March 30, 2024

Understanding science

Research Worth Sharing, March 2024 Edition

Organ-specific aging, a blood-based test for brain tumors, avoiding bananas in smoothies, stair-climbing tests for frailty, and omega-3 intake and CVD

Peter Attia

Read Time 4 minutes

AI analysis of plasma proteins for estimating the age of specific organs

Why we are interested: As Dr. Rich Miller recently discussed, we currently have limited biomarkers for tracking aging systemically and are virtually lacking organ-specific aging markers altogether. Accelerated organ aging contributes to disease, and development of methods to determine organ age could be valuable for predicting risk of specific diseases.

What the study showed: This study developed machine learning models to analyze plasma proteins originating from specific organs and assess their ability to predict organ-specific aging and disease. Accelerated aging in a single organ was reported in 20% of the study population, and organ-specific aging was associated with higher mortality risk and higher incidence of disease in the organ in question (e.g., brain age was strongly associated with Alzheimer’s disease and was useful in predicting the probability of dementia progression). Additionally, certain conditions, including heart attack and Alzheimer’s disease, were associated with accelerated aging in all organs.

doi: 10.1038/s41586-023-06802-1

A blood-based test for certain brain tumors

Why we are interested: Diagnosis of malignant tumors in the brain is a challenging process. Neural imaging can detect the presence of abnormal masses, but determining whether the mass is benign (as it is in most cases) or malignant typically requires a brain biopsy – a procedure with substantial risks depending on the site within the brain. Less invasive methods would therefore be highly likely to reduce complications involved in the process of diagnosing (or ruling out) brain cancer. The investigators behind this recent study report on such a non-invasive, blood-based method for detecting gliomas (malignancies of glial cells), which are the most prevalent type of brain tumors.

What the study showed: This study reports the performance characteristics of a blood-based test that detects malignant glial cells that have been shed by the primary tumor and have entered circulation. The test was initially validated using spiked control samples, from which it was found to have a sensitivity of 95% (95% CI: 83.1-99.4%) and a specificity of 100%(95% CI: 85.8-100%). Performance was then assessed based on real samples derived from patients across four study cohorts – which variously recruited healthy patients, patients with symptoms and/or observed lesions based on neuroimaging, or patients with known cancer of any type. Samples were analyzed in a blinded manner, and results showed high sensitivity (99.35%; 95% CI: 96.44-99.98%; n=154), specificity (100% (95% CI: 99.37-100%; n=588), and accuracy (99.87%; 95% CI: 99.25-100%; n=742). Though the test is not intended as a screening tool for healthy individuals, the authors propose its use as an alternative or supplement to brain biopsy for patients with abnormalities in neural imaging tests.

doi: 10.1002/ijc.34827

Compounds in bananas limit absorption of beneficial polyphenols from other fruits

Why we are interested: Fruits and vegetables are an essential part of a healthy diet, and as discussed in AMA #36, many studies have shown health benefits of specific plant-derived compounds. For instance, some research indicates that flavan-3-ols – a type of flavonoid and polyphenol found in cocoa, tea, and some fruits – may reduce the risk of cardiovascular death. However, combining certain compounds can interfere with their absorption and effects, so in order to derive maximal benefit from plant-derived compounds, we must be aware of and account for interactions such as the one investigated in this study.

What the study showed: In this single-blinded crossover study, eight men consumed either a capsule of cocoa extracta berry smoothie containing cocoa extract, or a banana smoothie containing cocoa extract. The flavan-3-ol bioavailability (from the cocoa extract) was assessed by measuring the level of flavan-3-ol metabolites in both plasma and urine. Absorption of flavan-3-ols was found to be inhibited when consumed with the banana smoothie but not the mixed berry smoothie, with peak flavan-3-ol metabolite levels demonstrating an 84% reduction with the banana smoothie. The effect was attributed to the banana smoothie having high polyphenol oxidase (PPO) activity, as this enzyme reacts with flavan-3-ols found in cocoa and other fruit polyphenols. So while bananas might be a tasty addition to smoothies, they may prevent you from getting the benefits of flavonoids found in chocolate or other fruits. 

doi: 10.1039/d3fo01599h

Old primates also have trouble climbing stairs

Why we are interested: Measures of subclinical frailty and motor competencies can be used to assess physical function and predict all-cause mortality, but no single motor function test is sensitive to all aspects of age-related functional decline. Thus, identifying new, simple tests that can accurately evaluate a range of functions improves overall physical assessments and health predictions, and given their close relationship to humans and relatively experimentally-friendly lifespans, non-human primates are an excellent model for such test development.

What the study showed: This study evaluated stair climbing speed as a metric for assessing aging-related physical decline before disease and loss of function occur. Compared to walking speed (a standard motor competency test), they found that stair climbing was better associated with chronological age (R= -0.68 vs. -0.45 for walking speed) and declined further with age, suggesting that stair climbing speed may be more effective as a method for detecting subclinical frailty. Of course, there’s no guarantee that the test would likewise outperform walking speed in humans (for whom walking quickly seems a far more natural skill than for the vervet monkeys used in this study), but regardless of whether stair climbing represents the best test for frailty, the important takeaway is that it might represent another tool to use in addition to other tests to obtain a fuller picture of functional decline.

doi: 10.1002/ajp.23582

Low omega-3 intake interacts with a family history to increase CVD risk

Why we are interested: Consuming higher levels of omega-3 fatty acids (EPA/DHA) has been shown to have a protective role against cardiovascular disease (CVD), but the role of EPA/DHA in modifying CVD risk associated with a family history of CVD is unknown. 

What the study showed: This study pooled the results from 15 observational studies (for a total of >40,000 adults without CVD), analyzed blood levels of EPA/DHA, and collected family history of CVD. The authors report a significant interaction between low EPA/DHA and family history of CVD, in which low EPA/DHA plus a family history was associated with a relative risk of 1.41 (95% CI: 1.30–1.54), higher than for either low EPA/DHA (RR=1.06; 95% CI: 0.98–1.14) or family history of CVD (RR=1.25; 95% CI: 1.16–1.33) alone. In other words, these results indicate that EPA/DHA is more protective among those with a family history than among the general population, providing greater motivation to emphasize intake of fish oil (EPA/DHA) as an important risk mitigation strategy for patients with family history of CVD.

doi: 10.1161/CIRCULATIONAHA.123.065530


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