IGF-1, FOXO and Telomeres at Ouroboros

Chris Patil at Ouroboros has dropped two sets of recent research into our laps for consideration, with a focus on continuing efforts to understand the intricacies of human biochemistry as it relates to longevity and aging.

I find most of the work on insulin metabolism and insulin-like growth factor-1 (IGF-1) somewhat heavy going. It's very much down in the depths of metabolic mechanisms, for all that it's related to straightforward demonstrations of single gene longevity mutations in lower animals. It's somewhat analogous to work on calorie restriction mechanisms - in that it draws together energy from food and longevity to a mysterious biochemical middle - but perhaps more opaque because practical applications aren't as advanced at this stage.

Telomeres are more intuitive, however:

Telomeres - the structures at the end of chromosomes - have a long history in biogerontology. Telomeres shorten with every cell division, essentially providing a 'clock' that ticks down until reaching some critical length, at which point the cell will undergo the permanent growth arrest known as senescence. Even though this clock is an important tumor suppression checkpoint (because it prevents cells that have divided many times from continuing to proliferate), senescent cells themselves contribute both directly and indirectly to aging (by diminishing regenerative capacity and secreting deleterious signaling molecules, respectively). Telomere length is also a useful biomarker: it is positively correlated with life expectancy, and appears to respond to environmental influences including chronic infection and psychological stress.

One item of note in the list is that telomerase appears to have other roles beyond lengthening telomeres:

recent studies have led some investigators to suggest novel biochemical properties of telomerase in several essential cell signaling pathways without apparent involvement of its well established function in telomere maintenance. … This review will provide an update on the extracurricular activities of telomerase in apoptosis, DNA repair, stem cell function, and in the regulation of gene expression.

This is important for those groups working on telomerase-based therapies, and has implications for the viability of the proposed WILT strategy that would disable telomerase in order to eliminate cancer. As always, it's a challenge to interfere precisely in human biochemistry when every component has multiple important functions.

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