Fight Aging!

Researchers interested in finding genetic contributions to longevity generally start with some form of correlation study: trying to find commonalities between the genomes and epigenomes of long-lived individuals. So far, this has produced a great deal of data, much of which is unique to particular study populations - which suggests that there are many, many contributions to longevity buried in human genetic variations, and most are not all that important when considered in isolation. The odds of finding anything resembling a master switch for additional life span look remote at this point.

So the situation is complex, quite aside from the fact that it would still be a troublesome field of research even if the hunt was for one or more master switches. Researchers face an uphill struggle, as noted in a recent open access commentary, and thus have to be more inventive in their research:

It is a stroke of irony that lifespan - the principal phenotype used to search for aging genes - is a terrible phenotype for genetic analysis. Lifespan has relatively low heritability under most conditions, and it is affected by chronic, age-related diseases that confound its use as a biomarker of aging.

If the majority of aging genes are pleiotropic, as proposed by the evolutionary theory of aging, an opportunity is provided to identify these genes through the "back door," using phenotypes that are more amenable to genetic analysis.

To choose the pleiotropic phenotype for our studies, we went back more than 50 years to Williams, who, in his seminal paper, specified four "physiological expectations that follow from the theory," two of which we applied: "Rapid individual development should be correlated with rapid senescence," and, to specify a particular developmental phenotype, "The time of reproductive maturation should mark the onset of senescence." Therefore, to search for genes that regulate lifespan, we looked in the other direction - for genes that govern reproductive maturation.

The researchers then outline some of their investigations; when it produces candidate genetic variants, those variants still have to be confirmed in the same old standard, slow, and laborious way - animal studies of life span. In general the work of building a catalog of aging-related gene variants is slow going, and in the end will have far less practical application than other approaches to longevity science. This isn't to say that it shouldn't be done; all life science knowledge has value. But if the goal is to do something about the terrible cost of human aging, and do it as soon as possible, then approaches other than genetic investigation must have priority in the field.