Late to Evolve, Early to Decline - Exploring Human Brain Aging

Humans have a large, complex brain that has evolved over millions of years, supporting sophisticated behavior and advanced cognitive abilities. But does this remarkable brain come with a cost? A new study published in Science Advances suggests that the human brain is particularly vulnerable to aging, with the regions that developed most recently in our evolutionary history being the most susceptible.

Since We Parted Ways with the Chimpanzee

A new study aimed to address a complex evolutionary question: Which regions of the human brain underwent significant changes during the later stages of evolution, and are those regions more susceptible to aging-related processes? To identify brain regions uniquely developed in humans, researchers from the University of Düsseldorf  in Germany compared MRI scan datasets from 480 human brains and 189 chimpanzee brains—our closest evolutionary relatives.

The last common ancestor of humans and chimpanzees lived approximately six to eight million years ago, and we share about 99% of our DNA sequence with them. Since the two lineages diverged, the human brain has tripled in size, but its growth has not been uniform across all regions.

MRI scans provide high-resolution, non-invasive images of brain structures without causing harm to the subjects. In the initial stage of the study, comparing these images allowed researchers to identify the brain regions showing the most significant differences between humans and chimpanzees. These differences are believed to reflect the evolutionary changes in the human brain since our lineage diverged from that of chimpanzees. The most notable changes were found in the frontal lobe of the cerebral cortex, particularly in the prefrontal areas, which have undergone significant expansion in humans. These regions are linked to advanced cognitive functions, such as attention, decision-making, and problem-solving.

The image comparison helped researchers identify the brain regions with the greatest differences between humans and chimpanzees, as well as between chimpanzees and monkeys. Illustration showing the areas that have expanded most significantly among the different species | From the article Vickery et al., Science Advances 2024.

The Magic Touch

The researchers compared brain scans of humans and chimpanzees with those of two more distantly related monkey species, olive baboons (Papio anubis) and rhesus macaques (Macaca mulatta). This comparison enabled them to identify brain regions that developed later in the evolutionary history of the great ape group, which includes both humans and chimpanzees, compared to monkeys. The findings revealed that the parietal and frontal lobes, particularly regions involved in motor control and movement planning, were the most enlarged in chimpanzees compared to monkeys. This development likely allowed the ancestors of humans and chimpanzees to achieve greater control over hand movements.Indeed, in both humans and chimpanzees, this ability supports more delicate and precise actions than those observed in the monkey species studied. For example, chimpanzees demonstrate this skill by using tools, such as fishing for termites in narrow spaces with twigs.

In the second stage of the study, the researchers analyzed age-related differences between human and chimpanzee brains. MRI scans distinguish between gray matter, which contains nerve cells, and white matter, primarily consisting of nerve cell extensions that connect them. The researchers aimed to measure the reduction in gray matter, which reflects the rate of brain cell loss with aging in each species. This analysis included human subjects up to the age of 58 and chimpanzees up to the age of 50. To account for differences in lifespan, the researchers estimated that one human year is equivalent to 1.15 chimpanzee years. Older humans were not included to ensure the data remained comparable to the available chimpanzee samples.

Gray matter decreases with age in both humans and chimpanzees, but the reduction is uneven across brain regions. The illustration shows the decline in gray matter with age: the more yellow an area appears, the greater the reduction in gray matter. | From the article Vickery et al., Science Advances 2024.

The Brain in the Autumn of Life

The researchers observed that gray matter decreases with age in both humans and chimpanzees, though the reduction is not uniform across brain regions. In humans, the occipital lobe—responsible for sensory processing, particularly visual information—and regions involved in motor control retained more gray matter. In contrast, the frontal lobe, especially the prefrontal areas, showed the most significant loss of gray matter.

The study reveals that regions of the human brain that underwent more significant evolutionary changes are also the regions that experience the greatest gray matter reduction with aging. The researchers describe this as the "last in, first out" principle: brain regions that developed later in evolution are the first to deteriorate during aging. This pattern was not observed in chimpanzees. In their brains, the regions responsible for motor control, which underwent the most recent changes, show greater resistance to cell death. The researchers conclude that this phenomenon is unique to humans and does not represent a universal evolutionary principle.

One possible explanation is that the most vulnerable brain regions are densely packed with cells that have extensive projections and numerous synapses. These cells require significant energy, making them more prone to damage under stress.  Extensive neuronal cell death in these regions can contribute to cognitive decline and to development of neurodegenerative diseases, which become more prevalent in older age.

The study suggests that neuronal death begins many years before such diseases manifest. Similar studies have identified biomarkers in the blood that can be detected 10 to 20 years prior to the onset of neurodegenerative symptoms.  However, the brain appears to have compensatory mechanisms that help preserve cognitive abilities despite degeneration. For example, engaging in memory exercises and mentally stimulating activities can provide some protection against the effects of aging.