Ouroboros: Research in the biology of aging

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Ouroboros is a community weblog for biologists of aging. The mission of the site is to provide timely, thoughtful and scholarly commentary on developments within the field, as they are reported in the literature and at relevant conferences.

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  • February 23, 2010
  • 04:54 PM

A conflict between exercise and longevity control?

by ouroboros in Ouroboros: Research in the biology of aging

We know that exercise is good for us, and increasingly we’re understanding how it works at the molecular and cellular level: Physical activity boosts levels of heat shock proteins, which help cells resist stress; it also improves mitochondrial function in a manner reminiscent of calorie restriction (CR). Our knowledge is sophisticated enough that we can [...]... Read more »

Fry, C., Glynn, E., Drummond, M., Timmerman, K., Fujita, S., Abe, T., Dhanani, S., Volpi, E., & Rasmussen, B. (2010) Blood flow restriction exercise stimulates mTORC1 signaling and muscle protein synthesis in older men. Journal of Applied Physiology. DOI: 10.1152/japplphysiol.01266.2009  

  • February 16, 2010
  • 03:52 AM

SIRT3: fighting cancer in the mitochondria

by ouroboros in Ouroboros: Research in the biology of aging

Yesterday we learned that the most well-characterized mammalian sirtuin, SIRT1, is involved in the control of behavior in response to food availability. SIRT1 is just one of seven sirtuins in mammalian genomes, each of which has a characteristic expression pattern, subcellular localization, and physiological importance.
Today we’re going to talk about another member of the [...]... Read more »

  • February 15, 2010
  • 03:36 AM

SIRT1 on the brain: Sirtuin controls behavior under CR

by ouroboros in Ouroboros: Research in the biology of aging

Not only does the mammalian sirtuin SIRT1 mediate the lifespan extension phenotype of caloric restriction (CR), it is also involved in controlling behavior (such as food intake) in response to CR (and possibly during ad libitum feeding as well).
Two recent papers with consistent results address the issue. Both studies employed brain-specific knockouts of SIRT1; [...]... Read more »

Çakir, I., Perello, M., Lansari, O., Messier, N., Vaslet, C., & Nillni, E. (2009) Hypothalamic Sirt1 Regulates Food Intake in a Rodent Model System. PLoS ONE, 4(12). DOI: 10.1371/journal.pone.0008322  

  • February 12, 2010
  • 03:20 AM

As the worm turns

by ouroboros in Ouroboros: Research in the biology of aging

A couple of worm genomics papers caught my eye this week.
One is about using networks of genes as biomarkers. (The first author is our own turritopsis, and we extend our heartiest congratulations on the publication of this interesting paper.) It’s a neat idea: networks make better biomarkers than single genes; furthermore, thinking about genes [...]... Read more »

  • February 11, 2010
  • 03:28 AM

Yet another reason to like vitamin C

by ouroboros in Ouroboros: Research in the biology of aging

The hottest thing in stem cells right now is induced pluripotency, i.e., converting somatic cells back into pluripotent cells by introducing a few stem cell-specific genes (or even the encoded proteins). Induced pluripotent stem cells (iPS) harvested from a donor’s skin would be automatically immunologically matched; furthermore, they completely circumvent some of the “ethical” and [...]... Read more »

Esteban, M., Wang, T., Qin, B., Yang, J., Qin, D., Cai, J., Li, W., Weng, Z., Chen, J., & Ni, S. (2010) Vitamin C Enhances the Generation of Mouse and Human Induced Pluripotent Stem Cells. Cell Stem Cell, 6(1), 71-79. DOI: 10.1016/j.stem.2009.12.001  

  • February 10, 2010
  • 03:45 AM

Metformin: an anti-diabetic drug that is also anti-aging?

by ouroboros in Ouroboros: Research in the biology of aging

To the growing list of small-molecule drugs that have a measurable effect on lifespan or healthspan (e.g., resveratrol and rapamycin) we should add metformin, an anti-diabetic drug that has shown promise as a calorie restriction mimetic. Onken & Driscoll determined some of the genetic requirements for metformin’s anti-aging properties in the worm C. elegans:

Metformin induces [...]... Read more »

