In several of his articles, Ray discussed the non-specific “syndrome of being sick” -i.e. looking and feeling frail, while also being at high risk for virtually any condition, but without any of the specific symptoms/signs or diagnostic biomarkers of any specific condition. Ray said that Hans Selye linked this syndrome to chronic stress exposure, which Ray said ultimately leads to severe mitochondrial dysfunction and low oxidative metabolism. The study below now presents evidence that Ray was right (again!) and that declilne in mitochondrial number and activity can be used as a reliable prognostic biomarker for future frailty and chronic diseases. In addition, the degree of mitochondrial dysfunction apparently correlates with the severity of the “sick syndrome”, so it can also be used as a diagnostic tool for how severe an already established condition is. Aside from the well-known blood tests for pyruvate/lactate ratio, acetoacetate/hydroxybutyrate ratio, GSSG/GSH ratio, etc a simple tests for exhaled CO2 using a portable capnometer could probably be a very cheap and widely available, non-invasive method for diagnosing metabolic issues and thus future disease risk. In other words, as the study itself states, mitochondrial function reflects our “biological age” and it is biological age, and not chronological age, that drives frailty, diseases and aging itself. The good news here is that, unlike chronological age, biological age can be modulated so that we experience very little to none actual aging and disease.
https://pubmed.ncbi.nlm.nih.gov/38778912/
“…A recent study published in Frontiers in Cell and Developmental Biology, titled “Decreased mitochondrial respiration associates with frailty in community-dwelling older adults” (DOI: 10.3389/fcell.2024.1301433), presents a new perspective on how to diagnose and understand frailty in older adults, based on a cellular indicator: mitochondrial respiration in peripheral blood mononuclear cells (PBMCs). This work opens a promising pathway for the early detection of this geriatric syndrome, which affects a growing proportion of the aging population. The lead author is Gianella Liabeuf, then a student in the Doctorate in Nutrition and Food (DOCNUTAL) program, and it was developed by researchers from the Institute of Nutrition and Food Technology (INTA) at the University of Chile, in collaboration with the Faculty of Chemical and Pharmaceutical Sciences, the Faculty of Medicine at the University of Chile, the University of the Americas, the Bernardo O’Higgins University, and the Interuniversity Center for Healthy Aging. “Frailty corresponds to a greater susceptibility to negative health outcomes: for example, if a frail person becomes ill, it is more likely that the illness will be severe, unlike a robust person who is more likely to experience a milder illness,” explains Roberto Bravo-Sagua, a professor at INTA, PhD in Biochemistry, and one of the study’s authors. According to the researcher, cellular metabolism can act as a reflection of that robustness or frailty. “Cellular metabolism reflects our biological age. This means that we may have a certain chronological age (years of life), but our body may have a younger or older biological age. That is, our cells may be younger if we have experienced ‘successful’ aging, or more aged if we have been affected by negative factors.” The study was conducted in 58 older adults aged 70 and above, part of the ALEXANDROS cohort (a cohort under study for over 20 years at INTA, University of Chile), and revealed that frail individuals showed significantly lower mitochondrial oxygen consumption rates (OCR), particularly in men and in those over 80 years of age. “It’s true that frailty is traditionally easy to assess and does not require complex tests. However, this study opens the possibility of obtaining a new diagnostic parameter for frailty, with the potential of gaining predictive value. That is, to detect the early stages of frailty development before it manifests clinically.”
