Open AccessPathways to Brain Aging and Their Modifiers: Free-Radical-Induced Energetic and Neural Decline in Senescence (FRIENDS) Model - A Mini-Review
Author(s) -
Naftali Raz,
Ana M. Daugherty
Publication year - 2017
Publication title -
gerontology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.397
H-Index - 94
eISSN - 1423-0003
pISSN - 0304-324X
DOI - 10.1159/000479508
Subject(s) - neuroscience , senescence , aging brain , brain aging , context (archaeology) , brain structure and function , cognition , psychology , neuroanatomy , neuroimaging , cognitive decline , white matter , human brain , dementia , extant taxon , biology , evolutionary biology , medicine , magnetic resonance imaging , pathology , paleontology , disease , radiology , microbiology and biotechnology
In this mini-review, we survey the extant literature on brain aging, with the emphasis on longitudinal studies of neuroanatomy, including regional brain volumes and white matter microstructure. We assess the impact of vascular, metabolic, and inflammatory risk factors on the trajectories of change in regional brain volumes and white matter properties, as well as the relationships between neuroanatomical and physiological changes and their influence on cognitive performance. We examine these findings in the context of current biological theories of aging and propose the means of integrating noninvasive measures - spectroscopic indices of brain energy metabolism and regional iron deposits - as valuable proxies for elucidating the basic neurobiology of human brain aging. In a brief summary of the recent findings pertaining to age-related changes in the brain structure and their impact on cognition, we discuss the role of vascular, metabolic, and inflammatory risk factors in shaping the trajectories of change. Drawing on the extant biological theories of aging and mindful of the brain's role as a disproportionately voracious energy consumer in mammals, we emphasize the importance of the fundamental bioenergetic mechanisms as drivers of age-related changes in brain structure and function. We sketch out a model that builds on the conceptualization of aging as an expression of cumulative cellular damage inflicted by reactive oxygen species and ensuing declines in energy metabolism. We outline the ways and means of adapting this model, Free-Radical-Induced Energetic and Neural Decline in Senescence (FRIENDS), to human aging and testing it within the constraints of noninvasive neuroimaging.