Navigation Links
Ticking of cellular clock promotes seismic changes in the chromatin landscape associated with aging
Date:10/3/2010

LA JOLLA, CA-Like cats, human cells have a finite number of lives-once they divide a certain number of times (thankfully, more than nine) they change shape, slow their pace, and eventually stop dividing, a phenomenon called "cellular senescence".

Biologists know that a cellular clock composed of structures at the chromosome end known as telomeres records how many "lives" a cell has expended. Up to now, investigators have not yet defined how the clock's ticking signals the approach of cellular oblivion.

In a study published in the Oct. 3, 2010, issue of Nature Structural and Molecular Biology, a team led by Jan Karlseder, Ph.D., at the Salk Institute for Biological Studies reports that as cells count down to senescence and telomeres wear down, their DNA undergoes massive changes in the way it is packaged. These changes likely trigger what we call "aging".

"Prior to this study we knew that telomeres get shorter and shorter as a cell divides and that when they reach a critical length, cells stop dividing or die," said Karlseder, an associate professor in the Molecular and Cell Biology Laboratory. "Something must translate the local signal at chromosome ends into a huge signal felt throughout the nucleus. But there was a big gap in between."

Karlseder and postdoctoral fellow Roddy O'Sullivan, Ph.D., began to close the gap by comparing levels of proteins called histones in young cells-cells that had divided 30 times-with "late middle-aged" cells, which had divided 75 times and were on the downward slide to senescence, which occurs at 85 divisions. Histone proteins bind linear DNA strands and compress them into nuclear complexes, collectively referred to as chromatin.

Karlseder and O'Sullivan found that aging cells simply made less histone protein than do young cells. "We were surprised to find that histone levels decreased as cells aged," said O'Sullivan, the study's first author. "These proteins are required throughout the genome, and therefore any event that disrupts this production line affects the stability of the entire genome."

The team then undertook exhaustive "time-lapse" comparisons of histones in young versus aging cells and confirmed that marked differences in the abundance and variety of histones were evident at every step as cells moved through cell division.

O'Sullivan calls the "default" histone pattern displayed by young cells "happy, healthy chromatin." By contrast, he says, aging cells appear to undergo stress as they duplicate their chromosomes in preparation for cell division and have difficulty restoring a "healthy" chromatin pattern once division is complete.

Comparisons of histone patterns in cells taken from human subjects-a 9- versus a 92-year-old-dramatically mirrored histone trends seen in cell lines. "These key experiments suggest that what we observe in cultured cells in a laboratory setting actually occurs and is relevant to aging in a population," says Karlseder.

The initiation of diseases associated with aging, such as cancer, is largely attributed to DNA, or genetic, damage. But this study suggests that aging itself is infinitely complex: that progressive telomere shortening hastens chromosomal aging by changing the way genes entwine with histones, so-called "epigenetic" changes. How DNA interacts with histones has enormous impact on whether genes are expressed-hence the current intense interest in the relationship of the epigenomic landscape to disease states.

Rescue experiments in which the team cosmetically enhanced aging cells confirmed that signals emitted by eroding telomeres drove epigenetic changes. When aging cells were engineered to express telomerase, the enzyme that restores and extends stubby telomeres, those rejuvenated cells showed histone levels reminiscent of "happy, healthy chromatin," and a partial return to a youthful chromatin profile.

Lest you sink your savings into schemes to elongate your telomeres, beware. "The flip side of elongating telomeres is that you enable cells to grow for much longer periods and can generate what are called "immortal" cells," says Karlseder. "That takes you one step closer to cancer cell development."

Up to now, the Karlseder lab has mostly focused on interactions between telomeres and DNA repair mechanisms. This paper now pushes them into the field of epigenetics. "We will continue to examine epigenetic changes in cells at different ages," says Karlseder. "We now want to determine if histone changes follow a linear process or whether they kick in as we age."


'/>"/>

Contact: Gina Kirchweger
kirchweger@salk.edu
858-453-410-01340
Salk Institute
Source:Eurekalert  

Related biology news :

1. Pitt/Iowa team finds cellular structural molecule can be toxic: Makes pneumonia worse
2. UCI-Scripps study links cellular motors to memory
3. Mount Sinai researchers discover new mechanism behind cellular energy conversion
4. SSRIs may pack more punch at the cellular level than believed
5. An IRCM researcher pinpoints the cellular mechanism responsible for modulating the permeability of blood vessels
6. A cellular housekeeper, and potential target of obesity drugs, caught in action
7. Origins of multicellularity: All in the family
8. Biologists identify a new clue into cellular aging
9. Researchers demystifying complex cellular communications hubs found in sensory neurons
10. Intracellular express -- why transport protein molecules have brakes
11. Cellular mechanical forces may initiate angiogenesis
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Ticking of cellular clock promotes seismic changes in the chromatin landscape associated with aging
(Date:5/24/2016)... Ampronix facilitates superior patient care by providing unparalleled technology to leaders of the medical ... premium product recently added to the range of products distributed by Ampronix. ... ... ... Ampronix News ...
(Date:5/12/2016)... , May 12, 2016 WearablesResearch.com , ... published the overview results from the Q1 wave of ... recent wave was consumers, receptivity to a program where ... with a health insurance company. "We were ... share," says Michael LaColla , CEO of Troubadour ...
(Date:4/28/2016)... and BANGALORE, India , April 28, ... Systems, a product subsidiary of Infosys (NYSE: INFY ... announced a global partnership that will provide end ... use mobile banking and payment services.      (Logo: ... key innovation area for financial services, but it also plays ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... BEACH, Calif. , June 23, 2016  Blueprint ... new biological discoveries to the medical community, has closed ... co-founder Matthew Nunez . "We have ... us with the capital we need to meet our ... will essentially provide us the runway to complete validation ...
(Date:6/23/2016)... Francisco, CA (PRWEB) , ... June 23, 2016 ... ... (EDC) software, is exhibiting at the Pennsylvania Convention Center and will showcase its ... Annual conference. ClinCapture will also be presenting a scientific poster on Disrupting Clinical ...
(Date:6/23/2016)... , June 22, 2016  Amgen (NASDAQ: ... of the QB3@953 life sciences incubator to ... health. The shared laboratory space at QB3@953 was created ... a key obstacle for many early stage organizations - ... of the sponsorship, Amgen launched two "Amgen Golden Ticket" ...
(Date:6/22/2016)... DUBLIN , June 22, 2016 Research ... and Global Markets" report to their offering. ... $39.4 billion in 2014 from $29.3 billion in 2013. The market ... (CAGR) of 13.8% from 2015 to 2020, increasing from $50.6 billion ... and projected product forecasts during the forecast period (2015 to 2020) ...
Breaking Biology Technology: