Neurobiology of Aging

age, youth, contrast

In our mid-twenties, our physical performance peaks when mild cognitive decline begins. When we turn fifty, our eyesight worsens and in our sixties, we become more prone to disease and sickness. Our increased mental and physical vulnerability is rooted in biological and neuroscientific reasoning from the weakening of neural connections within the brain to the deterioration of the immune system. 

Cognitive Decline 

Our brain contains over one hundred billions neurons which are utilized to send information to the brain and elicit responses. Neurons are nerve cells, which act as the building blocks of the nervous system. At one end of the neuron is the dendrite, whose branching extensions receive messages and conduct impulses across the axon. Sometimes the axon is encased by a myelin sheath which is a fatty tissue layer that enables faster transmission speed. The resting potential of neurons is based on the fluid outside the axon’s membrane, which contains mostly positively charged ions, and the interior which has mostly negatively charged ions. 

When a stimulus causes a neural impulse, the neuron fires, opening the first section of the axon and allowing positive sodium ions to flood into the cell membrane. The ions are able to diffuse across the membrane because it is selectively permeable, meaning that smaller, nonpolar molecules can more readily cross the membrane than larger polar molecules. This is due to the phospholipid bilayer of the membrane, in which the hydrophilic heads face outward, while the hydrophobic tails of the fatty acid are in the center. The neuron cell membrane is selectively permeable to sodium ions, which enter through a sodium potassium pump in order to maintain a negative resting membrane potential by pumping 2 potassium ions back into the cell for every 3 sodium ions out of the cell simultaneously

Synaptic signaling is an example of local signaling of cells, during which an electrical signal triggers the secretion of neurotransmitters carrying chemical signals, which are diffused across the synapse. The synapse is the junction between neurons where neurotransmitters bind to receptor sites on the receiving neuron, exciting or inhibiting a neural impulse. As we age, our brain’s weakened connections between neurons leads to a reduced rate of communication. The brain’s capacity to transmit signals and communicate is decreased, while neural noise increases, meaning that there is a greater presence of random background activity in the brain signal. This can lead to confusion, weakened cognitive processing, and slower reaction time. 

The Brain 

Going from the cells that make up the brain, the larger parts of the brain that maintain particular functions are also affected by aging. The hippocampus is within the temporal lobe and plays an instrumental role in processing conscious memories and the brain’s ability to learn. The prefrontal cortex receives input from multiple regions of the brain to process information and contributes to executive function, higher cognition, planning, personality, and social behavior. Both of these parts of the brain serve an evolutionary purpose that has allowed for human survival. Through natural selection, the process in which individuals with certain inherited traits tend to survive and reproduce at higher rates than others, humans’ newer brains have evolved to allow for higher level cognition. The hippocampus is a homologous structure among vertebrae serving as evidence of common ancestry. The hippocampus is also a shared derived character among vertebrae as it is an evolutionary novelty unique to this group. 

These regions of the brain have high energetic demand which cannot be satisfied by aged cells. In order to produce usable energy, or ATP, cellular respiration must take place, during which glucose and oxygen are used to produce carbon dioxide, water, and ATP. For this process to occur, enzymes act as biological catalysts that facilitate the chemical reaction by lowering activation energy. After glycolysis and the krebs cycle, oxidative phosphorylation occurs in the inner mitochondrial membrane. During oxidative phosphorylation, an excited electron travels across an electron transport chain moving towards higher electronegativity, and establishing a proton gradient. Due to the proton gradient, the movement of hydrogen ions turns ATP synthase allowing ADP to be phosphorylated into ATP in the process of chemiosmosis. This process displays significantly lower respiratory capacities as we grow older. Age-related increases in oxidative damage have been observed in recent research, demonstrating the slowing down of cellular processes requiring energy in the aging body and brain. 

