Three links in Aging, Regenerative Medicine & Healthy Lifespan Extension: 17 December 2013

1. DNA methylation age of human tissues and cell types by Steve Horvath: This is the type of relevant data mining study most bioinformaticians are dreaming of: you pull together a large body of publicly available datasets (CpG methylation) that are not too heterogeneous (Infinium type II assay on Illumina 27K or Illumina 450K array platform), derive robust statistical results (develop a multi-tissue predictor of age) and apply it on a medically relevant field (20 cancer types exhibit significant age acceleration, with an average of 36 years).

DNAm age is arguably a promising marker for studying human development, aging, and cancer. It may become a useful surrogate marker for evaluating rejuvenation therapies. The most salient feature of DNAm age is its applicability to a broad spectrum of tissues and cell types. Since it allows one to contrast the ages of different tissues from the same subject, it can be used to identify tissues that show evidence of accelerated age due to disease (for example, cancer). It remains to be seen whether the DNAm age of easily accessible fluids/tissues (for example, saliva, buccal cells, blood, skin) can serve as a surrogate marker for inaccessible tissues (for example, brain, kidney, liver).

Future research will need to clarify whether DNAm age is only a marker of aging or relates to an effector of aging. In conclusion, the epigenetic clock described here is likely to become a valuable addition to the telomere clock.

2.  Use your noggin, dickkopf! Can stem cells really regenerate the human heart? Lessons from developmental biology by Paula Sommer.

Several experimental options to induce regeneration of the damaged heart tissue are available: activate the endogenous cardiomyocytes to divide, coax the endogenous population of stem cells to divide and differentiate, or add exogenous cell-based therapy to replace the lost cardiac tissue…

It is believed that stem cells secrete various growth factors, cytokines and signalling molecules that stimulate the endogenous stem cells or cardiomyocytes to proliferate. The inability of the exogenously administered stem cells to contribute directly may be due to their lack of potency. It is therefore thought that, to regenerate substantial cardiac tissue, either synthetically generated stem cells such as iPS or directly re-programmed somatic cells (generated without the use of viral vectors) are a more feasible, though expensive, option.

The development of a ‘cell-free’ treatment with the administration of molecules that either stimulate the endogenous cardiomyocytes, or stem cells to divide, or molecules that create a permissive environment to stimulate regeneration would be an ideal solution, eliminating the need for surgery.

3. Hal Barron on Google’s Calico: finally the ‘mandatory’ Calico link from hire #1 or #2 with some newish informative hints. One way to determine better the rate of aging is to use something like the epigenetic clock mentioned in link #1 above.

On the scientific front, he said, Calico will know more about fundamental biological processes in the next five years or less by aggregating data in a way that medical geneticists are not able to do today and overlaying that with research like that from Calico teammate Cynthia Kenyon.

Driving that progress, Barron said, will be the quest to find a better way to determine the rate of aging than simply looking at someone’s face and saying that they “age well.”