Thanks for this great video Eleanor! You touch upon a really interesting point, which is the appropriateness of using an ageing clock when your the intervention involves changing a component of the same ageing clock. In this scenario, there is a need to choose an 'orthogonal' clock e.g. a clock whose biology is relatively distant from the intervention. For example, if you are changing CXCL9 levels (an intervention derived from the iAge proteomic clock), then choose a methylation based ageing clock as your readout. If your intervention is modifying a CpG site from a methylation clock, then choose a transcriptomic clock etc I'm really looking forward to your next clock video!
I recently took a saliva test to determine my biological age.As part of the process, I was asked my actual age, height, weight, and numerous questions about my health. The result of the test would have been more compelling if I didn't have to address issues that were not contained in my saliva. These questions created a "bias" that affected my confidence in this test,.
Great video! Yes, please continue with this topic. One idea: RELATIVE "RATE" OF AGING: The biological age is a "static point" on the chart. But what about the SLOPE of the B.A. relative to the C.A.? That tells us the RATE of aging compared to a typical person. Perhaps we could take samples from the patient at set time intervals apart for two comparative data points. (Couple weeks or months?) Also, if we tested both before and after a de-aging procedure, then we could measure the impact on the *pace* of aging, namely if it's slowing down or speeding up for that particular patient. Ideally, the goal is to get as close as possible to a plateau where the slope flattens out (like y=c) for a sort of asymptote. Therapeutics intended for impacting the aging rate could be measured for their proximity to a flat slope, and thus ranked. And, we should also look at aging *acceleration*.
Epigenetic clocks that use chronological age (CA) as an input value are like bicycles with training wheels. If it's truly objective, it would measure biological age independently - like the Uni Otago clock in Dunedin (NZ). An independent clock is the only true basis for measuring the efficacy of longevity interventions. And DNA methylation is only 1 possible biomarker that should probably be collated with other biomarkers (e.g. DEXA and Pulse Wave Velocity etc). It's convenient to think that a simple cheek swab will give you all the data you need, but it will probably take more biomarkers to provide an overall bio age score. The issue then is which biomarkers to select and what weightage to assign each. Some combintation of human intelligence and AI is probably required to solve this riddle.
What are your thoughts on the “phenotypic aging clocks” that use common blood bio markers? The one I am familiar with is the Levine Phenotypic Age calculator.
Considering Aubrey de Grey's classification of the different areas of damage in humans caused by aging. (seven areas, I believe) It seems logical and helpful to develop a "clock" that measures the progression of each of these areas. Yes, the best outcome would be to have one clock to rule them all. :). but in the absence of this, relating the clocks to recognized classification of aging would give an indication of which of the areas one might want to concentrate on.
Excellent point! To add to that, with such a collection of data, we might then want to create new forms of composite health summaries, like the H-index used in peer-review.
If biological age is different from chronological age, why use still numbers that recall the usual sense of age that we have? Having a biological age of 5 years less then my chronological age, has no real information for me. I would use another scale, for excample: let's define the best level this markers can be as 100% youth, and 0% the marker's level of people that have just died. So, after a biological test, i would get as a response: you are 70% youth. That would make sense to me.
Great video, as always, super informative. I know you couldn't cover them all, but I'm a bit surprised there is no mention of causal clocks like ru-vid.com/video/%D0%B2%D0%B8%D0%B4%D0%B5%D0%BE-TGcSwVjFdXc.html which addresses one of the challenges mentioned at the end.