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[[File:Brain 090407.jpg|right|frameless]]
[[File:Brain 090407.jpg|right|frameless]]
'''Brain aging''' is a process of transformation of the brain in older age in humans, including changes all individuals experience and those of illness (including unrecognised illness).
== Overview ==
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:
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:


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# '''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>
# '''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 Alterations|epigenetic modifications]], and [[Loss of Proteostasis|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 Disorders|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}}
== Molecular and Cellular Changes ==
At the molecular level, brain aging, similarly to all other organ systems, is characterized by changes in gene expression, [[Epigenetic Alterations|epigenetic modifications]], and [[Loss of Proteostasis|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 Disorders|neurodegenerative diseases]].{{pmid|34118939}}{{pmid|34485280}} At the cellular level, brain aging is characterized by the accumulation of cell damage, including [[Oxidative Stress|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 Disorders|neurodegenerative diseases]].{{pmid|34485280}}{{pmid|34600936}}
== System and Organismal Level Changes ==
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|37024597}}{{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 Disorders|neurodegenerative diseases]].{{pmid|34485280}}{{pmid|34600936}}


== Hallmarks of Aging and Neurodegenerative Disorders ==
[[Hallmarks of Aging|Hallmarks of aging]], including mitophagy, [[Cellular Senescence|cellular senescence]], [[Genomic Instability|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}}
[[Hallmarks of Aging|Hallmarks of aging]], including mitophagy, [[Cellular Senescence|cellular senescence]], [[Genomic Instability|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}}


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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>
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 (Figure​Figure77), 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.
== Brain Size ==
[[File:Brain weight age.gif|thumb|Average brain weight for males and females over lifespan. From the study ''Changes in brain weights during the span of human life.''|360x360px]]A human baby's brain at birth averages 369&nbsp;cm<sup>3 </sup>and increases, during the first year of life, to about 961&nbsp;cm<sup>3</sup>, after which the growth rate declines. Brain volume peaks at the teenage years,{{pmid|10491603}} and after the age of 40 it begins declining at 5% per decade, speeding up around 70.{{pmid|16461469}} Average adult male brain weight is {{convert|1345|g}}, while an adult female has an average brain weight of {{convert|1222|g}}.<ref>{{Cite book|url = https://books.google.com/books?id=u1bwQj7qdsYC|title = Reader in Gender archaeology|access-date = 2014-09-21|publisher = Routlegde|author1=Kelley Hays |author2=David S. |isbn = 9780415173605|year = 1998}}</ref> (This does not take into account neuron density nor brain-to-body mass ratio; men on average also have larger bodies than women.)


== Brain Size ==
Total cerebral and gray matter volumes peak during the ages from 10–20 years (earlier in girls than boys), whereas white matter and ventricular volumes increase. There is a general pattern in neural development of childhood peaks followed by adolescent declines (e.g. synaptic pruning). Consistent with adult findings, average cerebral volume is approximately 10% larger in boys than girls. However, such differences should not be interpreted as imparting any sort of functional advantage or disadvantage; gross structural measures may not reflect functionally relevant factors such as neuronal connectivity and receptor density, and of note is the high variability of brain size even in narrowly defined groups, for example children at the same age may have as much as a 50% differences in total brain volume.{{pmid|18346658}}
[[File:Brain weight age.gif|thumb|Average brain weight for males and females over lifespan. From the study ''Changes in brain weights during the span of human life.''|360x360px]]A human baby's brain at birth averages 369&nbsp;cm<sup>3 </sup>and increases, during the first year of life, to about 961&nbsp;cm<sup>3</sup>, after which the growth rate declines. Brain volume peaks at the teenage years,<ref>{{cite journal |last1=Giedd |first1=Jay N. |last2=Blumenthal |first2=Jonathan |last3=Jeffries |first3=Neal O. |last4=Castellanos |first4=F. X. |last5=Liu |first5=Hong |last6=Zijdenbos |first6=Alex |last7=Paus |first7=Tomáš |last8=Evans |first8=Alan C. |last9=Rapoport |first9=Judith L. |title=Brain development during childhood and adolescence: a longitudinal MRI study |journal=Nature Neuroscience |date=October 1999 |volume=2 |issue=10 |pages=861–863 |doi=10.1038/13158 |pmid=10491603 |s2cid=204989935 }}</ref> and after the age of 40 it begins declining at 5% per decade, speeding up around 70.<ref>{{Cite journal|title=Ageing and the brain|journal=Postgraduate Medical Journal|url=http://ncbi.nlm/|last=Peters|first=R.|pmc=2596698|pmid=16461469|doi=10.1136/pgmj.2005.036665|volume=82|issue=964|year=2006|pages=84–8|access-date=2019-09-12|archive-date=2013-07-15|archive-url=https://web.archive.org/web/20130715163844/http://www.ncbi.nlm/|url-status=dead}}</ref> Average adult male brain weight is {{convert|1345|g}}, while an adult female has an average brain weight of {{convert|1222|g}}.<ref>{{Cite book|url = https://books.google.com/books?id=u1bwQj7qdsYC|title = Reader in Gender archaeology|access-date = 2014-09-21|publisher = Routlegde|author1=Kelley Hays |author2=David S. |isbn = 9780415173605|year = 1998}}</ref> (This does not take into account [[List of animals by number of neurons|neuron density]] nor [[brain-to-body mass ratio]]; men on average also have larger bodies than women.) Males have been found to have on average greater cerebral, cerebellar and cerebral cortical lobar volumes, except possibly left parietal.<ref name="Ross2006">{{cite journal |last1=Carne |first1=Ross P. |last2=Vogrin |first2=Simon |last3=Litewka |first3=Lucas |last4=Cook |first4=Mark J. |title=Cerebral cortex: An MRI-based study of volume and variance with age and sex |journal=Journal of Clinical Neuroscience |date=January 2006 |volume=13 |issue=1 |pages=60–72 |doi=10.1016/j.jocn.2005.02.013 |pmid=16410199 |s2cid=20486422 }}</ref> The gender differences in size vary by more specific brain regions. Studies have tended to indicate that men have a relatively larger [[amygdala]] and [[hypothalamus]], while women have a relatively larger [[caudate nucleus|caudate]] and [[Hippocampus|hippocampi]]. When covaried for [[cranial capacity|intracranial volume]], height, and weight, Kelly (2007) indicates women have a higher percentage of [[gray matter]], whereas men have a higher percentage of [[white matter]] and [[cerebrospinal fluid]]. There is high variability between individuals in these studies, however.<ref name="Kelly2007" />


