Dunedin Pace of Aging Clock Responds to Lifestyle Interventions
Aging clocks cannot be trusted to produce useful data for any novel intervention in aging. They are produced via machine learning approaches applied to biological data from a large study population, and there is very little understanding of how underlying mechanisms of aging connect to the data used to build the clock. Thus effects on aging produced by way to change mitochondrial function or clear senescent cells may or may not be accurately reflected by any given clock - the only way to find out is to run a lengthy, expensive life span study, which defeats the point of having a quick and simple measure. The only practical way forward to make clocks more trustworthy in the near term, or at least to understand which clocks are most consistent, is to gather as much data as possible on their responses to interventions known to at least modestly impact aspects of aging, and that is exactly what is happening.
Aging-related chronic diseases are driven by multiple mechanisms, motivating efforts to develop feasible interventions that can attenuate biological aging. DNA methylation-based epigenetic clocks, particularly measures of the pace of aging such as DunedinPACE, are sensitive to relatively short-term changes in aging processes. However, evidence from randomized controlled trials remains limited. We conducted a randomized controlled trial to test a 12-week multimodal lifestyle intervention comprising exercise and dietary guidance involving daily consumption of yogurt containing Bifidobacterium longum BB536 on DNA methylation-based aging measures in overweight men aged ≥50 years.
The intervention group exhibited a significant deceleration in DunedinPACE, corresponding to an estimated 2.2% slower pace of aging, whereas no meaningful change was observed in the control group. Exploratory analyses further identified a significant reduction in DNAmCystatinC, a renal-related GrimAge surrogate marker, while no clock within the biological age remained significant after false discovery rate correction. These findings suggest that a feasible, multimodal lifestyle intervention-including exercise and dietary guidance with daily consumption of yogurt containing Bifidobacterium longum BB536-may be associated with short-term changes in selected DNA methylation-based aging measures. Larger and longer-term studies are warranted to confirm the durability and clinical relevance.
I think the Conboy "Noise Barometer" clock is probably useful. They looked at methylation of very tightly controlled genes and used the variance of those as a clock.
As you said, the other clocks don't detect disease so are not very useful.
"We established that dysregulation of such cytosines, measured as the sums of standard deviations of their methylation values, quantifies biological noise, which in our hypothesis is a biomarker of aging and disease. We term this approach a "noise barometer""
https://pubmed.ncbi.nlm.nih.gov/37702598/