Animal Models of Aging Research: Implications for Human Aging and Age-Related Diseases

Abstract

Aging is characterized by an increasing morbidity and functional decline that eventually results in the death of an organism. Aging is the largest risk factor for numerous human diseases, and understanding the aging process may thereby facilitate the development of new treatments for age-associated diseases. The use of humans in aging research is complicated by many factors, including ethical issues; environmental and social factors; and perhaps most importantly, their long natural life span. Although cellular models of human disease provide valuable mechanistic information, they are limited in that they may not replicate the in vivo biology. Almost all organisms age, and thus animal models can be useful for studying aging. Herein, we review some of the major models currently used in aging research and discuss their benefits and pitfalls, including interventions known to extend life span and health span. Finally, we conclude by discussing the future of animal models in aging research.

Effects of aging on liver microcirculatory function and sinusoidal phenotype

“…Therefore, it is critical to understand the molecular basis of aging and to identify possible approaches for therapeutic intervention in case major abnormalities are detected (Longo et al, 2015; Mitchell, Morten, Longo, & Cabo, 2015). Although previous studies described the impact of aging on the vasculature of different territories, in the specific field of Hepatology, very little is known about the liver microcirculatory function and the molecular status of hepatic sinusoidal cells in aging (Le Couteur & McLean, 1998; Le Couteur et al, 2001).…”

Animal models of frailty: current applications in clinical research

“…Animal models of aging have been used for decades to investigate both the underlying mechanisms of aging and interventions to increase lifespan and healthspan 21. The relatively short lifespans, reduced genetic diversity, control of environmental factors, and the ability to test a variety of outcomes including stress responses, metabolic outcomes, behavioral and functional assessments, and serum, urine, and tissue analysis make animal models invaluable tools in the study of aging 21.…”

“…The relatively short lifespans, reduced genetic diversity, control of environmental factors, and the ability to test a variety of outcomes including stress responses, metabolic outcomes, behavioral and functional assessments, and serum, urine, and tissue analysis make animal models invaluable tools in the study of aging 21. There has been a recent focus on developing animal models of frailty22 to explore mechanisms, interventions, and outcomes associated with frailty.…”

“…It has not yet been investigated, but it is possible that transgenic mouse models of premature aging such as the Werner syndrome mice or the Hutchinson–Gilford mice21 could also be used to investigate frailty. Biological changes such as inflammation and sarcopenia, as well as the mouse frailty phenotype and the mouse clinical FI could be easily assessed in premature aging models resulting in faster and cheaper studies than those that use naturally aging mice.…”

“…C57BL/6 mice are the classical inbred mouse strain commonly used for aging research due to the wealth of phenotypic and genotypic information available 21. They are also a popular model because they develop similar age-related changes as are seen in humans including reduced activity and vascular, bone, and inflammation changes 53–56.…”