Category Archives: Transhuman News

PUBLIC RELEASE DATE:

8-May-2014

Contact: Karen Kreeger karen.kreeger@uphs.upenn.edu 215-349-5658 University of Pennsylvania School of Medicine

PHILADELPHIA - Ancient philosophers looked to alchemy for clues to life everlasting. Today, researchers look to their yeast. These single-celled microbes have long served as model systems for the puzzle that is the aging process, and in this week's issue of Cell Metabolism, they fill in yet another piece.

The study, led by researchers at the University of Pennsylvania, identifies a new molecular circuit that controls longevity in yeast and more complex organisms and suggests a therapeutic intervention that could mimic the lifespan-enhancing effect of caloric restriction, no dietary restrictions necessary. After all, says senior author Shelley Berger, PhD, "who wants to live on 500 calories a day?"

Berger, a Penn Integrates Knowledge Professor in the departments of Genetics and Cell and Developmental Biology at the Perelman School of Medicine and the department of Biology in the School of Arts and Sciences, studies epigenetics, the science of the control of genetic information. Epigenetics comprises multiple regulatory layers, including chromatin packaging -- the orderly wrapping of DNA around histone proteins in the cell nucleus. By altering this DNA packaging, cells can control when and how genes are expressed.

"Aging is, in part, the accumulation of cellular stress," she explains. "If you can better respond to these stresses, this ameliorates the damage it can cause."

Berger and her team looked for chromatin-associated genes that could influence longevity by searching for genes that already were implicated in epigenetic regulation that might extend lifespan when deleted in the yeast, Saccharomyces cerevisiae. One such gene improved lifespan by about 25 percent this would correspond to an increased lifespan in humans from 75 years to about 95 years a substantial benefit to longevity, notes Berger. The research, conducted by postdoctoral fellow Weiwei Dang, PhD, aimed to unravel how this increase in longevity was achieved and if it was related to cellular stress.

First, the team asked whether the gene ISW2 is part of previously identified longevity pathways, especially those associated with caloric restriction, a well-known strategy for extending lifespan. But pathways involving a form of chromatin modification (histone acetylation) came up empty, as did an alternate pathway involving growth control, suggesting ISW2 functions through a never-before-seen mechanism.

The team then looked for answers in the function of the ISW2 protein, and found that its absence alters the expression of genes involved in protecting cells from such stresses as DNA damage. Deletion of ISW2 increases the expression and activity of genes in DNA-damage repair pathways an effect also seen during calorie restriction.

Originally posted here:
Penn yeast study identifies novel longevity pathway

Ancient philosophers looked to alchemy for clues to life everlasting. Today, researchers look to their yeast. These single-celled microbes have long served as model systems for the puzzle that is the aging process, and in this week's issue of Cell Metabolism, they fill in yet another piece.

The study, led by researchers at the University of Pennsylvania, identifies a new molecular circuit that controls longevity in yeast and more complex organisms and suggests a therapeutic intervention that could mimic the lifespan-enhancing effect of caloric restriction, no dietary restrictions necessary. After all, says senior author Shelley Berger, PhD, "who wants to live on 500 calories a day?"

Berger, a Penn Integrates Knowledge Professor in the departments of Genetics and Cell and Developmental Biology at the Perelman School of Medicine and the department of Biology in the School of Arts and Sciences, studies epigenetics, the science of the control of genetic information. Epigenetics comprises multiple regulatory layers, including chromatin packaging -- the orderly wrapping of DNA around histone proteins in the cell nucleus. By altering this DNA packaging, cells can control when and how genes are expressed.

"Aging is, in part, the accumulation of cellular stress," she explains. "If you can better respond to these stresses, this ameliorates the damage it can cause."

