The metric of ultimate success of multifactorial problems is often the wrong metric for tracking incremental progress or testing the importance of individual elements of overall solutions
Summary
Aging is multifactorial. It is several diverse and distinct molecular subproblems. Very effective treatment of aging will clearly require the intelligent combination of several elements (several separate therapeutic interventions). Many big, worthy problems humanity has accomplished were also multifactorial and required the combination of several separate solution elements (solutions to separate subproblems).
Lifespan and healthspan extension are the ultimate result of very effective comprehensive treatment of adult biological aging pathology. They are the obvious outcome metrics for any final or somewhat comprehensive solution to aging. However, that does not make them, or their surrogates, the right metrics for testing individual interventions or for tracking progress of the field.
In particular, this document makes 2 claims:
- Lifespan, healthspan, or their surrogates are not the appropriate way to test whether individual interventions will eventually play an important role in an overall suite of aging/longevity interventions.
- Lifespan, healthspan, or their surrogates are not the appropriate way to track progress of the field on the way to comprehensive, very-effective treatment for aging pathology.
Some implications of these claims are:
- The field should be less focused on lifespan studies of single interventions. Such studies should get less funding and less attention/press/sharing, relative to 4 other quite different things:
- science evaluating the efficacy of single interventions against specific subproblems of aging
- science finding, evaluating, and documenting the evidence for different subproblems being essential aspects of aging and drivers of multiple chronic diseases of aging (subproblems whose individual treatments themselves embody the geroscience hypothesis)
- science finding biomarkers/diagnostics quantifying subproblems of aging (as opposed to global surrogates for aging/lifespan/healthspan as a whole, aka estimates of “biological age” as a whole)
- tests of combinations of many interventions using lifespan, healthspan, or surrogates as endpoints
- The NIH’s ITP program’s results are not the right way to track progress of the field.
- (In a specific special case of the first bullet point above:) People should stop lamenting that no single intervention has yet beaten a decades-old severe calorie-restriction lifespan result in mice. This does not mean that there has been no progress in the field over those decades.
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