  • February 9, 2010
  • 04:04 PM

I’ll never be like you: Daughter cells send toxic aggregates back to mom

by ouroboros in Ouroboros: Research in the biology of aging

Cells tend to produce unwanted protein aggregates and other molecular refuse slightly faster than they can get rid of it, resulting in a time-dependent accumulation of potentially toxic cellular garbage. This, in turn, can cause an age-dependent loss of cellular viability, which is (in certain contexts) a fair operational definition of aging.
How can cells deal [...]... Read more »

  • February 8, 2010
  • 02:56 PM

Mazel tov! You should have such long telomeres

by ouroboros in Ouroboros: Research in the biology of aging

A study of Ashkenazi Jewish centenarians by Atzmon et al. has revealed that telomere length is correlated with longer lifespan and slower biological aging (reflected in measurements of several biomarkers of aging). Both lifespan and telomere length are, in turn, correlated with polymorphisms at the hTERT and hTERC loci, two genes that respectively encode the [...]... Read more »

Atzmon, G., Cho, M., Cawthon, R., Budagov, T., Katz, M., Yang, X., Siegel, G., Bergman, A., Huffman, D., Schechter, C.... (2009) Evolution in Health and Medicine Sackler Colloquium: Genetic variation in human telomerase is associated with telomere length in Ashkenazi centenarians. Proceedings of the National Academy of Sciences, 107(suppl_1), 1710-1717. DOI: 10.1073/pnas.0906191106  

  • September 17, 2009
  • 02:22 PM


by ouroboros in Ouroboros: Research in the biology of aging

A prominent scholar of the CLK-1 story has called the coroner on the mitochondrial free radical theory of aging (MFRTA). From Lapointe & Hekimi:

When a theory of aging ages badly
According to the widely acknowledged mitochondrial free radical theory of aging (MFRTA), the macromolecular damage that results from the production of toxic reactive oxygen species [...]... Read more »

Lapointe, J., & Hekimi, S. (2009) When a theory of aging ages badly. Cellular and Molecular Life Sciences. DOI: 10.1007/s00018-009-0138-8  

  • June 17, 2009
  • 12:59 AM

Sexing up the soma: Long-lived mutants express germ line genes in somatic tissues

by ouroboros in Ouroboros: Research in the biology of aging

We are all descendents of an unbroken line of cell divisions, dating back to the last common ancestor of all life on Earth. At some point, long after our lineage had acquired features like nuclei and mitochondria, a less distant ancestor stumbled on a major innovation: it grew a body, bringing with it the advantages [...]... Read more »

  • June 11, 2009
  • 03:54 PM

Unfolding the role of the hypoxic response in aging

by ouroboros in Ouroboros: Research in the biology of aging

The TOR (”target of rapamycin”) protein is a master regulator of cell growth, governing connect nutrient sensing, protein synthesis, and proliferation. It has become increasingly clear that the TOR pathway plays an essential role in longevity determination — specifically, higher TOR activity is associated with more rapid aging and shorter lifespan.

In mammals, TOR interferes [...]... Read more »

  • June 4, 2009
  • 05:07 AM

Did aging evolve to prevent epidemics?

by ouroboros in Ouroboros: Research in the biology of aging

How did aging evolve? Some evolutionary theories invoke tradeoffs between maintenance/repair and reproduction. Others postulate that genes that cause age-related decline can be positively selected, so long as these same genes confer a fitness advantage early in life.

A common feature of these theories is that they operate at the level of the individual organism, [...]... Read more »

  • June 4, 2009
  • 04:01 AM

“What if you could think a thought at the world and have the world think back?”

by ouroboros in Ouroboros: Research in the biology of aging

In collaboration with the estimable Vivan Siegel, I’m writing a series of op/ed articles on the future of scientific publishing. The first of these was about the challenges of filtering the scientific literature. The second piece, explores the prospect of using “Web 2.0″ approaches to accelerate scientific progress. The article starts from the assumption that [...]... Read more »

  • June 2, 2009
  • 04:29 PM

Found in (mis)translation: A novel role for protein synthesis fidelity in aging

by ouroboros in Ouroboros: Research in the biology of aging

The idea that translation fidelity might play a role in aging dates back at least as far as 1963, when Leslie Orgel proposed the “error catastrophe” theory of aging: in this model, mistranslation of the translational machinery creates a feedback loop that leads to further translation errors, ultimately causing loss of cell viability. From the [...]... Read more »