However, Yaki (2011) found no [[statistically significant]] gender differences in the gray matter ratio for most ages (grouped by decade), except in the 3rd and 6th decades of life in the sample of 758 women and 702 men aged 20–69.<ref name="taki2011">{{Cite journal | last1 = Taki | first1 = Y. | last2 = Thyreau | first2 = B. | last3 = Kinomura | first3 = S. | last4 = Sato | first4 = K. | last5 = Goto | first5 = R. | last6 = Kawashima | first6 = R. | last7 = Fukuda | first7 = H. | editor1-last = He | editor1-first = Yong | title = Correlations among Brain Gray Matter Volumes, Age, Gender, and Hemisphere in Healthy Individuals | doi = 10.1371/journal.pone.0022734 | journal = PLOS ONE | volume = 6 | issue = 7 | pages = e22734 | year = 2011 | pmid = 21818377| pmc =3144937 | bibcode = 2011PLoSO...622734T | doi-access = free }}</ref> The average male in their third decade (ages 20–29) had a significantly higher gray matter ratio than the average female of the same age group. In contrast, among subjects in their sixth decade, the average woman had a significantly larger gray matter ratio, though no meaningful difference was found among those in their 7th decade of life.
Significant dynamic changes in brain structure take place through adulthood and aging, with substantial variation between individuals. In later decades, men show greater volume loss in whole brain volume and in the frontal lobes, and temporal lobes, whereas in women there is increased volume loss in the hippocampi and parietal lobes.{{pmid|17544382}} Men show a steeper decline in global gray matter volume, although in both sexes it varies by region with some areas exhibiting little or no age effect. Overall white matter volume does not appear to decline with age, although there is variation between brain regions.{{pmid|11525331}}


