An Apparent Limit on the Quality of Longevity Therapies is Only a Statistical Artifact

Some time ago, statistical correlations in mortality data were used to suggest that interventions that reduce early mortality would lead to later accelerated aging. This view has become fairly widespread in aging theory, and we can see its echoes in studies that provide evidence for early physical prowess to correlate with faster aging, to pick one example. Not everyone agrees, however. Researchers here provide evidence to show that this relationship is an artifact of statistical methods, and there is thus no underlying physical basis for such an outcome. This in turn means that researchers should not be concerned in forging ahead to build therapies to reduce mortality at all ages.

The Strehler-Mildvan correlation was reported in 1960 in a now-famous and very well cited paper. It relates to the Mortality Rate Doubling Time (MRDT) and Initial Mortality Rate (IMR), two parameters of Gompertz mortality law. The original paper does not only introduce the empirical correlation, but also provides a sophisticated theory of aging behind it that is widely accepted among researchers. It says that if the mortality rate is reduced by any interventions at an earlier age, the MRDT goes down, i.e aging accelerates. This hypothesis leads to obstructions to the development of anti-aging therapies and makes optimal aging treatments impossible. Over years, quite a few researchers expressed doubts whether there was any biological meaning behind this correlation or not.

The Gero team prefers to use evidence based science approach over machine learning techniques for anti-aging therapies design, focused on physical reasoning behind mortality dependence on biologically available signals, ranging from gene expression to locomotor activity. Trying to determine physical processes behind Strehler-Mildvan correlation, the team noticed the fundamental disagreement between analytical considerations and possibility of SM correlation for Gompertz mortality law. They showed that SM correlation arises naturally as a degenerate manifold of Gompertz fit.

"We worked through the entire life histories of thousands of C.elegans that were genetically identical, and the results showed that this correlation was indeed a pure fitting artifact. The problem is not as complicated for worm experiments, though it gets pretty tough if humans are involved (the ratio of Gompertz slope to IMR is too large). Thus it seems like SM correlation is an artifactual property of the fit, applied in a limit where the fit does not work, rather than a biological fact. Elimination of Strehler-Mildvan correlation from theories of aging is good news, because if it was not just a negative correlation between Gompertz parameters, but a real dependence, it would have removed the potential for optimal anti-aging interventions and limited human possibilities for life extension."


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