Metabolism, Aging and Longevity


 
Derek M. Huffman, PhD

At the most basic level, life is energy. Within each cell, the transformation of nutrients and oxygen powers the processes, activity and thoughts that make us living beings. The ultimate irony is that the metabolic miracle that makes life possible also generates byproducts that can damage DNA, accelerate aging, and eventually bring about its own end.

"Many factors are involved in aging, and most of them are not likely acting on their own. Some seem to be interacting, though we don't yet understand how they are talking to each other. In so many aspects of aging, metabolism plays a role, and that's where I'm seeing exciting targets for study that could lead to interventions that could slow or prevent some of the damage and diseases of aging," Derek M. Huffman, PhD, researcher at the Einstein Aging Center and assistant professor at the Albert Einstein College of Medicine said. He completed much of his training and early work in aging research at UAB in Birmingham.

"The top causes of disease-related mortality and morbidity in humans have one risk factor in common--aging," Huffman said. "The magnitude of risk in heart disease, cancer, COPD, Alzheimer's, Diabetes, Parkinson's, Arthritis and so many other health problems is also significant. LDL can triple your risk for heart disease. Age increases it a thousand fold.

"In the past, researchers have generally studied these serious health problems individually. Then the galvanizing realization was that all of these illnesses are diseases of aging. If we can attack the targets causing damage, we can help to find treatments for a whole range of conditions."

A primary target Huffman is studying is IGF-1 (Insulin-like Growth Factor). When the pituitary secretes human growth hormone, it travels through the blood stream to the liver and signals it to start producing IGF-1, which is then involved in building muscle, burning fat and supporting other body processes.

"IGF-1 is something of a paradox. In babies it is necessary for brain growth, and children need adequate levels to grow to their full potential. However, longevity studies show that people who live longer tend to have lower levels of IGF-1,"Huffman said. "We can also observe this in animals. Small dogs live longer than large dogs. Ponies live longer than large breeds of horses. We believe that because they are smaller, there is less hormone and less signaling activity in this pathway, which leaves their cells in better condition to maintain healthy function."

While YouTube is full of opposing videos telling you how to increase your IGF-1 level (body builders), or reduce it (vegans aiming for longevity), it would be wise to consider health history and current condition before attempting either.

"One of the goals of our research is determining the optimum dose of IGF-1 at each stage of life and in light of health status, history and genetic predispositions," Huffman said. "A diet to reduce levels in a child could put normal growth at risk, and a patient with cancer doesn't need to encourage the growth of damaged cells the body's defenses are trying to eliminate. We hope that learning more about the role of IGF-1 in growth and aging will enable us to develop medications to increase or reduce it as needed to help people live healthier as they live longer."

Huffman's colleagues are involved in two other research topics on the role of metabolism in aging.

"There have been numerous studies suggesting that calorie restriction could increase longevity," he said. "But then the question arose--could timing of feeding play a role? When mice on a calorie restricted diet are fed, they are hungry and eat quickly, which leaves a long period of fasting between feedings. During fasting, cells clear debris that could cause damage."

Work on autophagy won the 2016 Nobel Prize for Japanese researcher Yoshinori Ohsumi. Autophagy is a process that happens at the cellular level when cells shift from nutrient burning mode to clean up mode during fasting times between meals. The cells recycle debris, damaged proteins and even invading germs and break them down into amino acids or eliminate them. This could reduce damage to cells and tissues.

"Our researchers showed that dividing the daily calories into two feedings a day made animals healthier than those eating the same amount of calories, but without the fast," Huffman said.

In a parallel study at the Salk Institute, researchers found that even when given a less-than-healthy diet, mice whose eating time was restricted to 12 hours or less a day had less fat tissue, lower glucose and lipid levels, and higher muscle mass than mice with the same genetic background and same food who were allowed to eat around the clock. Metabolism seems to have its own circadian rhythm and there could be benefits in eating breakfast later and/or closing the kitchen early.

Researchers are also finding potential with nutrigenetics and nutrition. Although Vitamin D, magnesium and trace nutrients modulate hundreds of genetic and metabolic processes, the majority of people in the US have less than optimum levels in their bloodstream. In the past century, the shift away from fresh fruits and vegetables toward carbohydrates that can be mass produced and served as fast food has coincided with an increase in obesity and health problems related to aging.

The triage theory in nutrition research is investigating the premise that when essential nutrients are in short supply, the body prioritizes the processes we need right now to stay alive, and those we might need later to stay healthy, such as preventing damage to DNA, go lacking and may have a cumulative effect with the bill coming due in the diseases of aging.

Magnesium, Vitamin K and many of the important trace nutrients are found in dark green vegetables which are sparse in the American diet. A healthy bonus found in cruciferous vegetables is sulforaphane, which stimulates enzymes protective against cancer and other cellular damage. Raw broccoli is one of the richest sources, and 100 times as much is found in raw broccoli sprouts and shoots.

"The impetus for research into aging is not an aspiration to find the fountain of youth," Huffman said. "Years of decline and suffering from diseases that eventually kill us are rooted in aging. If we can compress the morbidity curve so that we can spend most of our years in good health and living to our full potential, that would make such a difference."

Search terms:

Metabolism, Aging and Longevity; Derek M. Huffman, PhD; Einstein Aging Center; Albert Einstein College of Medicine; IGF-1; Insulin-like Growth Factor; calorie restriction; autophagy; Yoshinori Ohsumi; Salk Institute

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