a1 Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, NC, USA
a2 Program in Neuroscience, Wake Forest University School of Medicine, Winston-Salem, NC, USA
a3 J. Paul Sticht Center on Aging, Wake Forest University School of Medicine, Winston-Salem, NC, USA
The last three decades produced a striking increase in investigations of the neurobiological basis of brain aging and aging-related changes in neural and cognitive function. Experimental and clinical studies of aging have become more valuable as the population, at least in industrialized countries, has become ‘greyer’. The increase in adult life expectancy that occurred in the twentieth century produced the motivation and necessity to invest resources in increasing ‘health span’ as well as lifespan, in order to maximize quality of life and minimize the financial and social burdens associated with disability in the later years of life. Specific interest in the aging nervous system is driven by recognition that increased longevity has little appeal for most people unless it is accompanied by maintenance of cognitive abilities. Indeed, surveys of older individuals routinely show that loss of mental capacity is among their greatest fear. In recent years, neuroscientists and gerontologists, with a variety of training and experimental approaches, have applied increasingly powerful quantitative methods to investigate why neural function declines with age. New animal model systems have been developed and old ones have become better characterized and standardized. The necessary and important descriptive studies that dominated the field in earlier years are increasingly supplemented by more hypothesis-driven research, resulting in sophisticated investigations and models of the mechanisms of brain aging. This review provides a selective overview of recent and current research on brain aging. The focus throughout will be on normal brain aging and the moderate cognitive changes that often accompany it, not on aging-related neurodegenerative diseases that result in dementia. To provide a context for studies of neurobiological changes in the aging brain, a brief overview of the types of cognitive changes that are commonly seen in aging humans is first provided. The remainder of the review focuses on animal studies that are progressively overcoming the unique challenges of aging research to reveal the neurobiological mechanisms of aging-related cognitive dysfunction, and suggest new targets for therapies to prevent or ameliorate cognitive decline.
c1 Address for correspondence: DR Riddle, Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1010, USA.