Berger and her team looked for chromatin-associated genes that could influence longevity by searching for genes that already were implicated in epigenetic regulation that might extend lifespan when deleted in the yeast, Saccharomyces cerevisiae. One such gene improved lifespan by about 25 percent -- this would correspond to an increased lifespan in humans from 75 years to about 95 years -- a substantial benefit to longevity, notes Berger. The research, conducted by postdoctoral fellow Weiwei Dang, PhD, aimed to unravel how this increase in longevity was achieved and if it was related to cellular stress.

First, the team asked whether the gene ISW2 is part of previously identified longevity pathways, especially those associated with caloric restriction, a well-known strategy for extending lifespan. But pathways involving a form of chromatin modification (histone acetylation) came up empty, as did an alternate pathway involving growth control, suggesting ISW2 functions through a never-before-seen mechanism.

The team then looked for answers in the function of the ISW2 protein, and found that its absence alters the expression of genes involved in protecting cells from such stresses as DNA damage. Deletion of ISW2 increases the expression and activity of genes in DNA-damage repair pathways -- an effect also seen during calorie restriction.

The gene ISW2, it turns out, is involved in chromatin remodeling -- it controls the spacing and distribution of the histone "spools" around which DNA wraps. Normally, ISW2 dampens stress-response pathways, possibly because overactivation of these pathways is deleterious early in life, Berger speculates. Deletion or inactivation of the ISW2 gene activates those pathways, priming the cells to more effectively handle stress-associated genetic scars as cells age.

This effect is not limited to yeast. When Berger's team reduced the levels of a related gene in the nematode worm, Caenorhabditis elegans, they observed a 15 percent improvement in longevity, which is similar in magnitude to the lifespan extension observed in other worm longevity pathways. Similarly, knocking down expression of a human homolog in cultured human cells boosted the expression of stress-response genes that, again, like yeast, occur in DNA-damage repair pathways.

These findings suggest a pathway analogous to the one identified in yeast performs a similar function in humans, keeping stress-response genes in check -- and if inhibited, could boost these pathways. But that has yet to be established. And, it is far from clear if tweaking these pathways can actually extend healthy human lifespan -- but, of course, a goal worthy of further investigation, say the authors.

Read more from the original source:
Yeast study identifies novel longevity pathway

The plague preferentially killed the very old and those already in poor health. Natural selection or better diets may have allowed those who remained to thrive

A depiction of the black death from a 15th-century Bible

The Black Death, a plague that first devastated Europe in the 1300s, had a silver lining. After the ravages of the disease, surviving Europeans lived longer, a new study finds.

An analysis of bones in London cemeteries from before and after the plague reveals that people had a lower risk of dying at any age after the first plague outbreak compared with before. In the centuries before the Black Death, about 10 percent of people lived past age 70, said study researcher Sharon DeWitte, a biological anthropologist at the University of South Carolina. In the centuries after, more than 20 percent of people lived past that age.

"It is definitely a signal of something very important happening with survivorship," DeWitte told Live Science. [Images: 14th-Century Black Death Graves]

The plague years

The Black Death, caused by the Yersinia pestis bacterium, first exploded in Europe between 1347 and 1351. The estimated number of deaths ranges from 75 million to 200 million, or between 30 percent and 50 percent of Europe's population. Sufferers developed hugely swollen lymph nodes, fevers and rashes, and vomited blood. The symptom that gave the disease its name was black spots on the skin where the flesh had died.

Scientists long believed that the Black Death killed indiscriminately. But DeWitte's previous research found the plague was like many sicknesses: It preferentially killed the very old and those already in poor health.

That discovery raised the question of whether the plague acted as a "force of selection, by targeting frail people," DeWitte said. If people's susceptibility to the plague was somehow genetic perhaps they had weaker immune systems, or other health problems with a genetic basis then those who survived might pass along stronger genes to their children, resulting in a hardier post-plague population.

In fact, research published in February in the journal Proceedings of the National Academy of Sciences suggested that the plague did write itself into human genomes: The descendants of plague-affected populations share certain changes in some immune genes.

See the original post:
Black Death Survivors and Their Descendants Went On to Live Longer