A political philosopher's reflections on politics, philosophy, science, medicine and law. "Enlightenment is man's emergence from his self-incurred immaturity" (Immanuel Kant, 1784).
posted by Colin Farrelly at 9:16 PM
posted by Colin Farrelly at 10:35 PM
The cellular basis of age-related behavioral decline remains obscure but alterations in synapses are likely candidates. Accordingly, the beneficial effects on neural function of caloric restriction and exercise, which are among the most effective anti-aging treatments known, might also be mediated by synapses. As a starting point in testing these ideas, we studied the skeletal neuromuscular junction (NMJ), a large, accessible peripheral synapse. Comparison of NMJs in young adult and aged mice revealed a variety of age-related structural alterations, including axonal swellings, sprouting, synaptic detachment, partial or complete withdrawal of axons from some postsynaptic sites, and fragmentation of the postsynaptic specialization. Alterations were significant by 18 mo of age and severe by 24 mo. A life-long calorie-restricted diet significantly decreased the incidence of pre- and postsynaptic abnormalities in 24-mo-old mice and attenuated age-related loss of motor neurons and turnover of muscle fibers. One month of exercise (wheel running) in 22-mo-old mice also reduced age-related synaptic changes but had no effect on motor neuron number or muscle fiber turnover. Time-lapse imaging in vivo revealed that exercise partially reversed synaptic alterations that had already occurred. These results demonstrate a critical effect of aging on synaptic structure and provide evidence that interventions capable of extending health span and lifespan can partially reverse these age-related synaptic changes.
....The connections between your nerves and muscle deteriorate with age--a phenomenon that may help explain the serious loss of muscle that often strikes old people. New evidence suggests that caloric restriction--a nutritionally complete but low-calorie diet--could help prevent these changes. According to a study published this week in the Proceedings of the National Academy of Sciences, a very-low-calorie diet, and to a lesser extent exercise, can prevent or slow some aspects of muscle decline in aging mice.
....The findings are among the first to show that caloric restriction has a robust effect on the nervous system, which has been a matter of debate. "This paper demonstrates the protective effect of dietary restriction on muscle and the neurons that regulate muscle function," says Mobbs. "It's one of the most convincing papers I have seen demonstrating a protective effect of dietary restriction in neural function."
Those who are disinclined to diet for their whole lives still have hope, however. Mice that exercised for a month in old age also had healthier neuromuscular junctions, though the findings weren't as significant as those for caloric restriction. "Just a month of exercise actually seemed to reverse the course of the downward spiral," says Lichtman.
"If there were ever two scientists who did not want to hear this result, it's us," says Lichtman, of himself and Sanes. "We don't love to exercise, and I find it real torture to starve myself." Because few people want to or are able to maintain a severely restricted diet, scientists and drug developers are searching for molecules that can mimic these health-boosting effects.
posted by Colin Farrelly at 12:54 PM
Newts and salamanders have brilliant personal-injury insurance: lose a tail or leg, and another grows in its place, good as new. Now, researchers in the United States say that they've found a way to recreate this ability in mice, opening the door to the possibility of regenerating damaged tissue in humans.
Compared with these lower vertebrates' ability to regrow missing limbs, humans and other mammals "are pretty pathetic", says Helen Blau, a regenerative biologist at Stanford University School of Medicine in Stanford, California, and the study's lead author1. "We can regenerate our livers, but not much else," she says.
So the burning question for researchers has been: what do these amphibians have that we lack?
....The researchers homed in on a tumour-suppressor gene called Arf that is present in mammals but not in regenerating vertebrates. Using a gene-silencing technique called RNA interference to temporarily knock down both Arf and Rb in cultured mouse muscle cells, they found that the treated cells re-entered the cell cycle and began proliferating.
When the genes' activities were restored, the cells returned to their differentiated state. Newly generated muscle cells transplanted into living mice were able to integrate into the animals' muscle tissue.
An outstanding biological question is why tissue regeneration in mammals is limited, whereas urodele amphibians and teleost fish regenerate major structures, largely by cell cycle reentry. Upon inactivation of Rb, proliferation of postmitotic urodele skeletal muscle is induced, whereas in mammalian muscle this mechanism does not exist. We postulated that a tumor suppressor present in mammals but absent in regenerative vertebrates, the Ink4a product ARF (alternative reading frame), is a regeneration suppressor. Concomitant inactivation of Arf and Rb led to mammalian muscle cell cycle reentry, loss of differentiation properties, and upregulation of cytokinetic machinery. Single postmitotic myocytes were isolated by laser micro-dissection-catapulting, and transient suppression of Arf and Rb yielded myoblast colonies that retained the ability to differentiate and fuse into myofibers upon transplantation in vivo. These results show that differentiation of mammalian cells is reversed by inactivation of Arf and Rb and support the hypothesis that Arf evolved at the expense of regeneration.
posted by Colin Farrelly at 7:42 AM
I am the Sir Edward Peacock Professor of Political Theory in the Department of Political Studies, Queen's University (Cross-appointed with Philosophy) in Canada.
