## Jeanne Calment's Secret?

The story of Jeanne Calment, as the oldest verified human, represents an intriguing case for longevity practitioners, and serves as something of a cautionary tale for those in the annuity and pensions space. At age 90, she exchanged ownership of her apartment upon her death for a lifetime annuity of 2500 francs per month. The lawyer paying her annuity, Andre-Francois Raffray died of cancer in 1995 and left his family to continue payment. Calment survived a further two years before dying of natural causes aged 122.

It seems obvious that longevity has a substantial genetic component, but that doesn't mean such a component will prove simple to isolate. Late last year an ambitious attempt to map the genome of a group of so-called supercentenarians, survivors beyond the age of 110, "found no significant evidence of enrichment for a single rare protein-altering variant or for a gene harboring different rare protein altering variants in supercentenarian compared to control genomes.". This was a small study, although when you are dealing with supercentenarians, that goes with the territory.

This wasn't the first research to consider longevity by examining an unusually long-lived population. Ongoing studies consider, for example, both the Ashkenazi Jewish and Okinawan populations and such work continues to generate useful insights. Last week however, we appear to have taken a step towards understanding Jeanne Calment's case, not by studying populations we expect to live long lives, but by examining those we expect to live short ones.

The influence of smoking on longevity and mortality risk is well known, substantially lowering the former and raising the latter. That Jeanne Calment smoked for nearly her whole adult life makes her the most noteworthy of outliers. A recent study considered precisely this point, searching a population of smokers to find a set of genetic differences that distinguished the longest-lived. The authors' previous research had suggested that long-lived smokers were a biologically distinct group that would repay further study, and so it proved. When they took their findings and applied them to a "validation sample" of non-smokers they found the presence of these genetic markers resulted in "an over threefold increase in the likelihood of being a centenarian".

"[It] is likely that long-lived smokers possess variants which prevent genomic instability and allow them to survive to more extreme ages. Genomic instability also happens to be one of the hallmarks of cancer pathogenesis (36), thus the same genes that may promote survival among smokers may also be important for cancer prevention"

More work will undoubtedly follow here, but it is clear that searches for the genetic components of human longevity are bearing some fruit. While we're unlikely to ever test these findings against the indomitable lady herself, Jeanne Calment's secret may be closer to revelation than ever.

References

Gierman, H.J., Fortney, K., Roach, J.C., Coles, N.S., Li, H., Glusman, G., et al. (2014) Whole-Genome Sequencing of the World’s Oldest People PLoS ONE 9(11): e112430. doi:10.1371/journal.pone.0112430

Willcox, D. C., Willcox, B. J., Hsueh, W.-C., & Suzuki, M. (2006). Genetic determinants of exceptional human longevity: insights from the Okinawa Centenarian Study. Age, 28(4), 313–332. http://doi.org/10.1007/s11357-006-9020-x

Gross, L., The Key to Longevity? Having Long-Lived Parents Is a Good Start 10.1371/journal.pbio.0040119

Atzmon, G., Rincon, M., Schecter, C.B., Shuldiner, A., Lipton, R., Bergman, A. Barzilai, N. Lipoprotein Genotype and Conserved Pathway for Exceptional Longevity in Humans doi: 10.1371/journal.pbio.004011/p>

Levine, M. E. and Crimmons, E. M. (2015). A Genetic Network Associated With Stress Resistance, Longevity, and Cancer in Humans doi: 10.1093/gerona/glv141

Levine, M. E. and Crimmons, E. M. (2014). Not all smokers die young: a model for hidden heterogeneity within the human population doi: 10.1371/journal.pone.0087403

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