Biomarkers of Aging at SAGE Crossroads
How do you determine a person's age from a biomedical perspective? Not how many years they have amassed, but to what degree has the body aged relative to some median measure. This is an important question in aging research and longevity engineering - if you have no measurable metric for age, then you can't know whether or not a supposed rejuvenation medicine is working, never mind how well it is working. So a great deal of time and energy has been devoted to establishing biomarkers of aging, and you'll find some discussion on this topic back in the Fight Aging! archives:
How can you rapidly determine that you have successfully developed an anti-aging technology that works in humans if you cannot tell how advanced the aging process is in any given individual, or if you cannot even agree on a working scientific definition for aging? Obviously you can wait around to count years and deaths, but that reliable fallback is not a good approach for those of us who would like to see working healthy life extension medicine in our lifetimes.
As I mentioned back then, I think that damage repair approaches to rejuvenation science - i.e. identify and then revert biochemical changes - sidestep some of these concerns. An array of specific identified biochemical changes (such as the forms of biochemical damage listed in the Strategies for Engineered Negligible Senesence) becomes the metric for aging, and you attempt to fix or revert every change you can identify until you can prove that any specific change is benign.
In any case, we are revisiting this topic today because the most recent batch of podcasts at SAGE Crossroads discuss biomarkers of aging. Head on over and take a look.
#44 - Biomarkers of Aging - Setting the stage: What are biomarkers of aging?
a biomarker is a way to measure a parameter in a biological system or subject. All of us have in our minds how old we are. We use it as we use a clock to count the passage of time. Over a human life, we measure the passage as months, years, decades and so on, but for medical purposes, if we are going to try to develop interventions that modify the rate of aging in individuals, first we have to find a way to validate measuring aging separate from chronological age. We know that not all 50 year olds are the same. The same for all 60 years olds or 80 years olds or any other age. People vary despite their same chronological age, so we have to have measures that get at how old a person really is biologically and how to measure that, and that’s how biomarkers come in.
it was a 10 year effort to try to find biological markers of aging that are different than chronological markers of aging. ... what we did was to create a very large colony of a variety of mice, inbred mice and inbred rats, as a source for studies looking for biomarkers of aging. ... All together of a 10 year span we had, if I remember right, 14 different laboratories involved and the biomarker research spanned the scientific spectrum from cellular and molecular model searches to whole organism behavior and sort of everything in between.
#46 - Biomarkers of Aging - Another perspective on the NIA research into the biology of aging
It’s been a very difficult process. The NIA ran a program for ten years back in the 1980s and 90s to try to identify such biomarkers and in fact was essentially not successful in that activity. The NIA invested a fair amount of money in this process, perhaps 20 million dollars, to come up with a panel of biomarkers and in the end did not come up with such and informative panel of biomarkers that could predict the chronological age of an individual within a species or the length of remaining life the individual could anticipate.
#47 - Biomarkers of Aging - What's holding the research community back?
[One stumbling block] is a lack of interest or a lack of research effort devoted to the topic. There have been major complicated human data sets where people have been tested for lots of different things, and there is some end point measure, whether they die, whether they get cancer, or whether they develop a hearing problem and so forth, and the data sets exist, but they haven’t really been evaluated by people who combine high class statistical skills and also a clear conceptual appreciation of the difference between a biomarker of aging and a risk factor for mortality.The other stumbling block is that data sets could be improved. If this were really the major goal of the project, you would want to measure in each person or each rodent, if it’s a rodent study, a batch of different kinds of changes. Changes in kidney function, liver function, cognitive function, skin composition, and gene expression. Highly enriched data sets of that sort would have to be prepared to provide the information needed for a high level evaluation of the biomarkers of the aging rate itself.
#48 - Biomarkers of Aging - How are we going to find biomarkers of aging?
It’s gone through various times of when it was a high priority and then given a lack of success in identifying biomarkers, it lost some its priority, but I see a resurgence now given what I said in response to the previous question that we are at an important state in gerontological research where there are specific interventions that can be evaluated....
There is a lot of extrapolation that can be done in terms of whether our success in pre-clinical studies will translate to clinical studies, but this can only be proven by the format that is accepted in the scientific world and that’s well-controlled clinical studies. These well-controlled clinical studies can only move forward when there’s consensus on what a biomarker of aging is and how it can be applied to such clinical studies.
It is an interesting topic, wherever your views may lie.