Regeneration


Welcome to the first installation of Hourglass, a blog carnival devoted to the biology of aging. This first issue corresponds with the second blogiversary of Ouroboros, but mostly I consider it a celebration of the excellent (and growing) community of bloggers who are writing about biogerontology, lifespan extension technologies, and aging in general.

Without further ado, then, let’s get started:

Reason at Fight Aging! reports on AnAge, a curated database of longevity, aging, and life history in a wide range of animals. The database contains information about average and maximum longevity within species, and also cool features like lists of the “world-record” holders for the longest-lived organisms on the planet. AnAge will be a great tool for anyone interested in studying evolution of negligible senescence or exploiting lifespan diversity across related species to learn about mechanisms of aging. For those who are interested in databases of this kind, AnAge is a component of a larger project, the Human Ageing Genomic Resources.

The most widely studied technique for extending the lifespan of diverse animals is calorie restriction (CR), whose benefits in humans are still under careful study. One of the disadvantages of studying humans, of course, is that you can’t keep them in completely controlled environments, free from temptation to cheat on their defined diets — but this may be more than adequately compensated by the main advantage of human subjects, namely, that they can tell you how they’re feeling about the study while it’s underway. Over at Weekly Adventures of a Girl on a Diet, Elizabeth Ewen describes her experiences as a subject in the CALERIE study, a large-scale test of the effects of CR on humans (we’ve discussed CALERIE here before). In her post, Elizabeth describes the CALERIE study in detail, and also critically assesses some of its specific features — something that no mouse, however talented, could ever do.

While methods like CR may delay aging, or at least aspects thereof, they can’t stop it dead in its tracks — and they certainly can’t reverse large-scale age-related decline in tissue function. For those applications, we will have to look to more dramatic interventions, such as tissue engineering. In this exciting new field, biomedical engineers are seeking, essentially, to grow new organs for people whose originals have worn out due to injury, disease, or aging itself. One of the major challenges of tissue engineering is morphology: Even assuming that the appropriate sorts of stem cells are available, and that one can induce them to differentiate appropriately, how would one guarantee that they grow into the appropriate spatial architecture for efficient function? According to Attila Csordás at Partial Immortalization, one solution would be to use the “decellularized matrix hack“: to chemically or enzymatically remove the cells from cadaver organs, and then regrow new cells over the extracellular matrix left behind. (Since ECM is much more highly conserved than cell-surface markers, I suspect that such an approach could also be used to overcome immune rejection issues.) Attila’s post includes a video of the application of this concept to the heart.

Moving from the heart to the brain, we’re going to finish up with two huge posts about aging, mental fitness, and age-related changes in neurological function.

Ward Plunet at BrainHealthHacks writes about recent evidence that smarter people live longer. This is true whether your metric of intelligence is education (which could be problematic, as education levels are often correlated with lifelong affluence and access to medical care) or whether you’re looking at individual genetic variations correlated with both longevity and intelligence. It’s a giant post that quotes several articles from the primary literature as well as studies by international organizations. Nature, nurture, Ward has it all.

Assuming for the moment that long life and intelligence are associated — in which direction does the causal arrow point? We’re still unsure about that at the level of the whole organism, but in the case of brain health we know a bit more. At SharpBrains, Alvaro Fernandez interviews U. of Illinois’ Prof. Art Kramer, who describes ways that everyone can extend their mental healthspans and even delay the onset of age-related neurological dysfunction such as Alzheimer’s disease. That’s just the beginning of the lengthy interview, which goes on to talk about people’s desire for magical solutions to age-related declines in mental function, the results of prior studies, and the synergy between physical and cognitive exercise — among many other subjects.

Thanks for reading. I’m going to try to make Hourglass a monthly carnival on the second Tuesday of every month, so the next one will be held on August 12th. If you’re interested in hosting, please email me.

The ability of salamanders to regenerate lost limbs has long fascinated biologists, and the prospect of stimulating such dramatic healing in humans attracts the attention of the translational research / regenerative medicine folks. A new study by Kumar et al. reveals a dramatic role for a factor not previously implicated in regeneration or wound healing:

The anterior gradient protein family member nAG is a secreted ligand for Prod 1 and a growth factor for cultured newt blastemal cells. nAG is sequentially expressed after amputation in the regenerating nerve and the wound epidermis-the key tissues of the stem cell niche-and its expression in both locations is abrogated by denervation. The local expression of nAG after electroporation is sufficient to rescue a denervated blastema and regenerate the distal structures. Our analysis brings together the positional identity of the blastema and the classical nerve dependence of limb regeneration.

This study is exciting for several reasons. Not only is nAG both necessary and sufficient to stimulate regeneration, but it is also a soluble factor. This makes it easier to envision a role for similar soluble factors in future medical regenerative applications. nAG isn’t a magical cure-all protein, but rather a very important factor secreted at a specific time during regeneration by the neural fibers as they regrow. The authors elegantly demonstrate that by adding nAG in the absence of re-innervation, somatic limb regeneration does occur, but without new nerve formation (as well as being deficient in skeletal muscle re-formation).

A human homolog of nAG has been identified, but has yet to be characterized.

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