Klotho and the Age Window
Fabrisia Ambrosio co-authored a 2021 eLife study showing that systemic Klotho overexpression improved muscle strength in old mice but produced no functional improvement in oldest-old mice, with the boundary linked to an entropy inflection point in aging-hallmark genes.
Klotho improved muscle strength in old mice. In oldest-old mice, it did not, even though gene expression changed in both groups.
Fabrisia Ambrosio, from the University of Pittsburgh's Department of Physical Medicine and Rehabilitation and the McGowan Institute for Regenerative Medicine, co-authored the paper (eLife, 2021, doi: 10.7554/eLife.61138, 49 citations). The team used a statistical physics framework: they estimated network entropy across aging-hallmark genes to quantify molecular disorder in muscle tissue. Entropy reached an inflection point at old age. Systemic Klotho overexpression via AAV (adeno-associated virus) altered gene expression in both age groups, but for many genes the direction of change was age-dependent. Strength improved only in old mice; beyond the entropy inflection point, no functional improvement was observed.
Three co-authors are from Boehringer Ingelheim's Research Beyond Borders / Regenerative Medicine division: Joerg D. Hoeck, Sebastian Kreuz, and Michael Franti.
In this study, Klotho's functional effect was age-dependent. "Does Klotho work?" is an incomplete question without specifying age.
🔗 Paper in eLife · Ambrosio's profile in Eternal Search
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The biphasic and age-dependent impact of klotho on hallmarks of ...
The edge connects a researcher to a specific eLife paper that quantifies an age-dependent efficacy window for Klotho in skeletal muscle aging, with pharmaceutical co-authorship from Boehringer Ingelheim, offering substantive insight for anyone tracking longevity intervention research and the conditions under which molecular interventions stop working.