On Anti-Aging

from reference 2


Throughout your life, your cells are continually replaced. The replacements are newly differentiated stem cells: cells which have somehow come to a decision regarding their fate in your body, and have thus undergone a transformation from a ready-to-become-something state, to a liver cell, a retinal cell, a skin cell, a brain cell (neuron). This further means that your stem cells (and others) are constantly dividing, a process called mitosis. The most fundamental operation in mitotic division is the replication (copying) of DNA. This is a multifaceted operation involving a large cast of molecular players including (amongst others) enzymes, cofactors, and nucleic acid building blocks.

When DNA is replicated, complementary nucleic acid bases are added one by one to each strand of the double helix as it is unwound, resulting in two copies of the original piece of DNA (chromosome). However, this presents a slight problem. The enzyme complex responsible for adding these base pairs (the process is called elongation) requires a bit of RNA at the end of the strand to get started. The solution is that part of the end of the DNA strand is snipped off and replaced with a chunk of RNA as a jumping off point. This would be an issue if these enzymes were chopping off pieces of "important" (functional) DNA; cells have so called "proofreading" mechanisms to look for the kinds of erroneous DNA sequences that would result from trimming parts off the end, which if found in large enough numbers, result in cellular suicide (apoptosis). Instead, and rather ingeniously, there are long sequences that cap the ends of the important parts of DNA called telomeres. The only function of these sequences is to be snipped apart, slowly ground down over time, by replication so that the important stuff in the middle doesn't get messed with in this process.

Telomeric DNA has been seen as a potential target for anti-aging therapy. The idea is simple: make telomeres longer, the animal lives longer because the animal's cells can replicate forever without ever being forced to snip "important" DNA during the replication part and ultimately apoptose. Furthermore, there is an enzyme whose job it is to lengthen telomeric DNA called, unsurprisingly, telomerase. Indeed, it is known that increased telomerase activity extends the lifespan of most human cell types in vitro¹. Sadly, high telomerase activity is correlated with the development of cancer, and the exploration of its use as an anti-aging therapy has thus been attenuated.

A recent study, published in the journal Cell, however, has explored the possibility of pumping-up telomerase activity in mice². The authors of this study enhanced telomerase activity in mice who had also been given a number of tumor-suppressing agents (p53, p16, and p19ARF) to render the rodents cancer resistant. This enhancement "improves the fitness of epithelial barriers, particularly the skin and the intestine, and produces a systemic delay in aging accompanied by extension of the median life span." (See figure, below.) The real significance of this study is that it is the first to demonstrate the ability of enhanced telomerase activity in extending lifespan in vivo, in a living organism.


from reference 2


Cells can only divide so many times before they become inviable (around 53 for humans). This hints at a fundamental limitation to the replication process. One component of this is surely that described herein of telomere shortening. However, there are many other ways that errors can accrue in DNA. On another note, it will be extremely intriguing to see how these sorts of aging stories regarding DNA and cell division relate to those concerning calorie restriction and associated metabolic pathways.

While the enhancement of telomerase activity is a piece of the aging puzzle, we have a long way to go in understanding the finite quality of cell division, and it may truly be inescapable, to say nothing of aging itself.

References:
1. Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu CP, Morin GB, Harley CB, Shay JW, Lichtsteiner S, Wright WE. Extension of life-span by introduction of telomerase into normal human cells. Science 279: 349-352, 1998.
2. Tomás-Loba A, Flores I, Fernández-Marcos PJ, Cayuela ML, Maraver A, Tejera A, Borrás C, Matheu A, Klatt P, Flores JM, Viña J, Serrano M, Blasco MA. Telomerase reverse transcriptase delays aging in cancer-resistant mice. Cell 135: 609-622, 2008.

On The Ways That Brains Change

from reference 1


It is well known that nervous system plasticity (the mutable quality of brains) underlies animals' ability to change their behaviors. However, it has been widely thought that such plasticity consists mostly of changes at synapses, the sites of communication between neurons, or in the intrinsic excitability of individual neurons - how likely a cell is to increase or decrease its voltage or to fire action potentials. New research challenges this view by showing that another type of alteration can be at work: single neurons can change the type of neurotransmitter they release in response to stimulation¹.

Specifically, this work addresses tadpole camouflage. Tadpoles can rapidly change (increase or decrease) the amount of pigmentation in their skin in order to blend in with their surroundings. The research I here refer to demonstrates that when frog tadpoles (Xenopus laevis) are stimulated with bright light, the number of dopamine-secreting (dopaminergic) neurons in the animals' brains increases, allowing them to adapt more rapidly to subsequent exposure to light.

When exposed to just hours of direct light, dark-reared tadpoles responded by doubling the number off dopaminergic neurons within a part of their central nervous system called the suprachiasmatic nucleus (SCN). Furthermore, these new dopaminergic neurons seem to integrate into the existing pathways for changing pigmentation. The authors were able to selectively destroy existing SCN dopaminergic neurons, eliminating the tadpoles ability to change pigment, and then rescue this ability with light exposure.

It remains unclear if this phenomenon is purely a developmental one, operating only prior to adulthood, an important caveat. None the less, the ability to change cell type is an as-yet unexplored form of neural plasticity which will have widespread implications for neuroscience research. Furthermore, this work may have even more direct application to human experience.

In human beings, the malfunction of certain dopamine-mediated signalling cascades (cell-level combinations of molecular interactions) have been implicated in seasonal affective disorder (winter depression). It is also well known that dopamine is intrinsically involved in the rewarding feelings delivered by food, sex and drugs. It may thus simply be the case that a lack of light stimulation leads to a lack of dopaminergic neurons, and thus to fewer episodes of rewarding experience during the winter months.

References:
1. Dulcis D, Spitzer NC. Illumination controls differentiation of dopamine neurons regulating behaviour. Nature 456: 195-201, 2008.

On Presidents and Science

I'm not the first by far to point this out, but I'm so happy that Barack Obama has been elected that I had to do something to mark the occasion. In fact I was totally oblivious to this imagistic event until Jessica excitedly picked up the magazine from my desk and proclaimed: "You have it!" Below are the front and back cover images from the September 25th issue of Nature magazine. It's not clear if this move was in any way intentional on the publisher's part, but it's pretty hilarious.

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On Art from Science

Copyright © 2005 Hunter O'Reilly


"Hunter O’Reilly obtained a Ph.D. in genetics from the University of Wisconsin-Madison and graduated cum laude from the University of California, Berkeley. Her abstractions have been shown internationally including galleries in New York, San Francisco, England, Italy, Japan, the Czech Republic, Indiana and Wisconsin."





"Observations in the laboratory and the world around her inspire the shapes in her abstract oil paintings. Hunter's abstract art hints at both organic matter at the highest level (human faces) and at the smallest level (single cells). This section includes many images of artwork."

"O'Reilly teaches biology and art at Loyola University Chicago. She created a course, Biology Through Art, where students have the opportunity to create innovative artworks in a biology laboratory. Students view microorganisms, use DNA as an artistic medium, create music based on DNA sequence and see anatomy as art. The course culminates in students creating their own biological self-portrait."

More images here.

On What's Possible

"... it's just over fifty years since the launch of Sputnik. This event started the "space race," and led President Kennedy to innaugurate the program to land men on the moon. Kennedy's prime motive was of course superpower rivalry -- cynics could deride it as a stunt. But it was an extraordinary technical triumph -- especially as NASA's total computing power was far less than that of a single mobile phone today." (my emphasis)

This is how we're investing our technological capital?

References:
1. Rees M. Science: The Coming Century. The New York Review of Books LV: 41-44, 2008.