Thymus Transplant Extends Life in Old Mice

Amidst the preprint list of the Rejuvenation Research journal, I see an interesting paper I'd somehow missed: life span can be extended in old mice by transplant of a young thymus.

Noninvasive Neonatal Thymus Graft into the Axillary Cavity Extends the Lifespan of Old Mice:

Neonatal thymus grafts exert a rejuvenating action on various immunological and nonimmunological functions found altered in old mice. Commonly, half of a thymus is grafted under the kidney capsule. The invasiveness of the surgical procedure and the use of limited thymus tissue may explain why precedent survival kinetics remain unaffected.

In this trial, we grafted two neonatal thymi into the axillary cavity of old mice, thus reducing the invasiveness of the intervention and increasing the amount of grafted neonatal tissue. Using a Piantanelli parametric model of survivorship, we found a significant change in mortality rate between the two groups (thymus graft and controls).

You might recall that the degeneration of the thymus over time - a process known as involution - is one of the limits placed upon your immune system. The thymus is the source of T cells, the workers of the active immune system. Considered within the framework of a normal life span, the thymus spins up early, churns out your population of T cells while you are a child, and then largely shuts down once you reach adulthood. You are left with what is essentially a fixed population of immune cells to see you through the rest of your life. Which is a simplification of a more complex set of processes, but close enough for our purposes here.

The degenerating effectiveness of an aging immune system results in large part from the limited T cell population: it runs out of T cells that are not already assigned to specific tasks. Over the years, exposure to persistent but usually harmless viruses like cytomegalovirus (CMV) chews up your quota of T cells, leaving too few to effectively defend against new threats, destroy senescent cells, or destroy cancerous cells before they can form a tumor. So you suffer, and the degenerations of aging are accelerated.

One possible way to deal with this problem and restore the immune system to a more youthful capacity is to destroy the clutter. Use targeted therapies of the type under development by cancer researchers to kill off the T cells that are dedicated to fight CMV, and then repopulate your immune system via stem cell medicine. Or, more radically, completely destroy and then recreate your immune system, wiping the slate clean. This second method has already been achieved in early trials for autoimmune diseases.

But another approach is to simply boost the number of immune cells circulating in the body. I've discussed rejuvenation of the thymus through tissue engineering or other techniques in the past - essentially gearing it up to generate more T cells than would normally be the case. Transplantation of young thymus tissue, as the researchers in the paper quoted above have demonstrated, is one way of validating this approach. The immune system is so critical to resisting various forms of progressive cellular and other biochemical damage in the body that it is not unreasonable to expect at least some enhanced longevity to result from its restoration.

ResearchBlogging.orgBasso, A., Malavolta, M., Piacenza, F., Santarelli, L., Marcellini, F., Papa, R., & Mocchegiani, E. (2009). Noninvasive Neonatal Thymus Graft into the Axillary Cavity Extends the Lifespan of Old Mice Rejuvenation Research DOI: 10.1089/rej.2009.0936


Seems like regeneration of existing organs by way of stem cells, thymus, heart, liver,...,etc.
have the problem of shotening the teleomeres. So, it would seem one is replacing a defective unit with an older organ minus the defect.
Just a thought.

Posted by: Frank J. Ujlaki at March 15th, 2010 9:06 AM

What's the effect size? 10% longer lifespan? 100%? 1%?

Posted by: dlr at August 31st, 2013 5:29 PM

I think we should not forget that thymus secret hormones that can be influence on Aging

Posted by: jacob at October 22nd, 2015 6:13 AM

Frank J. Ujlaki, you asked a good question at the time. It's five years later, and we now understand that telomeres can be made to grow longer via a number of mechanisms.

Posted by: Donovan Walker at December 7th, 2015 9:42 PM
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