Of the Aging Body, What Might Be Easiest To Rejuvenate?

There seems to be a case for believing that a number of the body's systems and cell types become less effective with age due to biochemical cues rather than any inherent deficiency of function. You might recall the ongoing debate over age-related decline in stem cells that maintain and repair muscle; back in 2005 a group demonstrated a rejuvenation of stem cell capacity by introducing young blood - i.e. replacing an "old" surrounding cellular environment with a "young" one, and all its attendent biochemical signals.

Recently, another group showed the mechanism by which capacity declines in neural stems cells with aging: they slow down, divide less often - but are still present in numbers. That might just be what aging muscle stem cells do also. Would a young environment wake up the neural stem cells also? What is it, exactly, about that environment that sets stem cells back to work?

While perusing PubMed, I came across another few recent examples of researchers investigating aging systems in the body that might be rejuvenated through changes in signaling. Stem cells feature prominently, even when discussing the rejuvenation of an aging immune system.

The molecular basis of ageing in stem cells

Here, we argue that cellular ageing is a reversible process, and this is determined by the balance of biological molecules which directly or indirectly control telomere length and telomerase activity, either through altering gene expression and/or modulating the epigenetic state of the chromatin.

Complexity of anti-immunosenescence strategies in humans

Immunosenescence is characterized by three main aspects: (i) the shrinkage of the T cell repertoire and the accumulation of oligoclonal expansions (megaclones) of memory/effector cells directed toward ubiquitary infectious agents; (ii) the involution of the thymus and the exhaustion of naive T cells; and (iii) a chronic inflammatory status called inflamm-aging. We present here possible strategies to counteract these main aspects of immunosenescence in humans ... the complexity of a rejuvenation approach is stressed, with particular attention to the inhibitory role played by the "old microenvironment" on the performance of progenitor cells, the best candidate to counteract the decline in regenerative potential characteristic of organs and tissues from old organisms.

Thymic rejuvenation and the induction of tolerance by adult thymic grafts

We report here that aged, involuted thymus transplanted as a vascularized graft into juvenile recipients leads to rejuvenation of both thymic structure and function, suggesting that factors extrinsic to the thymus are capable of restoring juvenile thymic function to aged recipients. ... These findings indicate that it may be possible to manipulate thymic function in adults to induce transplantation tolerance after the age of thymic involution.

Involution of the thymus is a whole interesting topic in and of itself - the body is a changing system from the moment the first cell divides.

A question still high on the list is "why are these systems turning themselves off with increasing age?" It's quite possible that this is because a dangerous fraction of the component cells are, in fact, damaged goods in later life. In the case of stem cells, for example, turning them all back on at full blast might just mean an orgy of cancer, due to a high level of random genetic damage accumulated over a lifetime.

As the second paper above points out, "easy" is a relative term. But we should be encouraged that researchers are thinking along the right lines - given an aging biological system that leads to frailty and suffering, what can we do to restore it to full functionality? That is a path towards longer, healthier lives, freed from the slow and inevitable breakdown of form and function that only exists because we are not yet capable enough to enact repairs.

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This is a natural experiment on the efficacy of public vs. private R&D.

Many scientists in the private sector are working on rejuvenating hair follicles because of the huge commercial possibilities attending to that project.

In stark contrast, obviously, scientists who work on government grants can't focus on fighting baldness when there's a War on Cancer to be won.

A pill or therapy that cured baldness would be a blockbuster drug on the order of Viagra. The profit motive is huge.

Meanwhile, altruism dictates that no one should work on the hair loss problem when their abilities might be better put to use looking for cures to crippling or life threatening diseases.

It'll be interesting to see which runner gets to their finish line faster.

Posted by: c at December 22nd, 2006 4:06 PM

The for-profit cancer research industry dwarfs the for-profit baldness research industry. There is far more money to be made in treating cancer, despite the higher regulatory burdens. Now imagine a world in which those regulatory burdens didn't exist. Government is a bulk package - you get research dollars, spent inefficiently, but you also get the suppression of far greater pools of research funding. A huge net loss.

Posted by: Reason at December 22nd, 2006 4:33 PM

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