As measurements of biological age can fluctuate quite significantly, the question arises of whether biological age is truly a fixed number, or something capable of fluctuating throughout one’s lifetime. Recent reports of biological age reversal in particular disease states, such as diabetes mellitus, have shown promise as appropriate diabetic treatment effectively reduced biological age (6). Additionally, a methylation-supported diet and lifestyle change demonstrated up to an 11-year decrease in age, showing the significant potential for altering biological age (7). Given the intertwined nature of chronic stress and accelerated aging, Poganik et al. sought to investigate fluctuations in biological age, in both a murine model and using clinical data, to further elucidate the variability of biological age in response to a variety of physiological stressors (1,8).
In the mouse model experiments, parabiosis was used, in which two mice were surgically attached resulting in a shared circulatory system. This method has been previously shown to reduce DNA methylation age in murine models, and can provide insight as to how the circulatory system affects biological age (1). To evaluate interactions between blood and age, heterochronic (3 month old and 20 month old) mouse pairs were compared to isochronic (2 three-month-old mice) pairs. Mice were surgically attached and maintained for three months, after which point a subset was euthanized for analysis, and the other subset were surgically separated and allowed to recover for 2 months before euthanization and analysis. Additionally, to determine the impact of pregnancy on biological age, male and female mice were housed together and, after successful pregnancy and birth, pups were euthanized to allow the female mice to recover without needing to nurse (1).
In the human studies, DNA methylation data was obtained from blood samples, or from publicly available human methylation datasets. For the COVID-19 study, blood samples were obtained from individuals who were admitted to an intensive care unit in Boston, Massachusetts. These blood samples were centrifuged to derive a buffy coat from which DNA methylation profiling could be performed. To further elucidate whether physiological stress affects biological age, methylation data from pregnant patients, as well as patients undergoing elective and emergency surgery was obtained from the NCBI Gene Expression Omnibus (GEO), a publically funded genomics data repository, as well as from a few academic collaborators. In addition to the DNA methylation analysis, metabolite and gene expression profiling analysis was performed in a variety of different organs to provide additional data for determining biological age (1).