Brain aging: A critical reappraisal

Abstract

Despite remarkable scientific advancements in recent years, much about the human brain still remains a mystery, particularly in the context of brain aging and associated disorders. Understanding of the factors that influence brain integrity late in life will help to maintain healthy brain functions. This is indeed a difficult task because in several cases, normal brain aging switches to pathological aging associated with drastic deterioration in cognitive abilities, motor skills and mood resulting in neurological diseases, ranging from late onset neurodegenerative diseases such as Alzheimer’s and Parkinson’s to early onset neuropsychiatric disorders such as schizophrenia and bipolar disorder. Brain aging is accompanied by several anatomical, cellular and molecular alterations including reduction in brain volume, protein turnover, increase in protein aggregation, impairment in neural plasticity, perturbed calcium homeostasis, neuronal survival and neuroinflammation, eventually affecting brain functions with increased incidence of neurological disorders. Factors like stress, depression, hypertension as well as obesity accelerate the aging of brain contributing to neurodegeneration and associated cognitive deficits. During the past decades, technical advances including microarray, neuroimaging and behavioral paradigms have helped to get a holistic picture of age-associated alterations in the brain. Here we review the current understanding of age-related structural and functional changes in the brain and how these changes might contribute to vulnerability for developing age-related neurological diseases and designing potential therapeutic avenues. Taken together, the findings suggest that adoption of certain neuroprotective strategies like dietary restriction, antioxidant supplementation, low alcohol intake, less exposure to stressors, environmental enrichment and lifestyle modulations involving exercise and intellectual brain training programs can be beneficial to delay the loss of brain integrity during aging.