Singing the Telomere Tune Part 2

I wanted to step off the soap box for Part 2 and walk through some new telomere science worth your time.

My friend Maria Blasco in Madrid just released an interesting study. I have teased Maria over the years about making a Methuselah mouse that lives 1,000 years while people are still dying at 80. The teasing aside, her mouse work is among the most important data we have on telomeres, aging, healthspan, and lifespan. The latest paper involves what she calls chimeric mice.

Using stem cells with very long telomeres and mixing them with normal cells at the earliest point of development, Maria’s group built mice that were a mosaic of long-telomere and average-telomere cells. They were able to track both populations over time using cell markers.

Why does this matter? When I write about telomeres in the popular press I am, in the eyes of the academic field, a nobody. When Maria writes, the field listens. Every clean study she puts out is one more brick in the structural case for telomeres as a real modifier of aging.

What she found

• The chimeric mice were healthy. No increase in cancer. This matters because the field still routinely uses the words cancer and telomerase in the same sentence as if one caused the other. In these mice telomerase was not increased. The telomeres were simply longer to start with. Longer telomeres did not produce cancer.
• Wound healing was faster in the chimeric mice than in the non chimeric controls.
• The cells with the longer telomeres accumulated less DNA damage with age. DNA damage builds up as cells divide. Above a threshold it either drives aging or, if the shut off mechanisms fail, drives cancer.
• Here is the catch. The chimeric mice did not live longer. Critics of the telomere theory will jump on this and stop reading. They should not. Senescence is driven by the accumulation of the shortest telomeres, not by the average telomere length. Half the cells having long telomeres does not save you if the other half are accumulating damage and pushing the body forward into senescence.

What that tells us

It is too early to call this a full hypothesis, but the working guess is this. Having some longer telomeres probably improves healthspan even if it does not extend lifespan. To get a lifespan effect you likely need most cells, not half, with longer telomeres. The earlier Blasco AAV9 telomerase experiments, where telomerase was turned on in most cells, did show increased lifespan and healthspan. That fits.

It also means Liz Parrish’s path of using AAV vectors to deliver telomerase is probably the right shape, even if it is years away from the clinic.

And my own roughly 1,200 base pair increase in measured leukocyte telomere length, over four plus years on TA-65, is not nothing either.

What to do tomorrow morning

Telomeres are not the only lever for aging, but the case for them as one lever is getting harder to dismiss. If you want to act on this in 2017, the practical pieces are still the same. Keep inflammation low. Keep your omega 3 status where it belongs. Get your sleep. If you choose to use a telomerase activator, use one with published human data, not a lab petri dish marketing claim.

Keep singing the telomere tune.

Dr Dave