The causes of aging remain unknown, but they are probably intimately linked to a multifactorial process that affects cell networks to varying degrees. Although a growing number of aging and Alzheimer’s disease (AD) animal models are available, a more comprehensive and physiological mouse model is required. In this context, the senescence-accelerated mouse prone 8 (SAMP8) has a number of advantages, since its rapid physiological senescence means that it has about half the normal lifespan of a rodent. In addition, according to data gathered over the last five years, some of its behavioral traits and histopathology resemble AD human dementia. SAMP8 has remarkable pathological similarities to AD and may prove to be an excellent model for acquiring more in-depth knowledge of the age-related neurodegenerative processes behind brain senescence and AD in particular. We review these facts and particularly the data on parameters related to neurodegeneration. SAMP8 also shows signs of aging in the immune, vascular, and metabolic systems, among others. 1. Introduction to the Model: The Origin of Senescence-Accelerated Mouse Strains The free radical and mitochondrial theories of aging seem to be the two most prominent theories that have survived the test of time [1, 2]. These theories claim that oxidative stress within mitochondria can lead to a vicious cycle in which damaged mitochondria produce increased amounts of reactive oxygen species, leading in turn to frailty and progressive disability. If aging-associated processes result from oxidative stress, then some of the most prevalent neurodegenerative diseases associated mainly with the deleterious effects of time on cellular mechanisms can also be linked to an imbalance in the homeostatic mechanism controlling oxidative processes in the whole organism and particularly in brain [3]. The main neurodegenerative diseases are Alzheimer’s (AD), Parkinson’s, Huntington’s, or amyotrophic lateral sclerosis [4, 5]. Of these, AD is the most prevalent. Many problems have had to be overcome in the last two decades of research on aging and associated neurodegenerative diseases. These include a lack of diagnostic markers or detection as well as difficulties in discovering the main molecular and cellular pathways and the causes of the deleterious effects of senescence. In basic research, the main stumbling block has clearly been the lack of an in vivo model that naturally assimilates what happens in humans. Aging models are slow or include rare and specific mutations, such as mutated Klotho protein [6]. In the case of AD, the
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