[Fwd: More news on MIT Aging research]

Brian Atkins (brian@posthuman.com)
Sat, 27 Dec 1997 19:38:00 -0500

This is a multi-part message in MIME format.
Content-Type: text/plain; charset=us-ascii
Content-Transfer-Encoding: 7bit

The future has arrived; it's just not evenly distributed.
                                                       -William Gibson
Visit Hypermart at http://www.hypermart.net for free business hosting!
Content-Type: message/rfc822
Content-Transfer-Encoding: 7bit
Content-Disposition: inline

Return-Path: <owner-crsociety@lists.sni.net> Received: from hypermart.net (ns.hypermart.net []) by camel10.mindspring.com (8.8.5/8.8.5) with SMTP id PAA27273 for <jbatkins@mindspring.com>; Sat, 27 Dec 1997 15:23:20 -0500 (EST) Received: (qmail 9489 invoked by alias); 27 Dec 1997 20:26:28 -0000 Delivered-To: alias-posthumancom-brian@posthuman.com Received: (qmail 9484 invoked from network); 27 Dec 1997 20:26:27 -0000 Received: from lists.csn.net (HELO lists.sni.net) ( by ns.hypermart.net with SMTP; 27 Dec 1997 20:26:27 -0000 Received: (from majordo@localhost) by lists.sni.net (8.8.5/8.8.5) id NAA20887 for crsociety-include; Sat, 27 Dec 1997 13:06:43 -0700 (MST) Received: from SantaClara01.pop.internex.net (santaclara01.pop.InterNex.Net []) by lists.sni.net (8.8.5/8.8.5) with ESMTP id NAA20880 for <crsociety@lists.csn.net>; Sat, 27 Dec 1997 13:06:40 -0700 (MST) Received: from dellxpspro200 ([]) by SantaClara01.pop.internex.net (Post.Office MTA v3.1.2 release (PO203-101c) ID# 0-34792U7500L7500S0) with SMTP id AAA27231 for <crsociety@lists.csn.net>; Sat, 27 Dec 1997 12:06:39 -0800 Message-Id: <> X-Sender: infomaniac-1@SantaClara01.pop.internex.net X-Mailer: QUALCOMM Windows Eudora Pro Version 3.0.3 (32) Date: Sat, 27 Dec 1997 12:08:30 -0800 To: crsociety@lists.sni.net From: brianc@infomaniac.com (Brian Chiko) Subject: More news on MIT Aging research Mime-Version: 1.0 Content-Type: text/plain; charset="us-ascii" Sender: owner-crsociety@lists.sni.net Precedence: bulk

HEADLINE: Cell's mortal coils hold key to ageing

Scientists are beginning to understand how cells die, reports Nigel Hawkes

SCIENTISTS in the US have discovered an ageing mechanism in yeast cells that may one day make it possible to slow the process of human ageing.

They have found that the yeast cells become clogged with tiny coils of the genetic material DNA which break off from the chromosomes and proliferate until the cell becomes overwhelmed and dies. These "mortal coils " - to borrow from Shakespeare - appear to be responsible for the process of cell death, at least in this kind of cell.

"It is remarkable that this mechanism of ageing in yeast cells is so simple at the molecular level, " Professor Leonard Guarante and Dr David Sinclair of the Massachusetts Institute of Technology write in the journal Cell . "It is conceivable that inhibitors of this ageing process can be found and if so, such strategies might eventually prove useful in forestalling ageing in yeast and, perhaps, in higher organisms. "

The search for the elixir of youth is a recurrent theme of fiction, from the story of Faust to Oscar Wilde's The Picture of Dorian Gray . The desire for immortality has led to countless theories of ageing, but until recently little was actually known about how deterioration in function is related to cellular and molecular changes. However, earlier this year the MIT team identified a gene in Werner's Syndrome, a rare disease, whose carriers have symptoms resembling a speeded-up ageing process. They also showed that modifying that gene in yeast speeded ageing.

>From other yeast studies they found a series of genes that appear to determine lifespan, and found that the products of these genes moved into the nucleolus - a structure in the nucleus of the cell - implying that perhaps the nucleolus was the "Achilles' heel " of cells as they get older.

They found that the nucleolus eventually breaks up, preventing yeast cells from continuing to divide. The latest work identifies what it is that causes the nucleolus to grow larger and ultimately to fragment. This, the scientists say, is the accumulation of the DNA rings, which they call "extrachromosomal ribosomal DNA circles ", or ERCs. They are created from lengths of DNA pinched off from the chromosomes as the cell divides. They have found that the older the cell, the more ERCs it contains. Ultimately, they become so plentiful that they gum up the normal processes of cell division, and the cell dies.

The ERCs act as a kind of clock, Professor Guarente suggests. "Once an ERC is formed or inherited, the period of time until a lethal number of ERCs has accumulated may be the clock that determines the lifespan of the cell. "

ERCs can apparently form as a result of two processes. One is damage to DNA, which occurs all the time, and is usually efficiently repaired. The suggestion is that the ERCs are part of the repair process but, paradoxically, ultimately accumulate and cause cell death. But ERCs can also be inherited, suggesting that some cells are designed to have a built-in clock that limits their lifespan.

The implications of the research are that it may one day be possible to inhibit ageing in cells that are analogous to the yeast cells used in the experiments. In mammals, these are the so-called stem cells, found in organs such as the skin, kidney, liver and blood. The scientists say: "Next it will be important to determine whether ERCs or other circular DNAs accumulate in stem cells of ageing mice or humans. " =============================================

BYLINE: By Roger Highfield, Science Editor

BODY: THERE is more than a ring of truth in Hamlet's reference to the "mortal coil ", according to an article to be published today. An American team reports in the journal Cell that it has found a mechanism of ageing in yeast cells that suggests researchers may one day be able to intervene in, and possibly slow, the ageing process in certain human cells. The work marks the culmination of efforts by a team at the Massachusetts Institute of Technology in Boston that has shown that an aged yeast cell is full of small "mortal coils " called ERCs, which consist of coils of DNA. Now the hunt is on to find the DNA circles in aged human cells. The article, co-written by Dr David Sinclair and Prof Leonard Guarente, reveals a mechanism of ageing that the team says is "elegant in its simplicity ". "There is no certainty that these will be found in humans but it is certainly a possibility, " said Prof Guarente. During the life of a yeast cell, whenever a particular coiled piece of DNA pinches off from one of its chromosomes, the "extrachromosomal ribosomal DNA " or ERC replicates until the cell becomes overwhelmed and dies. Ageing begins in a yeast cell when the first ERC forms, although that does not seem to be at the start of its life. "They occur early in the lifespan of a mother cell and then accumulate by virtue of the fact that they can replicate, once formed, " said Prof Guarente. "When that cell divides, each circle of DNA replicates. Every time the cell doubles the number of ERCs double. " Prof Guarente says the ERC is like a clock in the yeast cell's mortality. "Set the clock early and the alarm rings early, " he said. The researchers suggest that the sheer abundance of ERCs could clog up components of the mother cells' replication machinery, leading to an inability to replicate the DNA necessary for life. "When a cell is old, the number of ERCs is very high, " he said. The biologists wrote: "It is conceivable that inhibitors of this [ageing] process can be found and if so, such strategies might eventually prove useful in forestalling ageing in yeast and, perhaps, in higher organisms. "