Fit Fat: Lifelong Physical Activity Supports Healthy Aging By Improving Mitochondrial Function in Human Fat Tissue
While mitochondria are most often referenced for their critical role in cellular energy production, these cell structures also play a fundamental role in immune responses and the generation of reactive oxygen species (ROS) — complicated signaling molecules that need to be carefully regulated because excessive amounts can cause DNA and cellular damage. Impaired mitochondrial function in fat cells (adipocytes) has been associated with increased low-grade inflammation, altered metabolism, and excessive ROS production, culminating in accelerated aging. Exercise training has shown to have beneficial effects on mitochondrial health, but whether lifelong exercise training can sufficiently maintain mitochondrial function in fat tissue is currently unknown.
A research team from the University of Copenhagen in Denmark finds that mitochondrial energy production in the fat from lifelong highly exercise trained individuals outperforms that of young ones. Furthermore, ROS emission was generally lower in the fat tissue from lifelong highly exercise trained subjects than older untrained subjects. Taken together, while aging reduces intrinsic mitochondrial energy production in human fat tissue, lifelong high-volume exercise training increases mitochondrial function by increasing mitochondrial volume likely contributing to healthy aging.
"The group of older people who train most form less ROS and maintain functionality to eliminate it. Indeed, their mitochondria are better at managing waste produced in fat cells, which results in less damage. Therefore, exercise has a large effect on maintaining the health of fat tissue, and thereby probably keeping certain diseases at bay as well," says lead author and Assistant Professor Anders Gudiksen of the University of Copenhagen’s Department of Biology.
A Tale of Two of Adipo-cities
The human body has two different types of adipose tissue: white adipose tissue (WAT) that stores energy and brown adipose tissue (BAT) that dissipates energy as heat, “burning” fatty acids to maintain body temperature. WAT stores energy in big, oily droplets throughout the body. BAT, conversely, contains both smaller droplets and high amounts of mitochondria, which lend the tissue its chestnut color, and use these fatty droplets to generate heat.
"Overall health is closely linked with how well our fat tissue functions. In the past, we regarded fat as an energy depot. In fact, fat is an organ that interacts with other organs and can optimize metabolic function. Among other things, fat tissue releases substances that affect muscle and brain metabolism when we feel hungry and much more. So, it’s important that fat tissue works the way it should," explains Gudiksen.
Fitness Helps Mitochondria Fight on With Age
Exercise training improves mitochondrial health but whether lifelong exercise training can sufficiently maintain WAT mitochondrial function is currently unknown. Therefore, to dissect the role of lifelong exercise training on aging WAT, the Danish researchers recruited young and older untrained as well as moderately and highly exercise trained older male subjects. Study subjects were 20-32-year-old untrained men and 62-73-year-old men, who throughout their lives were either untrained, moderately trained, or highly trained. All men were healthy, unmedicated, and had a BMI below 30. From these participants, Gudiksen and colleagues took abdominal subcutaneous (s)WAT biopsies and blood samples to measure mitochondrial function and key metabolic factors in WAT and plasma.
The researchers assessed mitochondrial performance in the study’s participants, showing that mitochondria's ability to produce energy declines with age, regardless of how much a person exercises. "Although mitochondrial function decreases with age, we can see that a high level of lifelong exercise exerts a powerful compensatory effect. In the group of well-trained older men, fat cells are able to respire more than twice as much as in untrained older men," says Gudiksen.
The researchers can also see that the older volunteers who exercised the most throughout their lives have more mitochondria, which allows for higher respiration and, among other things, the release of more fat-related hormones that are vital for the body's energy balance. “Our results show that you can actually train your fat tissue to a very high degree – but that you needn’t cycle 200km a week to achieve a positive effect. What you shouldn't do, is do nothing at all," concludes Gudiksen, who hopes that researchers will pay more attention to what people can do to keep their adipose tissue healthy.
Is Fat the Key to Fewer Age-related Ailments?
According to the researchers, the study's findings are conservative because the participants are unlikely to represent the entire community, where a greater number of people are expected to be in poorer physical shape and suffer from health problems than those who were selected. Prescription medication was not used by any of the study's elder participants, despite the fact that a considerable majority of the population in this age bracket does.
The University of Copenhagen researchers' next step will be to look at where cellular damage happens when people don't exercise and what effect this has on the body as a whole over time. At the same time, the researchers are looking into ways to pharmacologically alter the mechanism in the mitochondria that transforms calories into heat rather than fat, minimizing the production of damaging ROS.
Gudiksen A, Qoqaj A, Ringholm S, Wojtaszewski J, Plomgaard P, Pilegaard H. Ameliorating effects of lifelong physical activity on healthy aging and mitochondrial function in human white adipose tissue. J Gerontol A Biol Sci Med Sci. 2021;glab356. doi:10.1093/gerona/glab356