Dienstag, 18. November 2014

Short notes: massively parallel in vivo screening; thoughts on senescence and telomeres

Recently, I attended two very useful seminars/talks. There are two kinds of talks. Those seminars that are helpful, but boring. And those that leave you amazed at every step. The boring ones can be useful when they give your mind time to wander, and ponder some minor detail of the talk, or think about your own research. These talks had a little of both worlds:

1. FunSel: Functional in vivo selection using adeno associated viruses [AAV].
AAV lead to efficient infection of post-mitotic tissues. Selection is based on a simple principle: if AAVs express protective proteins, they will be enriched in surviving cells. The main assumption is that there is some selection on the cell level, e.g. some cells die, others survive. If this works, you could imagine applying it to most diseases e.g. neurodegeneration, beta-cell death, muscle cell loss (sarcopenia), etc.
I am still searching for publications on this topic, as it appears that most of the research is still ongoing.

How could we adapt this technique to aging research if it works as promised? For example:
A. Using FunSel with a model of mitochondrial aging (the interested reader can figure out which one I mean)
B. More speculative: Using it for in vivo optimization of amino acid sequence and function, e.g. vector optimization

Montag, 3. November 2014

Age-related calcification: how prevalent is it in the animal kingdom?

It has been some time since I read about calcification. I can't access the below paper, but I find it fascinating just how prevalent this phenomenon seems to be across different species. Unfortunately, the wording of the abstract does not distinguish between idiopathic and age-related calcification. Perhaps I missed these papers, but I don't think age-related calcification has been studied (and shown to occur) in all these species. In fact, judging by the references most refer to the idiopathic type, but I have no time to read it in more depth. Edit: A brief e-mail exchange with the authors more or less confirmed my suspicion, their secondary/tertiary sources mostly deal with "regular" pathologic calcification.

Comp Med. 2014 Jun;64(3):224-9.
Extensive vascular mineralization in the brain of a chimpanzee (Pan troglodytes).
Connor-Stroud et al.

Spontaneous vascular mineralization (deposition of iron or calcium salts) has been observed in marble brain syndrome, mineralizing microangiopathy, hypothyroidism, Fahr syndrome, Sturge-Weber syndrome, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, and calciphylaxis in humans and as an aging or idiopathic lesion in the brains of horses, cats, nonhuman primates, mice, rats, cattle, white-tailed deer, and dogs. Here we present a 27-y-old, adult male chimpanzee (Pan troglodytes) with spontaneous, extensive vascular mineralization localized solely to the brain. The chimpanzee exhibited tremors and weakness of the limbs, which progressed to paralysis before euthanasia. Magnetic resonance brain imaging in 2002 and 2010 (immediately before euthanasia) revealed multiple hypointense foci, suggestive of iron- and calcium-rich deposits. At necropsy, the brain parenchyma had occasional petechial hemorrhage, and microscopically, the cerebral, cerebellar and brain stem, gray and white matter had moderate to severe mural aggregates of a granular, basophilic material (mineral) in the blood vessels. In addition, these regions often had moderate to severe medial to transmural deposition of mature collagen in the blood vessels. We ruled out common causes of brain mineralization in humans and animals, but an etiology for the mineralization could not be determined. To our knowledge, mineralization in brain has been reported only once to occur in a chimpanzee, but its chronicity in our case makes it particularly interesting.