The Killer Chromosome

Y men die sooner

Yuri Deigin
3 min readMar 10, 2017

Think only human males live less than females? Think again! Take a look at 37 pages of data from the book Why Men Die Younger: Causes of Mortality Differences by Sex, especially check out Appendix F — there are over 100 species there:

Some might think that men live less than women because they are so much more reckless, spending their younger years engaging in all sorts of dangerous undertakings — riding motorcycles, binge drinking or playing contact sports. But that explanation, while plausible at first glance, is at best incomplete if not flat out wrong: the probability of death in men is higher than in women at any age, even in serene 60s and 70s.

The source of their demise lurks in the Y chromosome. No wonder castration extends life, in one experiment by 20% (13.6 years), and in Korean eunuchs by 30–40% (15–19 years).

But the most interesting observation is that male lifespan can be prolonged even without castration — by removing or silencing certain “deadly genes” on the Y chromosome itself. This is what Bulgarian (Tsoneva) and Soviet (Kuznetsova) scientists established in the 1980s, studying exceptionally long-living men:

“Descriptions of the relationship between large size C-blocks on Y chromosome and longevity in a Bulgarian population (Tsoneva et al., 1980) and the increased frequency of ‘very large’ C-blocks in human subjects aged over 80 years in the Edinburgh area (Buckton et al., 1976) were published previously.

A large-sized C segment on the Y chromosome and a long Y chromosome are typical both of the long-lived Ukrainian and Abkhasian males. Thus, we have established a definite association between the individual chromosomal polymorphism variants on the Y chromosome and the male longevity in different regions.”

Above, C-blocks or C-segments refer to heavily condensed, essentially silenced regions of the Y chromosome.

Even more intriguingly, in 1987 Kirby Smith discovered a group of 14 Amish men with Y-chromosomal deletions who lived about 20% longer than their peers (82 vs. 68–71 years):

Source: The Future of Aging: Pathways to Human Life Extension by Gregory M. Fahy, Michael D. West, L. Stephen Coles, Steven B. Harris

Many men wouldn’t trade their gonads for even a 50% life extension, so the great thing about the Amish was that they were fully functional men, with children and all, and still enjoyed a 20% life increase. So if we can figure out what genes were missing in their Y chromosomes and silence them in ours using CRISPR or gene therapy, we could have the best of both worlds.

Curiously, the Y-chromosome is very small: it carries only 71 coding genes. So it would be extremely interesting to pinpoint which particular areas were missing in these Amish men. In 1987 tools to do this did not exist, but today you can sequence your entire genome for $1000.

Sources:

  • Why Men Die Younger: Causes of Mortality Differences by Sex. Barbara Blatt Kalben
  • The Future of Aging: Pathways to Human Life Extension. Gregory M. Fahy, Michael D. West, L. Stephen Coles, Steven B. Harris

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Yuri Deigin

Longevity maximalist currently building rejuvenating gene therapies based on in vivo partial cellular reprogramming with Yamanaka factors.