LAUSR

Both “aging” and the “brain” are vast topics that certainly merit study each in their own right, but when placed together, one seems hard put to know where to start. For many years, it has been fashionable to pose questions to trainees and colleagues such as “Why do we age?” as if a question so simple could easily yield profound insights. One’s first temptation is to conclude that time passes and therefore things get older. However, this ignores the fact that aging is a process that appears to result from the confluence of genetic and environmental factors. Indeed, one definition of aging is that of a coordinated response to a changing environment, both internal and external, that culminates in magnitude as we approach the end of the life span. In that many age-associated changes in our bodies are associated with increased susceptibility to injury and disease, there is merit in exploring how to mitigate the effects of aging in order to lead healthier, happier, and longer lives. As with the general phenomenon of aging, the brain is equally inscrutable in revealing its secrets and properties. Whether the human brain is the most complex “thing” is debatable, but nobody seems to doubt that the process of the brain understanding itself is truly remarkable, almost science fiction in its improbability, yet real and palpable with regular advances improving the human condition. Given the rapidly accelerating aging of populations throughout the world—in the USA, Europe, Japan, and China—the ability to intervene in meaningful ways across our advancing years has become a top scientific and medical priority. In this special issue of Neurotherapeutics, a wide range of articles bring the reader into the latest developments in the field of healthy brain aging. The challenge in the field is to create a coherent narrative of what appear to be isolated strands, and combine multiple physiologic changes associated with myriad disease states into efficient and doable therapeutics over wide populations. Several papers in this issue approach these weighty issues from a wide-ranging perspective, while others explore a single system or therapeutic modality in greater detail. To begin, Lupo et al. [1] reviewmolecular signatures of the aging brain. This approach of utilizing basic science as a platform to devise interventions is still in its early stages of application to the aging brain. Which of the many -omics approaches will ultimately lead to specific interventions to improve brain health remains unsettled, but cooperative science across large groups of investigators is accelerating the discovery of knowledge and guiding future interventions. The breadth of any individual approach will need to be considered, since multiple feedback loops and buffering of genomic, proteomic, and metabolomic systems underscore the significant challenge in finding a “magic bullet” within the tangles of these systems. Next, Bah et al. [2] review sleep as a therapeutic target for healthy brain aging. Maintaining proper sleep is a major clinical challenge in neurodegenerative diseases of aging that are characterized by prominent sleep disturbances, such as Parkinson’s disease (PD), Dementia with Lewy bodies, variants of prion disorders, and Alzheimer’s disease (AD). Further, sleep deprivation is endemic in our society, and in some demanding professions, the extent of sleep deprivation endured by individuals striving for productivity in their field is paradoxically worn as a badge of honor. The long-term negative health effects of chronic sleep deprivation and disturbance are profound, and this remains an active area of research. For * Alan J. Lerner [email protected]