group. An extended group of international experts critically reviewed an early draft of the manuscript, and their feedback was then incorporated into the model. Experts identified 13 factors predisposing to or clinically manifesting AACD. Among these, chronic diseases, obesity, and unfavorable genetic background were considered as the most important. There was a consensus that a gradual and nonspecific development often characterizes AACD, making its clinical detection potentially challenging. In addition, signs and symptoms might have multifactorial causes and overlapping origins, such as genetic and epigenetic predispositions. As a result, an initial checklist was outlined, listing clinical factors of special relevance (e.g., fatigue, low quality of sleep, and low mood) to represent early manifestations of the organism's exhaustion, which are also frequently neglected in the clinical setting. Differentiating AACD from other conditions is essential. The use of a combination of biomarkers was proposed as a viable method in a two-step process of differentiation: 1) identification of early AACD clinical indicators, followed by 2) symptom and biomarker confirmation with a focus on system domains (to be potentially targeted by future specific interventions). Although the AACD construct is not yet ready for routine use in clinical practice, its operationalization may support the early identification of age-related conditions (when this might still be amenable to reversion) and also encourage preventative interventions. Further investigation is needed to establish specific biomarkers that confirm independent risk factors for AACD and provide a more definitive structure to the concept of AACD (and age-associated cellular decline).