Immortality – Reversing Aging

There is news today about some Harvard scientists who have successfully rejuvenated worn out organs in elderly mice. In fact, the claim in the press reads … “turned weak and feeble old mice into healthy animals by regenerating their aged bodies.”.

Now this sounds fascinating, but is it really true? A ton of questions fall out from all this such as, does this imply that we are just about to all live a lot longer? If they truly have done this in mice, can the same be applied to humans? Would we actually live longer, or would we simply retain better health in old age?

The claim being made is indeed truly amazing, it does appear to be a promise of eternal youth …

“What we saw in these animals was not a slowing down or stabilisation of the ageing process. We saw a dramatic reversal – and that was unexpected,“

OK, lets skip the press and go directly to the study itself. The article was received 8 May by Nature (so its not new). What has happened is that it has been through peer review and was published yesterday (28th Nov). The title is “Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice”, and the abstract reads … (you might like to skip this next bit) …

An ageing world population has fuelled interest in regenerative remedies that may stem declining organ function and maintain fitness. Unanswered is whether elimination of intrinsic instigators driving age-associated degeneration can reverse, as opposed to simply arrest, various afflictions of the aged. Such instigators include progressively damaged genomes. Telomerase-deficient mice have served as a model system to study the adverse cellular and organismal consequences of wide-spread endogenous DNA damage signalling activation in vivo1. Telomere loss and uncapping provokes progressive tissue atrophy, stem cell depletion, organ system failure and impaired tissue injury responses1. Here, we sought to determine whether entrenched multi-system degeneration in adult mice with severe telomere dysfunction can be halted or possibly reversed by reactivation of endogenous telomerase activity. To this end, we engineered a knock-in allele encoding a 4-hydroxytamoxifen (4-OHT)-inducible telomerase reverse transcriptase-oestrogen receptor (TERT-ER) under transcriptional control of the endogenous TERT promoter. Homozygous TERT-ER mice have short dysfunctional telomeres and sustain increased DNA damage signalling and classical degenerative phenotypes upon successive generational matings and advancing age. Telomerase reactivation in such late generation TERT-ER mice extends telomeres, reduces DNA damage signalling and associated cellular checkpoint responses, allows resumption of proliferation in quiescent cultures, and eliminates degenerative phenotypes across multiple organs including testes, spleens and intestines. Notably, somatic telomerase reactivation reversed neurodegeneration with restoration of proliferating Sox2+ neural progenitors, Dcx+ newborn neurons, and Olig2+ oligodendrocyte populations. Consistent with the integral role of subventricular zone neural progenitors in generation and maintenance of olfactory bulb interneurons2, this wave of telomerase-dependent neurogenesis resulted in alleviation of hyposmia and recovery of innate olfactory avoidance responses. Accumulating evidence implicating telomere damage as a driver of age-associated organ decline and disease risk1, 3 and the marked reversal of systemic degenerative phenotypes in adult mice observed here support the development of regenerative strategies designed to restore telomere integrity.

OK, I did warn you that you might prefer to skip that last bit. Lets simplify it a bit.

• This is all about telomere shortening
• Cells in your body contain 23 pairs of chromosomes
• At the ends of each chromosome is a protective cap called a telomere
• Each time a cell divides, the telomeres are snipped shorter, until eventually they stop working

They believe that its this that causes ageing … still with me? … good, then lets keep going …

• They bred mice that lacked an enzyme called telomerase that stops telomeres getting shorter … net effect the mice aged prematurely
• Then they gave the mice injections to reactivate the enzyme … and … it repaired the damaged tissues and … much to their surprise …. reversed the signs of aging.

So, can we do this in humans? Are you willing to volunteer to try it out? .. remember now, it promises to potentially restore your youth ….

Now before you answer that consider this, mice make telomerase throughout their lives, but humans are different. We live a lot longer, so the enzyme is switched off in adult humans. If this did not happen then cells would grow out of control and turn into cancer, so if they start giving you this enzyme, it might indeed help restore a bit of vigor, but your risk of cancer would leap …

Now that you know that, are you still willing to sign up? Ah yes, nothing like knowing the details to help defeat the hype. Its still a fascinating discovery, but its not a fountain of youth, just an interesting small step. Tom Kirkwood, director of the Institute for Ageing and Health at Newcastle University, is quoted as saying:

“The key question is what might this mean for human therapies against age-related diseases? While there is some evidence that telomere erosion contributes to age-associated human pathology, it is surely not the only, or even dominant, cause, as it appears to be in mice engineered to lack telomerase. Furthermore, there is the ever-present anxiety that telomerase reactivation is a hallmark of most human cancers.”

So when faced with claims of “aging cures” .. be skeptical … its a extraordinary claim, so you should demand extraordinary proof.

The article in Nature can be found here.