What causes the breakdown of brain structure and function with age?

After our 30’s and 40’s, our brains begin to reduce in size naturally by 0.5-1% a year [1], due to losses in shape, size and connectivity of the brain’s billions of nerve cell networks. This is a process called “neurodegeneration” and although it occurs gradually, it may be accelerated from many different factors throughout the lifespan.

These include alcoholism, heavy metal exposure, high fat/high cholesterol diets, smoking, stress, sleep disruption, use of certain prescription drugs, inflammatory health problems and other factors.

Nutrition plays an important role in regulating brain ageing [2]. For example, diets with higher levels of omega-3 fats have been reported to have a protective role in the brain, which preserves memory and cognitive ability [3]. On the other hand, diets higher in saturated fats appear to have the opposite effect [4].

What are some of the signs?

As mentioned, among the most notable changes that occur in older people are cognitive problems such as deficits in memory, problem solving skills, reasoning skills and slower communication [5]. Some medical problems that are associated with more extensive and irreversible memory loss, including dementia and Alzheimer’s disease. These increase in frequency after 70 years of age.

Older people start to develop emotional and behavioral problems, such as feelings of loneliness, depression and helplessness [6]. There are also mild losses of movement control and coordination (these are called “motor skills”), which is why older people are more likely to have falls. These are related to problems in regions of the brain where there is fine tuning of nerve signals in the muscles [7] combined with visual orientation.

What are the mechanisms of neurodegeneration?

• Oxidative stress: the brain is one of the most energy consuming and active organs in the body, so it can generate free radicals internally within the brain tissues. Ageing can increase the production of these factors [8].
• Inflammation: as the brain ages, it can also slowly develop a problem called “neuroinflammation”, where the internal immune system is activated, leading to problems with local blood vessels and low-grade damage [9].
• Sensescence: this is the name given to a complex process where cells “slow down” in their ability to work properly, divide and repair [10].

These processes interact with many others all working together in different ways, to create a very complex idea of how brain aging occurs [11]. It is believed that the natural changes that occur in the brain are progressive, and occur slowly throughout life, but increase towards the later decades.

One interesting connection that has arisen recently is the link between neurodegeneration and nutrition, via the “gut-brain axis” [12]. The gut microflora produces factors from foods we eat called “neurotransmitters”, similar to the chemicals used in the brain. But these bacteria also change with age, and respond to poor dietary choices such as lack of dietary fibre, lack of fresh fruit and vegetable variety and processed foods.

Some nutrients and natural substances that may help with brain ageing

The mechanisms above can be beneficially affected by making sure that we look after our diet, get a good variety of natural foods and maintain a balanced lifestyle. Some nutrients and natural substances have been identified to help with brain function, including:

Omega-3 DHA/EPA: these fats support neural networks and brain immunity to keep it working properly, and may counteract some ageing effects [13].

Vitamin D3: has similar actions to neurotransmitters in the brain [14].

Mushrooms: contain antioxidant compounds, vitamin D precursors, trace minerals and dietary fibre that may support the gut microflora and brain immune system

Bioactive herbs:

• Bacopa monnieri: known to have a stress reduction and cognitive enhancement affect on memory and concentration [15].
• Ginkgo biloba: known to have antioxidant and circulation boosting properties that may help with brain function and neuroprotection [16].

This is not a complete list, but we should remember that despite its complexity, the brain ages using the same biological processes as any other organs, so we should look after our whole body as we age.

