A giant step for mankind that started with a mouse!

This past week dropped several major releases in the anti aging research field, and one of them, a study from Maria Blasco’s group, is large enough that I want to walk through it deliberately. But first, a brief note on how fast this field is moving.

A year ago I had the chance to stand in front of an interested audience at David Wolfe’s Longevity Now Conference and teach about omega 3, telomeres, epigenetics, and several adjacent topics. At the time, those terms barely registered with the general public. Today, those same topics are getting front page coverage, and Suzanne Somers’ latest book Bombshell devotes 21 pages to telomeres, telomerase, and TA-65, topics we spent an entire book on in 2010. The field is breaking through.

The Blasco gene therapy study

The headline study is Bernardes de Jesus et al., 2012, from Maria Blasco’s lab at CNIO in Madrid, published in EMBO Molecular Medicine. The setup matters, so let me describe it carefully.

Researchers used an adeno associated virus, AAV9, as a vector to deliver the gene for telomerase reverse transcriptase, TERT, into mice. The TERT gene is the catalytic component of telomerase, the enzyme that maintains the protective caps on the ends of chromosomes. AAV9 was chosen because, unlike earlier viral vectors used in similar experiments, it does not integrate randomly into the host genome and does not carry the cancer risk that has dogged gene therapy attempts in the past.

The mice were dosed once. One injection, not a course of treatment. The team then tracked them for the rest of their lives.

The results

Adult mice treated at one year of age, the rough mouse equivalent of middle age in a human, lived roughly 24 percent longer than untreated controls. Old mice treated at two years of age, late life in mouse terms, lived roughly 14 percent longer than untreated controls.

And critically, the treated mice did not develop more cancer than the controls. This is the part that should silence the long running objection that telomerase activation must cause cancer. The Blasco team showed that under controlled conditions, with a properly targeted vector, telomerase therapy extends mouse lifespan without elevating cancer incidence. Other groups, including Ron DePinho’s lab, have shown similar reversal of aging biomarkers in telomerase deficient mouse models.

What this does and does not mean

Two predictable objections to this work need to be addressed before they show up in the comments.

First, the mice were not made immortal. Of course they were not. Mice do not age purely through telomere attrition. By most estimates, telomere related mechanisms account for roughly half of mouse aging, with mitochondrial decline, immune senescence, and various tissue specific failures filling out the rest. A pure telomerase intervention is not expected to make a mouse immortal. The fact that it adds 14 to 24 percent of life with no cancer increase, from a single injection in already aged animals, is the impressive part.

This also suggests that in humans, where telomere biology may explain a larger share of total aging than it does in mice, the eventual effects of a clinically viable telomerase intervention could be larger than the mouse numbers imply. Could be. Not is. The translation from mouse biology to human biology is never clean.

Second objection. Mice are not people. Correct. But Blasco’s same lab has published work establishing that mice are a valid model for the telomere component of human aging, which is the specific question this study is addressing. The mouse to human bridge in telomere biology is more solid than in many other areas of aging research.

Where this leaves us today

The economic and regulatory incentives to develop a viral gene therapy for human aging are essentially nonexistent at the moment. Pharmaceutical companies do not have a disease code for aging, and the FDA does not yet treat aging as an indication. That will probably change in the next decade, but not tomorrow.

For now, the only practical telomerase activating intervention with human safety and efficacy data is TA-65, the small molecule activator derived from astragalus that Blasco has also studied in mice. Blasco’s mouse work with TA-65 showed measurable lifespan and healthspan benefits with no increase in cancer. The human data, while smaller in scale, are consistent with the animal work on the safety side and have shown improvements in immune markers and short telomere length in supplemented populations.

What this means in plain terms

Two years ago, when our book The Immortality Edge came out, the criticism was that it was speculative. The criticism has not aged well. Every major prediction in the book about where telomere science would go has either been confirmed or has work actively moving in that direction. The gene therapy work is one of several confirmations.

I cannot tell you to wait for the human gene therapy version. None of us has that kind of time. But the direction is now clearly established, and the practical interventions available today, including TA-65 for those who want to invest in it, supportive lifestyle factors, and good supplementation, are positioned within a framework that is no longer speculative.

The field has shifted from is this even real to how do we deploy it safely. That is a different conversation, and it is the one worth having.

— Doc