New Study Reveals Running Can Protect Against Brain Aging

Middle-aged mice that ran on a regular basis maintained the connectivity of their adult-born neurons, providing new insight into the potential protective role of exercise against memory decline and neurodegeneration as we age.

Key Points:

Exercise in midlife increases the number of adult-born neurons in the hippocampus, a brain region essential for learning and memory.
Old, adult-born neurons in the hippocampus have their connections strengthened by running, making them more effective for certain types of learning and memory.
As a whole, consistent running during middle age may improve contextual and spatial memory by rewiring the network of mature neurons.

Running preserves the wiring of neurons involved in memory during aging in mice, according to new research. Long-term running significantly increases the input from newly formed neurons onto “old” adult-born neurons, preventing the loss of adult-born neurons in regions of the brain crucial for contextual and spatial memory. Researchers from Florida Atlantic University, the National Institute on Aging (NIA), and the Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV) in Mexico City conducted this study, which demonstrates how long-term exercise benefits the aging brain profoundly.

What Effects Does Exercise Have On The Aging Brain?

The hippocampus and the outer layer of the brain (the cortex) are crucial for all types of learning and memory, but they are among the first brain regions to show signs of aging, leading to cognitive decline as we get older.

One early indicator of damage to these brain areas and the neural pathways connecting them is a decline in “pattern separation”—the ability to distinguish between events and stimuli that are superficially similar. The capacity for pattern separation relies on the development of new neurons in adulthood (adult neurogenesis). When adult neurogenesis in the hippocampus slows or stops entirely, the size of the hippocampus decreases, and the strength of the connections between the hippocampus and other brain regions involved in learning and memory deteriorates.

More and more evidence suggests that physical activity can halt or even reverse these structural and functional declines in the elderly. It has been demonstrated that regular exercise reduces inflammation in the hippocampus and increases blood flow and growth factors in that region. Adult neurogenesis in the hippocampus of rodents has also been shown to be significantly boosted by running, which aids in the preservation of spatial memory as one ages. However, it is still unclear if and how exercise influences the connectivity of these adult-born neurons over time.

Running Increases Number of Hippocampal Neurons and Their Connections

This research demonstrates that maintaining physical activity from early adulthood into middle age helps preserve and even strengthen the network of connections between neurons that develop in the adult brain. There are two major phenomena at work here. First, mice that consistently exercise during midlife have a higher number of hippocampus neurons that are born as adults and survive into old age. Second, hippocampal cells have increased connectivity, both between subhippocampal regions and to regions beyond the hippocampus.

**(Vivar et al., 2023 | *eNeuro*)** **Running increases adult-born neuron survival and connectivity in middle-aged mice.** (A) Adult young mice (1.5 months old) were injected with a green dye that labeled the nucleus of neurons in the dentate gyrus, a known site for neuron generation, and then housed for six to nine months in either control (B) or voluntary running conditions (C). Six months later, they were given a second set of injections containing a magenta dye that would be used to trace the cell projections of cells in the dentate gyrus. Cells labeled with both dyes are yellow, indicating the number of old cells that survived and have network connections.

The study’s authors show that chronic running enhances communication between new neurons born in the hippocampus during early adulthood and the various types of neurons already present there. Running, for instance, strengthens connections between adult-born hippocampal neurons and interneurons, both of which are critical for preserving the encoding of episodic memories as we get older. This increased connectivity of old adult-born neurons may help preserve network activity in old age, which in turn may improve memory.

The researchers also noted drastic shifts in the cortical inputs received by the hippocampus’s mature, naturally-born adult neurons. When compared to their sedentary counterparts, runners’ brains continue to receive input from the perirhinal cortex, a region crucial to object recognition. Runners also had an increase in and shift in the relative contribution of the various entorhinal cortices to the network of mature, adult-born neurons, which are responsible for memory, navigation, and the perception of time. The entorhinal regions’ contributions increase and shift under running conditions in a way that improves the integration of spatial and contextual information, which may slow or prevent age-related memory decline.

**(Vivar et al., 2023 | *eNeuro*)** **Running during middle age increases the connectivity of cortical regions to adult-born neurons in the hippocampus. (**A) Schematic representation of the cortical input areas in a horizontal slice. (B) Inputs from the perirhinal cortex (PRh), a region crucial to object recognition, to adult-born neurons are only present in RUN mice. (C) Running increases the total number of traced cells in the entorhinal cortex (EC), a widespread network hub for memory, navigation, and the perception of time.

Taken together, these results suggest that regular long-distance running can delay the loss of memory associated with aging by improving the network connectivity among the adult-born neurons that are born in early adulthood and encouraging their participation in cognitive processes. The authors propose that regular running may help the aging brain maintain some of its plasticity by stimulating the growth of new connections between the brain’s existing neurons.

This research highlights the importance of making exercise a regular part of our lives by shedding light on how it can help preserve memory function as we age, beginning in our younger adult years and continuing through midlife.

A major limitation of this study is the absence of experiments that tie together how these increased inputs and cell numbers affect brain activity and the behavioral abilities of the mice. In spite of the fact that this study only examines the connections between adult-born neurons, its authors believe their findings provide valuable insight into the broader effects of running on the brain and how physical activity can preserve cognitive abilities in later life.