References

1. Fjell, A.M. and K.B. Walhovd, Structural brain changes in aging: courses, causes and cognitive consequences. Rev Neurosci, 2010. 21(3): p. 187-221. doi: 10.1515/revneuro.2010.21.3.187.
2. Melzer, T.M., et al., In Pursuit of Healthy Aging: Effects of Nutrition on Brain Function. Int J Mol Sci., 2021. 22(9): p. 5026. doi: 10.3390/ijms22095026.
3. Mora, I., et al., Structured Long-Chain Omega-3 Fatty Acids for Improvement of Cognitive Function during Aging. Int J Mol Sci., 2022. 23(7): p. 3472. doi: 10.3390/ijms23073472.
4. Ruegsegger, G.N., et al., A meal enriched in saturated fat acutely impairs cognitive performance in obese men. Physiol Behav., 2022. 244:113664.(doi): p. 10.1016/j.physbeh.2021.113664. Epub 2021 Nov 27.
5. https://pubmed.ncbi.nlm.nih.gov/35430158/.
6. https://www.who.int/news-room/fact-sheets/detail/mental-health-of-older-adults.
7. Seidler, R.D., et al., Motor control and aging: links to age-related brain structural, functional, and biochemical effects. Neurosci Biobehav Rev., 2010. 34(5): p. 721-33. doi: 10.1016/j.neubiorev.2009.10.005. Epub 2009 Oct 20.
8. Sutkowy, P., et al., Physical Activity vs. Redox Balance in the Brain: Brain Health, Aging and Diseases. Antioxidants (Basel). 2021. 11(1): p. 95. doi: 10.3390/antiox11010095.
9. Tian, Z., X. Ji, and J. Liu, Neuroinflammation in Vascular Cognitive Impairment and Dementia: Current Evidence, Advances, and Prospects. Int J Mol Sci., 2022. 23(11): p. 6224. doi: 10.3390/ijms23116224.
10. Sahu, M.R., et al., Cellular senescence in the aging brain: A promising target for neurodegenerative diseases. Mech Ageing Dev., 2022. 204:111675.(doi): p. 10.1016/j.mad.2022.111675. Epub 2022 Apr 14.
11. Gonzales, M.M., et al., Biological aging processes underlying cognitive decline and neurodegenerative disease. J Clin Invest., 2022. 132(10): p. e158453. doi: 10.1172/JCI158453.
12. Alsegiani, A.S. and Z.A. Shah, The influence of gut microbiota alteration on age-related neuroinflammation and cognitive decline. Neural Regen Res., 2022. 17(11): p. 2407-2412. doi: 10.4103/1673-5374.335837.
13. Pawełczyk, T., et al., Omega-3 fatty acid supplementation may prevent loss of gray matter thickness in the left parieto-occipital cortex in first episode schizophrenia: A secondary outcome analysis of the OFFER randomized controlled study. Schizophr Res., 2018. 195:168-175.(doi): p. 10.1016/j.schres.2017.10.013. Epub 2017 Nov 2.
14. Bivona, G., et al., Serum Vitamin D as a Biomarker in Autoimmune, Psychiatric and Neurodegenerative Diseases. Diagnostics (Basel). 2022. 12(1): p. 130. doi: 10.3390/diagnostics12010130.
15. Simpson, T., M. Pase, and C. Stough, Bacopa monnieri as an Antioxidant Therapy to Reduce Oxidative Stress in the Aging Brain. Evid Based Complement Alternat Med, 2015. 2015:615384.(doi): p. 10.1155/2015/615384. Epub 2015 Aug 27.
16. Barbalho, S.M., et al., Ginkgo biloba in the Aging Process: A Narrative Review. Antioxidants (Basel). 2022. 11(3): p. 525. doi: 10.3390/antiox11030525.

from an Expert Author

George Thouas

BSc, MRepSc, PhD – Biomedical Scientist

George has worked as a medical researcher for 17 years in the university sector, at both Monash University health institutes, and The University of Melbourne. He spent 12 of those years in reproductive health and fertility research, in roles such as Clinical Research Associate, Clinical Embryologist, Post-graduate Demonstrator, Lecturer, and later as a Senior Research Fellow and Lab Manager. His doctoral thesis investigated the effects of mitochondrial damage in the oocyte. He also worked on improving the nutrient and growth requirements for in vitro fertilization and embryo development.

George has authored and coauthored more than 50 publications, including 1 book, 5 book chapters, 30 peer-reviewed journal reports and reviews, 6 patents, international scientific conference proceedings and health practitioner journal articles.

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