24 posts · 7,689 views
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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- September 17, 2009
- 01:22 PM
- 671 views
RIP for MFRTA?
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
- May 29, 2009
- 01:12 PM
- 487 views
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 »
Avanesian, A., Khodayari, B., Felgner, J., & Jafari, M. (2009) Lamotrigine extends lifespan but compromises health span in Drosophila melanogaster. Biogerontology. DOI: 10.1007/s10522-009-9227-1
- April 29, 2009
- 03:01 AM
- 480 views
Inhibiting mitochondrial respiration delays aging: CLK-1 and the retrograde response
by ouroboros in Ouroboros: Research in the biology of aging
The CLK-1 gene is a longevity regulator that has been conserved across evolution: loss of function in both C. elegans (where the gene was first described) and hemizygosity in mouse (where the gene is called mCLK1) results inincreased lifespan (though at a cost to evolutionary fitness). Consistent with this, at least one anti-neurodegeneration drug inhibits [...]... Read more »
Cristina, D., Cary, M., Lunceford, A., Clarke, C., & Kenyon, C. (2009) A Regulated Response to Impaired Respiration Slows Behavioral Rates and Increases Lifespan in Caenorhabditis elegans. PLoS Genetics, 5(4). DOI: 10.1371/journal.pgen.1000450
- May 28, 2009
- 03:21 AM
- 470 views
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 »
Harman, D. (2009) Origin and evolution of the free radical theory of aging: a brief personal history, 1954–2009. Biogerontology. DOI: 10.1007/s10522-009-9234-2
- May 7, 2009
- 03:18 AM
- 469 views
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
- 03:01 AM
- 441 views
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 »
Tazearslan, C., Ayyadevara, S., Bharill, P., & Shmookler Reis, R. (2009) Positive Feedback between Transcriptional and Kinase Suppression in Nematodes with Extraordinary Longevity and Stress Resistance. PLoS Genetics, 5(4). DOI: 10.1371/journal.pgen.1000452
- April 6, 2009
- 04:27 PM
- 437 views
Mining expression data to identify robust patterns of age-dependent regulation
by ouroboros in Ouroboros: Research in the biology of aging
In recent years, dozens of large-scale gene expression studies (many of them available through the Gene Aging Nexus) have tracked the transcriptional changes that occur with aging. However, these studies usually identify few genes showing statistically significant changes; worse, there is poor overlap across studies – i.e. genes found to be very significant in one [...]... Read more »
de Magalhaes, J., Curado, J., & Church, G. (2009) Meta-analysis of age-related gene expression profiles identifies common signatures of aging. Bioinformatics, 25(7), 875-881. DOI: 10.1093/bioinformatics/btp073
- June 4, 2009
- 03:01 AM
- 431 views
“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 »
Patil, C., & Siegel, V. (2009) This revolution will be digitized: online tools for radical collaboration. Disease Models and Mechanisms, 2(5-6), 201-205. DOI: 10.1242/dmm.003285
- June 4, 2009
- 04:07 AM
- 431 views
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 »
Mitteldorf, J., & Pepper, J. (2009) Senescence as an adaptation to limit the spread of disease. Journal of Theoretical Biology. DOI: 10.1016/j.jtbi.2009.05.013
- June 16, 2009
- 11:59 PM
- 429 views
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 »
Curran, S., Wu, X., Riedel, C., & Ruvkun, G. (2009) A soma-to-germline transformation in long-lived Caenorhabditis elegans mutants. Nature. DOI: 10.1038/nature08106
- June 2, 2009
- 03:29 PM
- 427 views
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
- April 1, 2009
- 01:24 PM
- 425 views
Mitochondrial DNA replication and progeroid symptoms
by ouroboros in Ouroboros: Research in the biology of aging
Nuclear DNA repair mutants exhibit progeroid symptoms. There are many types of DNA damage, and, accordingly, we have evolved mechanisms to deal with each type of damage. Nucleotide excision repair removes bulky adducts, and base excision repair removes damaged bases. Mismatch repair fixes nucleotides that aren’t matched in their correct A:T/G:C configuration. [...]... Read more »
Bailey, L., Cluett, T., Reyes, A., Prolla, T., Poulton, J., Leeuwenburgh, C., & Holt, I. (2009) Mice expressing an error-prone DNA polymerase in mitochondria display elevated replication pausing and chromosomal breakage at fragile sites of mitochondrial DNA. Nucleic Acids Research. DOI: 10.1093/nar/gkp091
- May 11, 2009
- 03:45 AM
- 425 views
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
- March 30, 2009
- 03:27 AM
- 407 views
FOXO3A polymorphisms linked to human longevity - again!
by ouroboros in Ouroboros: Research in the biology of aging
In my first contribution to Ouroboros, I reviewed a paper in which the authors found an allele of FOXO3A associated with long lived Japanese men. So it seemed highly appropriate that I wrote the review for a follow-up paper: Flachsbart et al. analyzed 16 polymorphisms in the FOXO3A allele in 1,031 long-lived individuals (95-110 years [...]... Read more »
Flachsbart, F., Caliebe, A., Kleindorp, R., Blanche, H., von Eller-Eberstein, H., Nikolaus, S., Schreiber, S., & Nebel, A. (2009) Association of FOXO3A variation with human longevity confirmed in German centenarians. Proceedings of the National Academy of Sciences, 106(8), 2700-2705. DOI: 10.1073/pnas.0809594106
- June 11, 2009
- 02:54 PM
- 407 views
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 »
Chen, D., Thomas, E., & Kapahi, P. (2009) HIF-1 Modulates Dietary Restriction-Mediated Lifespan Extension via IRE-1 in Caenorhabditis elegans. PLoS Genetics, 5(5). DOI: 10.1371/journal.pgen.1000486
- May 19, 2009
- 05:38 AM
- 361 views
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 »
Kerber, R., O’Brien, E., & Cawthon, R. (2009) Gene expression profiles associated with aging and mortality in humans. Aging Cell, 8(3), 239-250. DOI: 10.1111/j.1474-9726.2009.00467.x
- February 10, 2010
- 02:45 AM
- 73 views
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 »
Onken, B., & Driscoll, M. (2010) Metformin Induces a Dietary Restriction–Like State and the Oxidative Stress Response to Extend C. elegans Healthspan via AMPK, LKB1, and SKN-1. PLoS ONE, 5(1). DOI: 10.1371/journal.pone.0008758
- February 23, 2010
- 03:54 PM
- 70 views
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 8, 2010
- 01:56 PM
- 64 views
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
- February 11, 2010
- 02:28 AM
- 64 views
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
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