Models for preclinical studies in aging-related disorders: One is not for all.

Transl Med UniSa. 2016 Jan 31;13:4-12. eCollection 2015.

Santulli G¹, Borras C², Bousquet J³, Calzà L⁴, Cano A⁵, Illario M⁶, Franceschi C⁷, Liotta G⁸, Maggio M⁹, Molloy WD¹⁰, Montuori N⁶, O'Caoimh R¹¹, Orfila F¹², Rauter AP¹³, Santoro A¹⁴, Iaccarino G¹⁵.

Author information

• ¹Department of Physiology and Cellular Biophysics, Columbia University Medical Center; College of Physicians & Surgeons, New York, USA;
• ²Department of Physiology, University of Valencia /INCLIVA, Valencia, Spain;
• ³MACVIA-LR, European Innovation Partnership on Active and Healthy Ageing Reference Site, University Hospital of Montpellier, France;; INSERM, VIMA : Ageing and chronic diseases. Epidemiological and public health approaches, Paris, France; Université Versailles St-Quentin-en-Yvelines, France;
• ⁴Health Sciences and Technologies - Interdepartmental Center for Industrial Research (HST-ICIR) University of Bologna;
• ⁵Department of Pediatrics, Obstetrics and Gynecology, University of Valencia/INCLIVA, Valencia, Spain;
• ⁶Department of Translational Medical Sciences, Federico II University, and R&D Unit, Federico II University Hospital;
• ⁷IRCCS Institute of Neurological Sciences, Bologna;; National Research Council of Italy, CNR, Institute for Organic Synthesis and Photoreactivity (ISOF) and Institute of Molecular Genetics, Bologna, Italy;; Dept. of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy;
• ⁸Department of Biomedicine and Prevention "Tor Vergata" University of Rome, Italy;
• ⁹Department of Clinical and Experimental Medicine, University of Parma; University Hospital of Parma.
• ¹⁰Centre for Gerontology and Rehabilitation, University College Cork, Ireland;
• ¹¹Centre for Gerontology and Rehabilitation, University College Cork, Ireland;; Health Research Board, Clinical Research Facility Galway, National University of Ireland, Galway, Ireland;
• ¹²Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Barcelona, Spain;
• ¹³Departamento de Quimica e Bioquímica, Universidade de Lisboa, Portugal;
• ¹⁴Dept. of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy;
• ¹⁵Department of Medicine and Surgery, University of Salerno, Italy.

Abstract

Preclinical studies are essentially based on animal models of a particular disease. The primary purpose of preclinical efficacy studies is to support generalization of treatment-effect relationships to human subjects. Researchers aim to demonstrate a causal relationship between an investigational agent and a disease-related phenotype in such models. Numerous factors can muddle reliable inferences about such cause-effect relationships, including biased outcome assessment due to experimenter expectations. For instance, responses in a particular inbred mouse might be specific to the strain, limiting generalizability. Selecting well-justified and widely acknowledged model systems represents the best start in designing preclinical studies, especially to overcome any potential bias related to the model itself. This is particularly true in the research that focuses on aging, which carries unique challenges, mainly attributable to the fact that our already long lifespan makes designing experiments that use people as subjects extremely difficult and largely impractical.

KEYWORDS:

aging; animal models; cardiovascular medicine; frailty; multimorbidity; preclinical studies; rodents; swine