Advances in the endocrinology of aging

A common thread that links seemingly disparate aspects of aging biology is that age-related change is not a cell-autonomous feature operating entirely in response to intrinsic factors within individual cells. Rather, cell-cell communication (via contact, paracrine, and endocrine signaling) is key.

For a quick review that puts a lot of recent data on this subject in one place, check out this recent piece by Francis Bellino (emphasis and formatting are mine):

The purpose of this brief review is to highlight some of the more important advances in endocrinology of aging research over the past year. …

First, exploration of the early steps in the generation of the internal steroidal hormonal signal involved in lifespan extension via the insulin/IGF-like signaling pathway in the nematode by two research groups revealed that the product of cholestanoic acid derivatives metabolized by a cytochrome P-450-like protein activates a protein with homology to the mammalian nuclear receptor superfamily, a process strikingly similar to the steroid hormone signaling pathway documented in mammalian systems.

Second is the discovery that sirtuins, proteins that regulate lifespan in model organisms, enhance pancreatic insulin secretion in mice following a glucose challenge, suggesting the potential to regulate mammalian lifespan through regulation of the insulin signaling pathway.

Third, the newly discovered hormone klotho, which also plays a role in regulating lifespan, in this case in mice, is reported to not only negatively affect insulin sensitivity but, perhaps more importantly, significantly affects calcium and phosphate metabolism as a required cofactor of Fgf-23 signaling.

Finally the gonadotropin FSH is shown to directly affect bone density in mice separate from any direct effect of estrogen, suggesting that reproductive hormones other than estrogen can directly impact menopause-associated pathophysiology in non-reproductive tissues.

The idea that much of aging is regulated endocrinologically, with hormone-producing cells acting “at a distance”, may be heartening for those who might hope to intervene in the process. It would, after all, be a much easier matter to add soluble factors to the blood (or even deplete specific ones, given very reasonably-sized advances in immune-based therapies) than to make an internal adjustment to every cell in the body.