Stanford Scientists Uncover New Indicators of Health, Disease, and Aging

Stanford Scientists Discover Novel Insights into Health, Disease, and Aging

The human lipidome, encompassing the full array of lipids in the body, is gaining prominence for its pivotal role in human physiology. Particularly, it has come under scrutiny for its direct susceptibility to dietary influences and the presence of gut microbes. Furthermore, it holds immense potential in the realm of disease intervention, with a specific focus on conditions like Type 2 diabetes. A recent comprehensive study delves deep into the lipidome, shedding light on its associations with key health indicators such as insulin resistance, aging, and responses to infections. Moreover, it unveils its potential as a tool for predicting biological aging and guiding interventions to enhance health.

The sequencing of the human genome was once thought to herald a medical revolution. However, scientists soon realized that possessing a genetic blueprint alone is insufficient to comprehend the intricate workings of the human body in action. This necessitated a deeper understanding of the proteome, encompassing all the proteins expressed by our genes, which form the cellular machinery responsible for executing the majority of bodily functions. Now, another class of molecules known as the lipidome, encompassing all the lipids within our bodies, is providing further insights into human physiology.

Lipids comprise a broad category of small, fatty, or oily molecules, including triglycerides, cholesterol, hormones, and certain vitamins. In the human body, they serve crucial functions, constituting cell membranes, acting as cellular messengers, storing energy, and playing pivotal roles in responding to infections and regulating metabolism.

Unlike our genome, which remains essentially stable, and our proteome, which, though influenced by health and environmental factors, is largely dependent on genetic encoding, our lipidome can be directly influenced, in part, by our dietary choices and the composition of the microbiota residing in our gut. This characteristic makes it more adaptable and potentially more responsive to interventions. However, the sheer number and diversity of lipid molecules—numbering in the thousands—have posed challenges to their study.

Michael Snyder, PhD, the Stanford W. Ascherman, MD, FACS Professor in Genetics, aptly summarizes the situation by stating, “Lipids are very understudied. They are involved in pretty much everything, but because they’re so heterogeneous, and there are so many of them, we probably don’t know what most lipids really do.”

In a groundbreaking study from Snyder’s lab, published in Nature Metabolism on September 11, 2023, researchers have embarked on a comprehensive exploration of the human lipidome. They have meticulously tracked its transformations under both healthy and diseased conditions, with a particular emphasis on the development of Type 2 diabetes.

Key Health Indicators

Over 100 participants, including many at risk for diabetes, were observed over a span of up to 9 years. They provided blood samples every three months when in good health and more frequently during illness. Employing mass spectrometry techniques, which segregate compounds based on molecular mass and electric charge, researchers cataloged approximately 800 lipids and their correlations with insulin resistance, viral infections, aging, and more.

The findings of the study revealed that although each individual’s lipidome boasts a distinctive signature that remains consistent over time, specific types of lipids exhibit predictable alterations in response to a person’s health status.

For instance, more than half of the cataloged lipids displayed associations with insulin resistance, a condition where the body’s cells fail to efficiently use insulin to absorb glucose from the bloodstream, often leading to Type 2 diabetes. While insulin resistance can be diagnosed by measuring blood glucose levels, comprehending the changes in the lipidome offers insights into the underlying biological processes at play.

Daniel Hornburg, Ph.D., a former post-doctoral scholar in Snyder’s lab and co-lead author of the study, emphasizes the significance of these findings, stating, “Every molecule that is associated with a disease has a chance of telling us more about the mechanism and may be serving as a target for affecting the disease progression.”

Researchers also identified over 200 lipids that undergo fluctuations during a respiratory viral infection. The oscillations in the levels of these lipids corresponded to heightened energy metabolism and inflammation during the early stages of infection, potentially indicating the trajectory of the disease. Interestingly, individuals with insulin resistance exhibited some anomalies in their response to infection and a weaker reaction to vaccinations.

Aging Dynamics

The study’s wide range of participants, spanning from 20 to 79 years of age, coupled with the extended duration of the research, allowed scientists to observe how the lipidome evolves with aging. The results demonstrated that most lipids, including cholesterol, increase with age, while a select few, notably omega-3 fatty acids renowned for their health benefits, decrease. Furthermore, these signs of aging in the lipidome do not manifest at the same rate for everyone, with insulin resistance appearing to accelerate the process.

Si Wu, PhD, co-lead author of the study and another former postdoc in Snyder’s lab, raises the intriguing prospect that lipid profiles could potentially predict whether an individual is undergoing biological aging at an accelerated or decelerated pace.

An unexpected revelation from the study was the consistent association of certain groups of lipids, such as ether-linked phosphatidylethanolamines, which are believed to possess antioxidant properties and participate in cell signaling, with better health. These lipids may emerge as candidates for novel methods of health monitoring or even as dietary supplements.

Moving forward, Snyder’s lab aims to delve deeper into specific lipid correlations with lifestyle changes, paving the way for further insights into the intricate interplay between lipids and human health.

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More about Lipidome Impact

• Nature Metabolism: “Dynamic lipidome alterations associated with human health, disease and ageing”