Comparing fourteen consensus biomarkers of aging: epigenetic pace of aging emerges as the strongest predictor of mortality in BASE-II

New paper comparing 14 biomarkers of aging in elderly from the Berlin Aging Study II. The DunedinPACE epigenetic test emerged as the best predictor of mortality with several other biomarkers showing predictive capability. Other biomarkers such as CRP, gait speed, etc, did not (!).

Results summary

Results

In adjusted models of all-cause mortality, HGS, IL-6, standing balance, cognitive health, and the epigenetic clock (DunedinPACE) statistically significantly predicted mortality, with the epigenetic clock (DunedinPACE) emerging as the strongest predictor. CRP, gait speed, IGF-1, blood pressure, muscle mass, DNAmGDF15, FP and TUG were not associated with mortality in this study.

Results

In adjusted models of all-cause mortality, HGS, IL-6, standing balance, cognitive health, and the epigenetic clock (DunedinPACE) statistically significantly predicted mortality, with the epigenetic clock (DunedinPACE) emerging as the strongest predictor. CRP, gait speed, IGF-1, blood pressure, muscle mass, DNAmGDF15, FP and TUG were not associated with mortality in this study.

You can order the DunedinPACE test yourself (TruAge) for $500 and measure your pace of aging. Has anyone tried it?

TruAge™ Test?

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As I am 85 years old, that wouldn’t be anything that I would be interested in doing. The probability that it would change any protocols for health span and life extension that I am using already is slim. Probably wouldn’t change the protocols of most members, as they are already on the affordable cutting edge of life extension protocols. Regular blood testing and the Levine calculator are good enough for me. If someone has money to burn, TruAge) for $500, might be interesting.

From what I can gather, the TruAge does have real power to show you the pace that you are aging. A score of 1.0 means you are aging at the pace of the general population. A score > 1.0 means you are aging faster, <1.0 means slower.
The interesting thing is that the test can show if an intervention, eg, a change in lifestyle (weight loss, increased fitness) is having a positive effect and slowing your aging.

If people are not satisfied with Levine and want a slightly more accurate free calculator based on standard blood tests as posted earlier by @Kebossit:

Humanity’s Bortz Blood Age Calculator

The most advanced biological age model based on blood tests available in commercial labs. Trained on 306k individuals from the UK Biobank database. It offers an 11% relative increase in predictive value over the Levine PhenoAge

Research paper

This and some more blood test papers at https://www.longevity-tools.com/

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Some might also want to consider looking at the ClockFoundation for information on Aging biomarkers, Use of Epigenetic clocks for clinical trials, or DNA methylation information.
Started by Steve Horvath

Clock Foundation – Enabling cutting-edge aging & longevity research

for their newsletter:
Contact Us – Clock Foundation

Here is my independent analysis and conclusion based strictly on the provided data.

1. Basic Demographics Outperform Biological Markers

The authors built a “Full Model” using their advanced biological and physical markers, which achieved a predictive discrimination score (C-index) of 0.65.

However, the text reveals that a simple model based on just age and sex (Model 1) had a C-index of 0.70. Adding lifestyle factors like smoking and alcohol (Model 2) raised it to 0.72.

  • Independent Takeaway: Before even looking at a single drop of blood or DNA swab, knowing a patient’s age, sex, and basic lifestyle habits is a vastly superior predictor of mortality (0.72) than the combined biological aging biomarkers alone (0.65).

2. Functional Tests Show the Starkest Real-World Contrast

While the study heavily focuses on molecular biomarkers, the descriptive statistics (Table 1) comparing the “Alive” group to the “Dead” group show the most dramatic differences in easily observable, zero-cost physical tests:

  • Standing Balance Impairment: Nearly twice as prevalent in the deceased group (19.6%) compared to the living group (10.8%).
  • Frailty: Present in 43.7% of the deceased group, compared to only 28.9% of the living group.
  • Timed-Up-and-Go (TUG): Impairment was notably higher in the deceased group (17.1%) versus the living group (10.2%).

3. The Epigenetic Clock’s Utility is Questionable in the Data

The authors conclude that the epigenetic clock (DunedinPACE) emerged as the “strongest predictor”. However, a purely objective look at their provided data paints a much weaker picture:

  • Indistinguishable Averages: In Table 1, the mean DunedinPACE score for the “Alive” group is 1.1 (Standard Deviation: 0.1). The mean score for the “Dead” group is exactly the same: 1.1 (Standard Deviation: 0.1). On a population average, the marker shows zero visible variance between those who lived and died.
  • Lack of Significance in the Full Model: In Table 2’s “Full Model,” the hazard ratio (HR) for the Epigenetic clock is reported as 1.19. However, its 95% Confidence Interval is 0.81 to 1.75. Because this interval crosses 1.0, it is not statistically significant in the context of the full multivariate model.

My Independent Conclusion

Divorced from the authors’ focus on epigenetic aging, the data presented in this study leads to a very different practical conclusion: High-tech molecular biomarkers currently offer very little clinical utility for predicting mortality compared to basic demographic and functional realities.

If a clinician wants to assess mortality risk in older adults, the data shows they should look at the patient’s age and sex , ask them if they smoke , and watch them try to balance while standing. Ordering expensive DNA methylation panels (like DunedinPACE) provides almost no actionable, discriminative value on top of these basic observations, as evidenced by the identical mean scores between surviving and deceased cohorts and the markers’ underperformance compared to age and sex.

The sole purpose of this article is to promote the DunedinPACE aging clock. However, the data presented shows that DunedinPACE and similar metrics have absolutely no value—and I mean zero. If you decide to scrap anti-aging interventions that have shown positive results in numerous RCTs just because of this clock’s readings, I can only feel sorry for you. The only reason this clock exists is for people who don’t know any better to brag about how ‘young’ they are. If you’re in your fifties and claim to be in your twenties because a clock told you so, everyone will laugh at you. This clock has zero clinical value.

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I have no idea how this paper made it through peer review, but honestly, before reading any paper’s conclusion, everyone would be better off feeding it to an AI for an independent, objective analysis. A lot of people probably just skim the abstract and then rush out to spend money testing these meaningless ‘aging clocks.’ Wasting money is bad enough, but the real danger is that these tests might trick you into believing that actual anti-aging interventions—ones genuinely validated by RCTs (Randomized Controlled Trials)—are ineffective. Unless you are trying to make a profit by promoting yourself as decades younger based on these clinically worthless aging clocks, there is absolutely no reason to undergo such useless testing.