Back in full flow for 2009, you'll find a brace of posts on aging research from the past few days over at Ouroboros.
it should come as no surprise to learn that chronic psychological stress has been associated with accelerated telomere shortening in circulating white blood cells. The problem arises in trying to provide a biological mechanism that links this form of stress to increased telomere loss.
I’m sitting in an auditorium listening to a seminar by Laura Niedernhoefer from U. Pittsburgh. She’s telling us that Ercc1-/- mice, which are deficient in nucleotide excision repair, show transcriptional changes that mirror those found in old wildtype or unusually long-lived mutant animals. Her data is strongly reminiscent of recent findings that progeroid DNA repair mutants exhibit transcriptional similarities to aging calorie-restricted and dwarf animals.
Because senescent cells accumulate with age, senescence has been considered a biomarker of aging - that is to say, a measurable feature of a tissue that would allow us to calculate its "biological" or "physiological" age without necessarily knowing the chronological age of the donor. This makes abundant sense: tissues with more senescent cells would have lower proliferative capacity and higher levels of deleterious secreted factors; given two samples of the same chronological age, one could argue that the one containing more senescent cells was "older" in some meaningful way. This idea is central to a recent paper demonstrating that senescence correlates negatively with the efficacy of a transplanted tissue.
Another group, working in a mouse model, has shown that older donor tissues express higher levels of the senescence marker p16, which is negatively correlated with proliferative capacity. But the old material doesn’t just start from behind, but also gets worse more rapidly: p16 levels rise dramatically in old grafts following transplantation, much faster than in young grafts, indicating that older cells are more sensitive to the stresses of undergoing transplantation and that they respond to this stress by undergoing senescence.
What causes organ failure during aging? Is it stochastic, with individual organ systems deteriorating and failing more or less independently - or is it more like a chain of dominoes, with a primary organ failure in one tissue putting pressure on other tissues and accelerating their decline?
The most surprising result is that [mutants lacking uncoupling protein] have shorter lives, implying that mitochondrial uncoupling is a key mechanism for controlling oxidative stress throughout the lifespan.