Where does the gene activity of youth go? New findings may hold the key
New evidence may explain why it is that we lose not only our youthful looks, but also our youthful pattern of gene activity with age. A report in the November 26th issue of the journal Cell, a Cell Press publication, reveals that a protein perhaps best known for its role in the life-extending benefits of a low-calorie diet also maintains the stability of the mammalian genome—the complete set of genetic instructions "written" in DNA.
The researchers found in studies of mammalian stem cells that the protein SIRT1 controls the packaging of DNA into chromatin, thereby setting the youthful pattern of gene activity by keeping select genes switched off. In response to DNA damage, those SIRT1 proteins leave their posts to go off and assist in the necessary repairs. That change in SIRT1's job description leads to shifts in gene activity that parallel those seen in the aging mouse brain, they show. They suspect similar changes would also be found in other body tissues as well.
" The critical protein controls both which genes are off and on as well as DNA repair; it's used for both processes, and that's the catch," said David Sinclair of Harvard Medical School. "As cells accumulate DNA damage, the protein can't do both jobs sufficiently." Once SIRT1 loses control, gene activity goes haywire, a state of affairs that leads to symptoms associated with aging.
Sinclair's team also found what they consider to be good evidence that the aging process can be slowed. Mice with an excess of SIRT1 had an improved ability to repair DNA and prevent those unwanted changes in gene expression. The hope is that those improvements could be reproduced with a drug that stimulates SIRT1, they said.
Indeed, the famous red wine ingredient known as resveratrol offers benefits through its effects on SIRT1, as do several more targeted drugs at some stage of development or testing. The new findings offer an explanation for how those life-promoting chemicals may be working. The ultimate test, Sinclair said, will be whether such drugs can indeed maintain a youthful gene profile.
While scientists had long known that gene activity changes with age, the driving force behind those changes remained mysterious, Sinclair said. Many had also proposed a connection between DNA damage and aging. After all, it's common knowledge that UV damage to the skin leaves it looking older. But again, he said, no one had really put their finger on just what the relationship is, or at least they hadn't in mammals.
In fact, scientists had discovered some years ago that Sir2, the yeast equivalent of SIRT1, stabilizes the genome. With age or in response to a DNA break, however, the Sir2 complex takes off for the damaged sites, activating genes that leave the yeast sterile, a characteristic associated with aging.
The new results show that the yeast aging process may be remarkably relevant to mammals. "If you step back and think, it's pretty striking," Sinclair said. "Something as simple as yeast can tell us about the mechanism of aging in mammals."
“You wait till Larry comes and I tell him my theory!” The bids, duly sealed, were given into the keeping of the commissary officer to be put in his safe, and kept until the day of judgment, when all being opened in public and in the presence of the aspirants, the lowest would[Pg 188] get the contract. It was a simple plan, and gave no more opportunity for underhand work than could be avoided. But there were opportunities for all that. It was barely possible—the thing had been done—for a commissary clerk or sergeant, desirous of adding to his pittance of pay, or of favoring a friend among the bidders, to tamper with the bids. By the same token there was no real reason why the commissary officer could not do it himself. Landor had never heard, or known, of such a case, but undoubtedly the way was there. It was a question of having the will and the possession of the safe keys. "Well, I believe our boys 's all right. They're green, and they're friskier than colts in a clover field, but they're all good stuff, and I believe we kin stand off any ordinary gang o' guerrillas. I'll chance it, anyhow. This's a mighty valuable train to risk, but it ought to go through, for we don't know how badly they may need it. You tell your engineer to go ahead carefully and give two long whistles if he sees anything dangerous." "Fine-looking lot of youngsters," he remarked. "They'll make good soldiers." "That's just what he was, the little runt, and we had the devil's own time finding him. What in Sam Hill did the Captain take him for, I'd like to know? Co. Q aint no nursery. Well, the bugler up at Brigade Headquarters blowed some sort of a call, and Skidmore wanted to know what it meant. They told him that it was an order for the youngest man in each company to come up there and get some milk for his coffee tomorrow morning, and butter for his bread. There was only enough issued for the youngest boys, and if he wanted his share he'd have to get a big hustle on him, for the feller whose nose he'd put out o' joint 'd try hard to get there ahead o' him, and get his share. So Skidmore went off at a dead run toward the sound of the bugle, with the boys looking after him and snickering. But he didn't come back at roll-call, nor at tattoo, and the smart Alecks begun to get scared, and abuse each other for setting up a job on a poor, innocent little boy. Osc Brewster and Ol Perry, who had been foremost in the trick had a fight as to which had been to blame. Taps come, and he didn't get back, and then we all became scared. I'd sent Jim Hunter over to Brigade Headquarters to look for him, but he came back, and said they hadn't seen anything of him there. Then I turned out the whole company to look for him. Of course, them too-awfully smart galoots of Co. A had to get very funny over our trouble. They asked why we didn't get the right kind of nurses for our company, that wouldn't let the members stray out of their sight? Why we didn't call the children in when the chickens went to roost, undress 'em, and tuck 'em in their little beds, and sing to 'em after they'd said 'Now I lay me down to sleep?' I stood it all until that big, hulking Pete Nasmith came down with a camp-kettle, which he was making ring like a bell, as he yelled out, 'Child lost! Child lost!' Behind him was Tub Rawlings singing, 'Empty's the cradle, baby's gone.' Then I pulled off my blouse and slung it into my tent, and told 'em there went my chevrons, and I was simply Scott Ralston, and able to lick any man in Co. A. One o' their Lieutenants came out and ordered them back to their quarters, and I deployed the company in a skirmish-line, and started 'em through the brush toward Brigade Headquarters. About three-quarters o' the way Osc Brewster and Ol Perry, when going through a thicket, heard a boy boo-hooing. They made their way to him, and there was little Skidmore sitting on a stump, completely confused and fagged out. He'd lost his way, and the more he tried to find it the worse he got turned around. They called out to him, and he blubbered out: 'Yes, it's me; little Pete Skidmore. Them doddurned fools in my company 've lost me, just as I've bin tellin' 'em right along they would, durn 'em.' Osc and Ol were so tickled at finding him that they gathered him up, and come whooping back to camp, carrying him every step of the way." And the rush stopped. Cadnan waited for a second, but there was no more. "Dara is not to die," he said. Then he saw Orion hanging over him, very low in the windy sky, shaking with frost. His eyes fixed themselves on the constellation, then gradually he became aware of the sides of a cart, of the smell of straw, of the movement of other bodies that sighed and stirred beside him. The physical experience was now complete, and soon the emotional had shaped itself. Memory came, rather sick. He remembered the fight, his terror, the flaming straw, the crowd that constricted and crushed him like a snake. His rage and hate rekindled, but this time without focus—he hated just everyone and everything. He hated the wheels which jolted him, his body because it was bruised, the other bodies round him, the stars that danced above him, those unknown footsteps that tramped beside him on the road. Farewell to Jane and Caroline!" HoME大香蕉色人阁
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