The Prospects for a MicroRNA-Based Biomarker of Aging

The development of accurate and cheap biomarkers of biological age is an important goal for the research community. The issue at hand is this: short of sitting back and waiting for years or decades, how should one test a supposed rejuvenation treatment? How to evaluate whether it works and how successful it is? If you have to wait and see, as is presently the case, then even mouse studies take years and cost millions of dollars apiece. If you could instead wait a month and take some blood samples, then suddenly a whole lot more research can be accomplished with that money.

Consider proposed SENS treatments that involve the clearance of age-related cross-link compounds such as glucosepane that harm tissue flexibility and integrity, for example. It is clearly the case that researchers will be able to tell how well they achieve that immediate goal, as they will measure cross-link levels in tissues beforehand and afterwards - a simple and straightforward test of effectiveness. Researchers can also assess secondary measures that are considered important in aging and known to correlate with the presence of cross-links, such as blood pressure, blood vessel elasticity, skin elasticity, and so forth. In theory these should all improve; if not, well that would be an unexpected setback. But if it works, and all these measures move back towards the values typical of a youthful individual, is that actually rejuvenation? Has this patient's biological age been reduced?

At the moment that question is impossible to answer without sitting back and waiting for decades. One group of researchers is well on the way to demonstrating the reliable use of specific patterns of changing DNA methylation as a measure of biological age, however, and so far their methodology seems like a promising candidate for a biomarker of aging. Where there is one such measure, we should expect there to be others. Everything in our biochemistry interacts with everything else, after all. Thus here researchers make the first steps towards the possibility of assembling a biomarker of aging from some combination of circulating microRNA levels. It is quite intriguing that their research demonstrates patterns that are characteristic of age, yet independent of health status in the case of their chosen group of patients:

Circulating MicroRNAs as Easy-to-Measure Aging Biomarkers in Older Breast Cancer Patients: Correlation with Chronological Age but Not with Fitness/Frailty Status

MicroRNA's (miRNAs) are short, non-coding and highly stable RNA's that are involved in post-transcriptional regulation of gene expression. They are known as fine-tuning mediators of a wide variety of normal physiological pathways, developmental processes and pathological conditions; it is thus plausible that they also play a role in cellular senescence and tissue/body aging.

Circulating miRNAs actually are attractive candidate biomarkers for clinical use, because of their easy accessibility and outstanding stability in serum/plasma. Here, we describe the potential use of microRNA signatures expressed in serum/plasma for the assessment of biological age in breast cancer patients. We compared a panel of 175 different microRNAs, known to be among the most relevant in serum/plasma, between older and young breast cancer patients and validated the findings of this initial exploratory screening in an independent breast cancer cohort. At least 5 circulating microRNAs emerged from this study that are worth to be further explored as potential aging biomarkers in larger cohorts of young versus old fit versus old frail individuals, both within and beyond a cancer background.

Plasma levels of miR-20a-3p, miR-30b-5p, miR106b, miR191 and miR-301a were confirmed to show significant age-related decreases. The remaining miRNAs included in the validation study (miR-21, miR-210, miR-320b, miR-378, miR-423-5p, let-7d, miR-140-5p, miR-200c, miR-374a, miR376a) all showed similar trends as observed in the exploratory screening but these differences did not reach statistical significance. Interestingly, the age-associated miRNAs did not show differential expression between fit/healthy and non-fit/frail subjects within the older breast cancer cohort of the validation study and thus merit further investigation as true aging markers that not merely reflect frailty.

Comments

Should be a lot easier to examine microRNA levels than to sequence the entire epigemones of individuals.

It would be nice if there was an indicator that existed across mice and humans.

Posted by: jim at October 24th, 2014 8:29 AM

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