Metabolism & Basic Biology of Aging
Research in our Metabolism & Basic Biology of Aging directive focuses on understanding cellular and molecular processes that contribute to age-related diseases.
Scientists in this directive investigate a variety of factors including dietary components, physical activity, immune responses, intestinal homeostasis, the microbiome, cellular dysfunction, and senescence, and the key metabolic and molecular processes by which those factors impact age-related health.
Examples of our work
Research Summary: Metabolic Switch and Healthier Aging
Cellular senescence is a stress response that can contribute to a variety of age-related diseases, from cardiovascular disease to cancer. Our research in the Basic Biology of Aging directive led to the discovery of a specific fatty acid that activates a metabolic switch in senescent cells. Senescent cells have low levels of this fatty acid, which eliminates these cells if added back. Our scientists observed that when older mice are given this fatty acid they experience reductions in markers of senescence and signs of functional improvement. These findings indicate that manipulating levels of this naturally occurring fatty acid in the human body could promote healthier aging, and we are investigating its cellular mechanisms further.
Read our study on the metabolic switch that may promote healthier aging
Research Summary: Phytoene Can Help Protect Against Chronic Fatty Liver Disease
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), a form of chronic fatty liver disease, is a growing health problem in the United States, especially among people with obesity or diabetes. Scientists in our Metabolism & Basic Biology of Aging research directive discovered that phytoene, a precursor to lycopene found in substantial amounts in tomatoes and tomato products, could help protect against MASLD. In their study, mice fed a high-refined-carbohydrate diet developed less severe MASLD when given phytoene supplementation vs a control group that did not. The phytoene activated key proteins that help the liver burn excess fat for energy. These findings suggest that high consumption of phytoene, which is also more abundant in many golden-yellow-orange tomatoes than in red tomatoes, could help prevent or slow MASLD progression in high-risk individuals.
Additional studies
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Mobility declines with age, contributing to loss of independence and quality of life in older adults; but the biological drivers of this loss of function are largely unknown. Work in our Metabolism & Basic Biology of Aging directive explored the links between mobility declines in older adults and biomarkers of cellular senescence (a stress response that can contribute to a variety of age-related diseases), as part of a large clinical trial, conducted in part at the HNRCA. Our scientists found that several factors secreted by senescent cells were predictive of mobility loss, and that high levels of physical activity decreased both biomarkers of senescence and risk of disability. These results provide evidence of a link between senescence and mobility decline in older adults and identify physical activity as a possible mitigating intervention.
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Obesity remains a major public health challenge and understanding its underlying metabolic mechanisms is important to help address it. Work in our Metabolism & Basic Biology of Aging directive found that the enzyme acyl CoA synthetase 5 (ACSL5) produced in the small intestine, is involved in the development of diet-induced obesity. When we fed mice lacking the intestinal enzyme ACSL5 a diet that typically causes obesity, the mice did not become obese. They ate less of the diet because they had increased blood levels of the satiation hormones, glucagon-like peptide 1 and peptide yy, which are produced in the intestine. These findings suggest that targeting intestinal ACSL5 expression through dietary strategies may help protect against the development of obesity.
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The decline in gut function and metabolic health with age raises the risk of chronic diseases such as obesity and diabetes. While gut-based interventions can improve metabolism, it remains unclear how their effects differ and function between males and females. Work in our Metabolism & Basic Biology of Aging directive investigates gut function in aging by determining gut microbiota composition, gut barrier status, function of different gut cell types, and intestinal inflammation, and understanding how these factors influence body weight and glucose metabolism in male and female mice. This work aims to identify targeted gut-based interventions that can be translated to humans to maintain gut and whole-body health across the lifespan and prevent chronic metabolic disease onset.
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Many older adults experience appetite loss, which can lead to malnutrition and serious health complications. Unfortunately, in clinical practice, appetite loss is frequently unrecognized and therefore untreated. To better understand this issue, scientists in the Metabolism & Basic Biology of Aging directive conducted a systematic review of 58 studies to thoroughly summarize the available evidence regarding the relationship between appetite loss and adverse health outcomes in adults ≥ 65 years old. The review revealed older adults with appetite loss had a heightened risk for several negative health problems, especially malnutrition and mortality. These findings highlight a need for enhanced screening to detect and treat appetite loss in aging populations.
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Tryptophan hydroxylase (TPH) enzymes control serotonin production, which functions as a hormone and neurotransmitter. Two isoforms exist: TPH1, found in peripheral tissues, helps with energy balance, while TPH2, mainly in neural tissue, also appears in adipose tissue, where its role is unclear. Scientists in the Metabolism & Basic Biology of Aging directive discovered that mice lacking adipose tissue TPH2 became obese on a high fat diet, but did not develop obesity-related metabolic issues, like glucose intolerance or liver steatosis. Conversely, overexpression of TPH2 in adipose tissue led to obesity and metabolic problems in mice fed a standard diet. These findings suggest that inhibiting TPH2 activity in adipose tissue may help prevent metabolic dysfunction associated with obesity.
