What Happens to Our Brains as We Age?

Structurally, the brain shrinks as it ages. Studies suggest that brain shrinkage (scientifically termed brain atrophy) is due to the progressive death of brain cells. Some brain regions are more vulnerable to cell death and brain shrinkage than others; this varying degree of vulnerability partially explains why aging impacts some aspects of brain function more than others. 

The timing of normal age-related brain decline roughly coincides with that of other organ systems: Changes begin to occur around the third decade of life, with a notable acceleration after age 50. While there is an expected slowdown in brain function with aging, research indicates that those who develop mild cognitive impairment will experience more accelerated changes in the structure and function of the brain over time. In fact, the rate of brain atrophy during aging is believed to be predictive of future cognitive impairment and dementia.

So what influences the rate of atrophy? Genetics play a part, but environmental factors can also influence age-related decline. Aerobic exercise, for example, has been shown to increase the size of certain parts of the hippocampus, whereas excessive caloric intake and obesity can accelerate brain atrophy. 

Atrophy is one hallmark of an aging brain. We break down six others below: 

• Mitochondrial dysfunction
• Oxidative damage 
• Impaired energy metabolism
• Decreased hormetic responses
• A lack of neurogenesis
• Inflammation

As you may remember from 7th grade science class, mc are the “powerhouse” of the cells. Not only are they responsible for generating energy, but they're also responsible for sustaining cell survival. In the brain, they are distributed throughout the dendrites and axons of neurons, where they generate the ATP required to support neurotransmission, along with cell maintenance and repair. Most cell types in the brain experience progressive dysfunction of mitochondria during aging, which makes survival a challenge for aging neurons. 

As we age, neurons tend to accumulate dysfunctional proteins and mitochondria as a result of an oxidative imbalance – this occurs when there’s an increased production of reactive oxygen species (ROS) and/or reduced antioxidant defenses to balance them out. Normally, oxidatively-modified proteins and membranes are degraded and recycled. However, excessive oxidative stress can impair the function of unique systems that perform these roles, leading to an accumulation of damaged cellular structures as we age.

Similar to cellular structures such as proteins and cell membranes, the DNA in the brain cells is regularly damaged by ROS during the normal course of cellular function and aging. In healthy, young cells, damaged DNA is rapidly repaired by specialized proteins. However, reduced functions of these protective proteins can accelerate the aging process. For example, oxidative damage to DNA in some brain cells is believed to be responsible for the demyelination associated with a loss of white matter – which plays a critical role in helping the body process information – in the brain during aging. 

Over time, the metabolism of glucose and lipids is impaired in cells in the brain. As a result, our neurons' ability to increase glucose transport in response to insulin is compromised, leading to elevated glucose concentrations in the brain. This state – insulin resistance – is characterized by higher-than-normal fasting blood insulin and glucose levels, and is a major risk factor for diabetes, cardiovascular disease, and stroke. Peripheral insulin resistance is also associated with poorer cognitive function during aging. 

Neurons are continually subjected to many forms of cellular stress as a byproduct of their normal activity – and from environmental, physical and psychological challenges. Numerous signaling pathways have evolved to respond to cellular stresses. These responses include combating immediate stressors – anything from an infection to an attacker in an alley – alerting other cells to the stressor, and priming the body to prepare for future stressors or threats. Adaptive stress-response signaling pathways decrease in function as we age, thereby lowering the brain’s capacity to protect itself against stressors. Reduced protective mechanisms in the brain can leave neurons vulnerable to injury and neurodegenerative disorders. For example, signaling related to brain protective hormones such as Brain Derived Neurotrophic Factor (BDNF) – a key molecule involved in plastic changes related to learning and memory – is decreased in the aging brain. 

Neurogenesis is the process by which new neurons are formed in the brain. While the vast majority of neurons in the brain are produced during embryonic or early postnatal development, new hippocampal dentate gyrus granule neurons (brain cells that play a crucial role in learning and memory) and olfactory bulb interneurons (which send information about smells to the brain) are generated from neuronal stem cells (NSCs) in the adult brain. However, during aging, NSCs have a decreased ability to multiply and develop into functional neurons. Reduced neurogenesis is thought to contribute to age-related cognitive impairment and reduced plasticity – the ability of the brain to change and adapt over time – necessary for some types of brain repair. Oxidative stress, reduced DNA repair, and inflammation all contribute to age-related reductions in neurogenesis.

Similar to other organ systems, localized inflammation is a common aspect of brain aging. Supporting cells in the nervous system, specifically microglia, often exhibit an activated state in the aged brain that is characterized by changes in their shape and the production of proinflammatory cytokines (small proteins important in immune cell signaling). This dysregulated activation of innate immune responses likely contributes to – and results from – other aspects of brain aging described above. While dysregulated activation of immune cells contributes to brain aging and neurodegeneration, the same pathways, when properly regulated, play important roles in neuroplasticity and hormetic responses.

Cognitive change is a natural part of the aging process. Cognitive tasks, such as conceptual reasoning, memory, and processing speed all decline gradually as we age. To protect your brain as it ages, lifestyle choices play an important role: Diet, exercise, sleep, time with loved ones, mindfulness practices, and  the learning process are all demonstrated to help slow the aging process in the brain. Ensuring that your diet is rich in antioxidants can help alleviate oxidative stress and inflammation.  Vitamins, such as B6, B9, and B12, are crucial to generating the cellular energy required to support neurotransmission. Being mindful about your daily antioxidant and vitamin intake is a proactive way to care for and prepare and protect your brain as it ages.