Sonntag, 13. November 2016

Large ongoing Primary Prevention Studies

In this article I want to highlight large studies that are being performed in relatively healthy populations, or which provide relevant data to further the goal of delaying aging and age-related diseases.

To provide a complete picture I looked into various reviews and the notes and ideas I already had. Keeping track of new nutraceutical and health related developments used to be a big pastime of mine so I hope the below list is somewhat complete. In addition to literature search, I queried a large clinical trials database using various terms. One variation was for example a query for "Interventional Studies | mortality | Adult | Phase 3, 4 | Studies with safety issue outcome measures" yielding 1107 hits. From this list, I selected studies with n > 1000 which yielded approx. 255 results, which were then hand search. In this way the clinicaltrials database helped me to identify a few studies I would have missed otherwise and what follows are short notes on interesting trials.

Dienstag, 1. November 2016

Coffeehouse notes on GH/IGF-1, CR and life span

Both Ames and growth hormone receptor knock-out (GHRKO) mice have disruptions in the GH pathway (11).

Surprisingly, however, studies suggest that GHRKO mice show more robust life span extension than Ames dwarfs. For one, the GHRKO model holds the absolute longevity record for lab mice. Secondly, it is much less responsive to caloric restriction (CR), while reducing calories extends the lifespan of Ames dwarfs quite robustly. Third, Ames dwarfs lack TSH, which might be beneficial, yet do not outlive GHRKOs (alternatively, this means TSH is only a minor player).

However, this notion in itself is controversial, because these mice have defects in the same pathway. In Ames dwarfs growth hormone (GH) is absent and GHRKO mice simply lack the GH receptor.

The hypothesis of the highly robust GHRKO mouse has two important implications worth exploring. On the one hand, it suggests that if CR fails to increase lifespan in this model it may work exclusively through GH signaling, which I don't believe. In addition, it would mean that the GHR receptor might have functions independent of GH binding and that the GHRKO mouse is meaningfully different from the Ames dwarf. When I talked to researchers at the last conference, some were quite convinced that there is a "magic ingredient" to the GHRKO mouse responsible for its robustness. Let's call it magic, because no one really knows what it is.

So it is reasonable to hypothesize that GHRKO, with the magic pathway fully suppressed, imposed on top of Ames dwarfism, magic pathway still partly active, would further improve life span and healthspan. Before we discuss the paper by Gesing et al. 2016 (1) testing this proposition, I want to give an introduction to GH in aging and briefly review key studies and controversies.