Silva, R., Duarte, I., Paredes, J., Lima-Costa, T., Perrot, M., Boucherie, H., Goodfellow, B., Gomes, A., Mateus, D., Moura, G.... (2009) The Yeast PNC1 Longevity Gene Is Up-Regulated by mRNA Mistranslation. PLoS ONE, 4(4). DOI: 10.1371/journal.pone.0005212  

  • May 29, 2009
  • 02:12 PM

Extending lifespan while shortening healthspan?

by ouroboros in Ouroboros: Research in the biology of aging

One of the central precepts of biogerontology is that meaningful lifespan extension will be concomitant with extension of the “healthspan”, i.e., the vigorous part of life — life that is, for lack of a better phrase, worth living.

This relationship is borne out both in nature (where longer-lived organisms also have longer healthspans) and in [...]... Read more »

  • May 28, 2009
  • 04:21 AM

The free radical theory of aging: A retrospective by its creator

by ouroboros in Ouroboros: Research in the biology of aging

The free radical theory of aging (FRTA) was first advanced by Denham Harman more than 50 years ago. The theory proceeds logically from a small number of straightforward assumptions, based on observations from radiation biology. From the Science of Aging Timeline:

Harman’s logic proceeds from three observations: (1) irradiation causes premature aging; (2) irradiation creates oxygen [...]... Read more »

  • May 19, 2009
  • 06:38 AM

Using human gene expression profiles to predict longevity

by turritopsis in Ouroboros: Research in the biology of aging

Recently, some human survival data – together with matching gene expression data from lymphoblastoid cell lines – have become available from a long-range study that began in the early 1980s. In the first aging study to take advantage of this resource, Kerber et al. mine the data to identify gene changes associated with longevity:... Read more »

  • May 11, 2009
  • 04:45 AM

Autophagy vs. cholesterol

by ouroboros in Ouroboros: Research in the biology of aging

Over at Fight Aging!, Reason has penned a very nice piece of analysis on a recent article demonstrating that stimulation of one autophagic pathway can reduce plasma lipoproteins and triglycerides. From the blog post:

A Tangible Benefit of Artificially Boosting Autophagy

The researchers used a compound to block lipolysis in order to provoke greater levels of autophagy [...]... Read more »

Straniero, S., Cavallini, G., Donati, A., Pallottini, V., Martini, C., Trentalance, A., & Bergamini, E. (2009) Stimulation of Autophagy by Antilipolytic Drugs May Rescue Rodents from Age-Associated Hypercholesterolemia. Rejuvenation Research, 12(2), 77-84. DOI: 10.1089/rej.2008.0806  

  • May 7, 2009
  • 04:18 AM

Choke on this: The hypoxia pathway extends lifespan and reduces proteotoxicity

by ouroboros in Ouroboros: Research in the biology of aging

Protein degradation is an essential longevity assurance pathway. Maintaining high levels of autophagy can delay age-related decline in liver function. Obstacles to protein degradation tend to shorten the lifespan: blocking autophagy causes hypersensitivity to stress, and inhibiting the ubiquitin/proteasome pathway damages the mitochondria; both of these treatments kill neurons.

Conversely, longevity enhancement tends to enhance [...]... Read more »

Mehta, R., Steinkraus, K., Sutphin, G., Ramos, F., Shamieh, L., Huh, A., Davis, C., Chandler-Brown, D., & Kaeberlein, M. (2009) Proteasomal Regulation of the Hypoxic Response Modulates Aging in C. elegans. Science. DOI: 10.1126/science.1173507  

  • April 30, 2009
  • 04:01 AM

Giving DAF-16 the upper hand: a transcriptional switch in the IGF pathway?

by ouroboros in Ouroboros: Research in the biology of aging

The insulin-like growth factor (IGF) pathway is one of the longest-known and well-studied regulators of longevity. Extracellular signals (insulin-like peptides) activate insulin-receptor homologs (in worm, DAF-2) which in turn recruit and activate phosphoinositol 3-kinases (AGE-1). PI3Ks convert PIP2 into PIP3, which tethers and recruits other kinases such as AKT-1. Eventually, activation of these upstream kinases [...]... Read more »

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