A significant percentage of preclinical research is devoted to finding treatments or cures, but several recent studies with mice have gone beyond finding a cure for a specific disease or condition, venturing into the realm of enabling humans to age better and live longer.
While numerous studies have pointed to general lifestyle factors that can influence lifespan, such as diet, exercise, and sleep quality, recent research has been getting more granular, exploring specific brain cells, proteins, and amino acids that may hold the key to prolonging human life.
Improving a Communication Pathway Between Brain and Fat Cells
A new study from Washington University School of Medicine in St. Louis has identified a key communication pathway between the brain and the body’s fat tissue that influences aging in mice.
The team identified a specific feedback loop as central to energy production. As we age, we lose energy, and the gradual deterioration of this communication pathway may be to blame.
The researchers discovered a group of neurons in the brain’s dorsomedial hypothalamus that signal fat tissue to release energy. The neurons release a protein called Ppp1r17 that, when present in the nucleus, activates neurons and stimulates the sympathetic nervous system, which controls the body’s fight or flight response.
During this response, neurons in the hypothalamus initiate a series of events that activate neurons controlling white adipose tissue—a type of fat stored beneath the skin and around the abdomen. This activated fat tissue releases fatty acids into the bloodstream to fuel physical activity. Additionally, the fat tissue releases a crucial protein, the enzyme eNAMPT, which travels back to the hypothalamus, enabling the brain to generate the energy it needs to function.
This feedback loop weakens with age, with Ppp1r17 often leaving the neuron’s nucleus. To counteract this effect, the researchers genetically altered mice to keep the targeted pathway active beyond a certain age.
They discovered that the modified mice were more active, showed signs of slower aging, and looked healthier, with thicker and shinier coats. They also lived longer—approximately 60–70 days longer than the control mice, representing an increase in lifespan of about 7%.
The findings of the study may hold promise for an anti-aging therapy in humans that involves eNAMPT in various ways.
Blocking a Certain Protein
Researchers at Duke–NUS Medical School in Singapore, Imperial College London, and MRC Laboratory of Medical Sciences have extended the lifespan of mice by around 25% by blocking interleukin-11, a protein that promotes inflammation and has been tied to aging processes in human cells.
To test the efficacy of blocking interleukin-11, the team injected 17-month-old mice (about the equivalent of 55 human years) with an antibody that blocks its action. The mice, which received injections every three weeks, lived 20%–25% longer than mice that did not receive the injections.
The treated mice also stayed healthier longer—with lower cholesterol and body weight, stronger muscles, and better liver function and metabolism. In addition, they seemed to be more resistant to cancer—16% of the treated mice developed cancer, compared to 61% of the untreated mice.
This indicates that targeting IL-11 may offer a promising strategy for addressing the adverse health effects of aging in humans.
Limiting a Specific Amino Acid
Isoleucine is an essential amino acid, but a new study has found that too much is linked to lower metabolic health and a higher body mass index (BMI).
Isoleucine is used to build protein, and must be obtained from external sources like eggs, meat, and soy because the body can’t make it from scratch. But people who consume too much of it tend to be overweight.
In a recent study at the University of Wisconsin-Madison, researchers explored the effects of isoleucine using three groups of mice. The control group was fed a diet containing 20 common amino acids. The second group consumed the same combination of amino acids, reduced by about two-thirds. In the third group, only the isoleucine was reduced by two-thirds.
The mice with restricted isoleucine intake showed both an extended lifespan and better health, with reduced frailty, better muscle strength, leaner body composition, greater endurance, and lower blood sugar. Males lived 33% longer, and females 7% longer. Despite eating more, they burned more energy and stayed lean without increased activity.
The results indicate that limiting isoleucine in humans, either through diet or medication, could produce similar anti-aging benefits.
