Effects of aging in stem cells
July 24, 2007
Aging HSCs exhibit a functional decline (yet an increase in cell number) and display a heightened stress and inflammatory response along with signs of epigenetic erosion. Credit: Image: S. M. Chambers
There is little disagreement that the body’s maintenance and repair systems deteriorate with age, even as there is plenty of disagreement as to why. Stem cells combat the aging process by replenishing old or damaged cells—particularly in the skin, gut, and blood—with a fresh supply to maintain and repair tissue. Unfortunately, new evidence published in the open-access journal PLoS Biology suggests that this regenerative capacity also declines with age as stem cells acquire functional defects.
Stuart Chambers, Margaret Goodell, and their colleagues investigated the molecular mechanisms underlying aging of stem cells by looking at the gene expression profiles of aging hematopoietic stem cells (HSCs), the precursors of blood cells. They found that genes involved in the inflammatory and stress response became more active with age, while genes important for regulating gene expression and genomic integrity became less active. These results lend strong support to the notion that HSCs succumb to the wear and tear of aging, just like other cells, and shed light on the mechanisms of aging.
To study HSCs’ regenerative capacity over time, Chambers et al. isolated HSCs from young (aged 2 months) and old (aged 21 months) mice and then transplanted either young or old cells into mice whose bone marrow cells had been destroyed by radiation. The young and old HSCs gave rise to new marrow cells at roughly the same pace 4 weeks after transplantation. But at 8 and 16 weeks after transplantation, the old HSCs’ contributions had dropped considerably, suggesting that aging HSCs lose their repopulating capacity. Yet, because HSCs increased in number, overall blood production from HSCs remained stable.
The finding that genes involved in the inflammatory response are expressed more (called up-regulation) as HSCs age fits with evidence linking inflammation and aging in the kidney, brain, and arteries. It may also help explain why HSCs lose function. One of the up-regulated genes, P-selectin, encodes a cell surface adhesion molecule. Because transplanted HSCs depend on cell adhesion to colonize bone marrow properly, the researchers explain, inappropriate up-regulation of genes encoding P-selectin may interfere with this process.
The markedly reduced expression (or down-regulation) of genes involved in chromatin remodeling, an “epigenetic” regulator of gene expression, suggested that transcriptional activity might be dysregulated across the genome.
Though the dominant model attributes the physical effects of aging to an accretion of isolated genetic insults, these results link age-related decline to global mechanisms operating across the genome. In the researchers’ “epigenetic view of aging,” chromatin dysregulation provides a logical explanation for the numerous and diverse age-related changes observed at the molecular, cellular, and organismal levels. Over the normal course of aging, chromatin dysregulation leads to dysregulation of many genes, which in turn leads to a loss of normal cellular functions and a loss of growth regulation. These changes ultimately increase the risk of cancer, which, in many of its forms, increases dramatically with age. Future studies can investigate how epigenetic regulation, inflammation, and the stress response interact to better understand the molecular mechanisms of aging, and why so many of us face a high risk of cancer in our later years.
Source: Public Library of Science
-
Aging stem cells may explain higher prevalence of leukemia, infections among elderly
Nov 28, 2011 |
3 / 5 (2) |
0
-
Unappreciated dynamism of blood cell production
Feb 07, 2011 |
4 / 5 (1) |
0
-
Adult stem cells may be beneficial for certain cardiovascular disorders and autoimmune diseases
Feb 26, 2008 |
3 / 5 (1) |
0
-
Engineers build first sub-10-nm carbon nanotube transistor
Feb 01, 2012 |
4.9 / 5 (31) |
30
-
Something old, something new: Evolution and the structural divergence of duplicate genes
Jan 31, 2012 |
4.6 / 5 (7) |
1
-
The hidden nanoworld of ice crystals: Revealing the dynamic behavior of quasi-liquid layers
Jan 30, 2012 |
5 / 5 (3) |
1
-
Stock market network reveals investor clustering
Jan 27, 2012 |
3.9 / 5 (23) |
8
-
Of microchemistry and molecules: Electronic microfluidic device synthesizes biocompatible probes
Jan 26, 2012 |
5 / 5 (1) |
0
More news stories
The power of estrogen -- male snakes attract other males
A new study has shown that boosting the estrogen levels of male garter snakes causes them to secrete the same pheromones that females use to attract suitors, and turned the males into just about the sexiest ...
9 hours ago |
5 / 5 (3) |
0
|
Grass to gas: Researchers' genome map speeds biofuel development
Researchers at the University of Georgia have taken a major step in the ongoing effort to find sources of cleaner, renewable energy by mapping the genomes of two originator cells of Miscanthus x giganteus, a large perenn ...
6 hours ago |
3.7 / 5 (3) |
0
|
Experts reveal how plants don't get sunburn
(PhysOrg.com) -- Experts at the University of Glasgow have discovered how plants survive the harmful rays of the sun.
9 hours ago |
5 / 5 (2) |
0
|
Protein libraries in a snap
(PhysOrg.com) -- A Rice University undergraduate will depart with not only a degree but also a possible patent for his invention of an efficient way to create protein libraries, an important component of biomolecular ...
12 hours ago |
5 / 5 (2) |
0
|
Miami battling invasion of giant African snails
No one knows how they got there. But an invasion of African giant snails has southern Florida in a panic over potential crop damage, disease and general yuckiness surrounding the slimy gastropods.
13 hours ago |
4 / 5 (1) |
4
Google users warned of threat to smartphone wallets
Users of Google smartphone wallets were being warned on Friday that there is a way to crack pass codes intended to thwart thieves from going on illicit shopping sprees.
Anonymous knocks CIA website offline (Update)
The website of the Central Intelligence Agency was inaccessible on Friday after the hacker group Anonymous claimed to have knocked it offline.
Complex wiring of the nervous system may rely on a just a handful of genes and proteins
Researchers at the Salk Institute have discovered a startling feature of early brain development that helps to explain how complex neuron wiring patterns are programmed using just a handful of critical genes. ...
NASA sees wide-eyed cyclone Jasmine
Cyclone Jasmine's eye has opened wider on NASA satellite imagery, as it moves through the Southern Pacific Ocean.
NASA sees Giovanna reach cyclone strength, threaten Madagascar
Tropical Storm 12S built up steam and became a cyclone on February 10, 2012 as NASA's Terra satellite passed overhead. Residents of east-central Madagascar should prepare for this cyclone to make landfall ...
Putting the squeeze on planets outside our solar system
(PhysOrg.com) -- Using high-powered lasers, scientists at Lawrence Livermore National Laboratory and collaborators discovered that molten magnesium silicate undergoes a phase change in the liquid state, abruptly ...