Hormones

As we age our endocrine system is also affected, impacting the concentration, metabolism, and function of hormones throughout the body. As controlled by the hypothalamus, hormones are products of the body’s endocrine system, whose glands secrete hormones as chemical messengers that travel through the bloodstream. Endocrine signaling is an example of long distance cellular signalling as hormones bind to cell surface receptors, triggering signal transduction pathways that activate particular transcription factors. As we age, the thyroid gland, which produces hormones that help control metabolism, slows over time. The parathyroid glands around the thyroid affect calcium and phosphate concentrations, which influence bone strength. Rising parathyroid hormone levels contribute to issues such as osteoporosis, which occurs when the body loses too much bone, making it far weaker.  

Diabetes also becomes more common as we age. According to MedlinePlus, the average fasting glucose level rises 6 to 14 milligrams per deciliter every 10 years after the age of 50. This is because the cells become less sensitive to the effects of insulin which are produced by pancreas. This process demonstrates a negative feedback system because when blood sugar rises, receptors in the body indicate to the pancreas that insulin must be secreted, lowering blood sugar levels to return to a normal state. 

Dementia 

As we age the deterioration of the proteins in our brains, alongside the weakening of the immune system leads to common forms of dementia, including Alzheimer’s disease. Acccording to the Alzheimer’s Association, more than 6 million Americans are living with Alzheimer’s and over 50% of adults over 85 are fighting against it. The disease is characterized by the accumulation of amyloid- beta in the brain, or misfolded proteins. Proteins are made up of amino acids which bind through covalent peptide bonds. In their primary structure, proteins are a chain of amino acids. In the secondary protein structure, hydrogen bonding of the peptide backbone causes folding into beta pleated sheets or alpha helices. From there, the protein reaches the tertiary structure where three dimensional folding is due to side chain interactions, until it is in the quaternary protein structure, consisting of more than one amino acid chain. Within an individual with Alzheimer’s disease is an accumulation of misfolded proteins, meaning that the proteins cannot function properly, such as in their role as enzymes. Also, the deterioration of the immune system causes stem cells to no longer be able to differentiate cells and replace damaged cells. As a result, stem cells cannot repair damaged cells in a brain afflicted with Alzheimers.

Genetics versus Lifestyle 

Both our genetics and our lifestyle influence the progression of our aging. On the one hand, our genes can predetermine much of our aging process, such as the shortening of telomeres with age. Telomeres are the specific DNA protein structures found at both ends of each chromosome. They play a vital role in preserving genetic information by protecting the chromosome’s genes from degradation and unnecessary repair. Shorter telomeres can lead to apoptosis, or programmed cell death, as well as an increased risk of disease. 

The rate of telomere shortening is largely influenced by lifestyle factors, including diet, sleep, stress management, and exercise. Regular physical activity can help with de-stressing, optimize neurobiological responses to stimuli, reduce inflammatory responses, and enhance growth factors. One important growth factor is brain-derived neurotrophic factor or BDNF. BDNF inhibits food intake and increases energy expenditure in the hypothalamus and promotes neurogenesis in the hippocampus, both of which improve cognitive function. Overall, exercise can increase metabolic and cardiovascular resilience, as well as increase insulin sensitivity and neuroplasticity: all of which tend to decline with age. 

Conclusion 

In the end, aging may be inevitable, but being aware of the neurobiological basis of its process allows us to predict vulnerabilities and counteract them with our lifestyles. At the same time, understanding the deterioration and changes within the body, allows researchers to learn more about cognitive decline and many of the diseases faced by the elderly, as well as ways to treat them. Regardless, the information on biological activities and the neuroscientific basis of the brain’s functioning combine to paint a picture and explain the process of human aging. 

Sources:

https://www.brainfacts.org/thinking-sensing-and-behaving/aging/2017/the-neurobiology-of-aging-012617

https://www.nature.com/articles/nrn3256

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142018/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868452/#:~:text=As%20the%20brain%20ages%2C%20its,activity%20in%20the%20brain%20signal.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834189/

https://medlineplus.gov/ency/article/004000.htm

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370421/

https://www.khanacademy.org/science/biology/cellular-respiration-and-fermentation/pyruvate-oxidation-and-the-citric-acid-cycle/v/krebs-citric-acid-cycle

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