View source for Brain Aging

The brain is remarkably sensitive to the effects of aging, displaying as changes in structure and cognitive capacity, as well as increased risk for developing certain neurological disorders.{{pmid|23333262}}{{pmid|28159687}} Brain health refers to the maintenance of brain functions in several aspects:

# '''Cognitive health''': the ability to adequately think, learn, and remember;
# '''Motor function:''' the ability to control movements and balance;
# '''Emotional health''': the ability to interpret and respond to emotions;
# '''Tactile function''': the ability to feel and respond to sensations of touch, including pressure, pain, and temperature.<ref>Cognitive Health and Older Adults. https://www.nia.nih.gov/health/cognitive-health-and-older-adults (accessed Apr 26, 2023).</ref>

At the molecular level, brain aging, similarly to all other organ systems, is characterized by changes in gene expression, epigenetic modifications, and alterations in protein synthesis and turnover. It is also associated with the accumulation of toxic protein aggregates, such as β-amyloid and tau, which can disrupt neuronal function and contribute to the development of neurodegenerative diseases.{{pmid|34118939}}{{pmid|34485280}} At the cellular level, brain aging is characterized by the accumulation of cell damage, including oxidative stress, DNA damage, and protein misfolding. This damage can lead to the dysfunction and death of brain cells, including neurons and glia. Studies have shown that dendritic arbors and spines decrease in size and/or number in cortex as a result of aging.{{pmid|12902394}}{{pmid|23069756}} Aging also sets off a decline in the regenerative capacity of brain cells, such as decreased neurogenesis and oligodendrogenesis.{{pmid|33732142}}{{pmid|25205996}}

At the system level, brain aging includes changes in brain connectivity and function such as alterations in neural activity, neurotransmitter function, and white matter integrity. Aging is associated with a decline in the function of essential neurotransmitter systems such as dopamine and acetylcholine, which can lead to cognitive impairment. Brain aging is associated also with changes in brain structure, such as the loss of gray matter volume and changes in white matter microstructure.{{pmid|29874566}}{{pmid|16461469}}−{{pmid|12548289}} At the organismal level, brain aging is associated with declines in cognitive function, sensory function, and motor function. Age-related changes in the cardiovascular system, immune system, and endocrine system can also impact brain function and contribute to age-related neurodegenerative diseases.{{pmid|34485280}}{{pmid|34600936}}

Hallmarks of aging, including mitophagy, cellular senescence, genomic instability, and protein aggregation, have been related to the age-associated neurodegenerative and cerebrovascular disorders.{{pmid|31501588}} Furthermore, the most frequent neurodegenerative diseases share the common attribute of protein aggregation. The aggregation of senile plaques containing amyloid-β peptide and the formation of intraneuronal tau containing neurofibrillary tangles in Alzheimer’s disease and the accumulation of misfolded α-synuclein in Parkinson’s disease are major pathogenic aspects of these diseases.{{pmid|26209472}} Protein aggregation is also a feature of amyotrophic lateral sclerosis and frontotemporal lobar dementia.{{pmid|27540165}}

Brain tissues comprise primarily postmitotic cells, including neurons and oligodendrocytes, which are sensitive to age-related alterations such as DNA damage or methylation. Indeed, Parkinson’s disease patients have been reported to consistently exhibit DNA methylation patterns associated with advanced aging.{{pmid|26655927}} Advanced aging has been also related to enhanced mitochondrial dysfunction and damage, thus promoting neurodegeneration via the production of ROS and the advancing neuroinflammation.{{pmid|34485280}}

In addition to the most common age-associated neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases and stroke, others included are age-related macular degeneration associated with blurred or distorted vision; multiple sclerosis associated with myelin damage, which disturbs the information flow within brain, and between brain and body; amyotrophic lateral sclerosis (Lou Gehrig’s disease) affecting motor neurons thus causing loss of muscle control; Huntington’s disease associated with involuntary movements, difficulty with coordination, and changes in mood and behavior; and various kinds of dementias including Lewy bodies dementia characterized by the presence of abnormal protein deposits in the brain, which causes changes in attention and alertness, visual hallucinations, and movement disorders, and vascular dementia associated with damage to the blood vessels that supply blood to the brain, which causes memory loss, difficulty with decision-making, and changes in mood and behavior.{{pmid|34485280}}{{pmid|16461469}}{{pmid|15190177}}<ref>Neurological Disorders - a Common Problem of Aging. https://reliantmedicalgroup.org/blog/2014/08/05/neurological-disorders-common-problem-aging/ (accessed Apr 26, 2023).</ref>

There is a steady, nearly exponential growth of the number of journal publications related to brain aging in the CAS Content Collection over time, remarkably intense in the last two years (FigureFigure77), a sign of the enhanced scientific interest in this area. At the same time, patenting activity is low, probably awaiting the knowledge accumulation reaching a critical level.