Total cerebral and gray matter volumes peak during the ages from 10–20 years (earlier in girls than boys), whereas white matter and ventricular volumes increase. There is a general pattern in neural development of childhood peaks followed by adolescent declines (e.g. [[synaptic pruning]]). Consistent with adult findings, average cerebral volume is approximately 10% larger in boys than girls. However, such differences should not be interpreted as imparting any sort of functional advantage or disadvantage; gross structural measures may not reflect functionally relevant factors such as neuronal connectivity and receptor density, and of note is the high variability of brain size even in narrowly defined groups, for example children at the same age may have as much as a 50% differences in total brain volume.<ref name="Giedd2008">{{cite journal |last1=Giedd |first1=Jay N. |title=The Teen Brain: Insights from Neuroimaging |journal=Journal of Adolescent Health |date=April 2008 |volume=42 |issue=4 |pages=335–343 |doi=10.1016/j.jadohealth.2008.01.007 |pmid=18346658 }}</ref> Young girls have on average relative larger [[Hippocampus|hippocampal]] volume, whereas the [[amygdala]]e are larger in boys.<ref name="Kelly2007" /> However, multiple studies<ref name="Rabinowicz2002">{{cite journal |last1=Rabinowicz |first1=Theodore |last2=Petetot |first2=Jean MacDonald-Comber |last3=Gartside |first3=Peter S. |last4=Sheyn |first4=David |last5=Sheyn |first5=Tony |last6=de Courten-Myers |first6=Gabrielle M. |title=Structure of the Cerebral Cortex in Men and Women |journal=Journal of Neuropathology & Experimental Neurology |date=January 2002 |volume=61 |issue=1 |pages=46–57 |doi=10.1093/jnen/61.1.46 |id={{ProQuest|229729071}} |pmid=11829343 |s2cid=16815298 |doi-access=free }}</ref><ref name="L. Alonso-Nanclares2008">{{cite journal |last1=Alonso-Nanclares |first1=L. |last2=Gonzalez-Soriano |first2=J. |last3=Rodriguez |first3=J. R. |last4=DeFelipe |first4=J. |title=Gender differences in human cortical synaptic density |journal=Proceedings of the National Academy of Sciences of the United States of America |date=23 September 2008 |volume=105 |issue=38 |pages=14615–14619 |doi=10.1073/pnas.0803652105 |jstor=25464278 |pmid=18779570 |pmc=2567215 |bibcode=2008PNAS..10514615A |doi-access=free }}</ref> have found a higher synaptic density in males: a 2008 study reported that men had a significantly higher average synaptic density of 12.9 × 108 per cubic millimeter, whereas in women it was 8.6 × 108 per cubic millimeter, a 33% difference. Other studies have found an average of 4 billion more neurons in the male brain,<ref name="Pakkenberg & Gundersen1997">{{cite journal |last1=Pakkenberg |first1=Bente |last2=Gundersen |first2=Hans Jørgen G. |title=Neocortical neuron number in humans: Effect of sex and age |journal=Journal of Comparative Neurology |date=1997 |volume=384 |issue=2 |pages=312–320 |doi=10.1002/(SICI)1096-9861(19970728)384:2<312::AID-CNE10>3.0.CO;2-K |pmid=9215725 |s2cid=25706714 }}</ref> corroborating this difference, as each neuron has on average 7,000 synaptic connections to other neurons.
== Research Statistics ==
[[File:Yearly growth of the number of documents related to brain aging.jpg|thumb|Yearly growth of the number of documents related to brain aging in the CAS Content Collection.{{pmid|38095562}}]]
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, 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.


Significant dynamic changes in brain structure take place through adulthood and aging, with substantial variation between individuals. In later decades, men show greater volume loss in whole brain volume and in the [[frontal lobes]], and [[temporal lobes]], whereas in women there is increased volume loss in the [[Hippocampus|hippocampi]] and [[parietal lobes]].<ref name="Kelly2007" /> Men show a steeper decline in global gray matter volume, although in both sexes it varies by region with some areas exhibiting little or no age effect. Overall white matter volume does not appear to decline with age, although there is variation between brain regions.<ref>{{cite journal |last1=Good |first1=Catriona D. |last2=Johnsrude |first2=Ingrid S. |last3=Ashburner |first3=John |last4=Henson |first4=Richard N.A. |last5=Friston |first5=Karl J. |last6=Frackowiak |first6=Richard S.J. |title=A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains |journal=NeuroImage |date=July 2001 |volume=14 |issue=1 |pages=21–36 |doi=10.1006/nimg.2001.0786 |pmid=11525331 |s2cid=6392260 |url=http://pdfs.semanticscholar.org/1043/8bd0e1231dc8bf12ec3f407b5a6a7aa026c9.pdf |archive-url=https://web.archive.org/web/20201117094046/http://pdfs.semanticscholar.org/1043/8bd0e1231dc8bf12ec3f407b5a6a7aa026c9.pdf |url-status=dead |archive-date=2020-11-17 }}</ref>
== Further Reading ==
== Further Reading ==


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== See Also ==
== See Also ==


* [[Age-Related Diseases]]
* [[Skin Aging]]
* [[Hair Aging]]
* {{SeeWikipedia|Aging brain|}}
* {{SeeWikipedia|Aging brain|}}
== Todo ==
* https://www.psypost.org/new-neuroscience-research-reveals-the-remarkable-impact-of-exercise-on-brain-cells/#google_vignette


== References ==
== References ==
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<references />
<references />
 
[[Category:Aging]]
[[Category:Aging]]
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