[ExI] Propensity for longer lifespan...

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http://www.sciencedaily.com/releases/2011/10/111020024333.htm


Propensity for Longer Life Span Inherited Non-Genetically Over Generations, Study Shows

ScienceDaily (Oct. 20, 2011) — We know that our environment -- what we eat, the
toxic compounds we are exposed to -- can positively or negatively impact our life
span. But could it also affect the longevity of our descendants, who may live under
very different conditions? Recent research from the Stanford University School of
Medicine suggests this could be the case.

Blocking or modifying the expression of any of three key proteins in a laboratory
roundworm increases the life span of not only the original animal, but also that
animal's descendents, the researchers found. This occurs even though the original
modification is no longer present in the descendants. The finding is the first to
show that longevity can be inherited in a non-genetic manner over several
generations.

It's tempting to translate the findings to humans, who share similar proteins with
those studied in the worms in this work. While much more investigation is needed,
the research at least hints at the possibility that modifications that occurred in
your great-grandparents, perhaps as a result of diet or other environmental
conditions, will affect your own life span.

"In some ways, this work relates to the idea of inheritance of acquired traits,
which is almost heretical because it has long been discounted by the laws of
Mendel," said associate professor of genetics Anne Brunet, PhD. "But we show in this
study that the transgenerational inheritance of longevity does occur in roundworms
via modulations of proteins that normally add epigenetic modifications to
chromatin."

Brunet is the senior author of the study, published online Oct. 19 in Nature. Former
graduate student Eric Greer (now a postdoctoral scholar at Harvard Medical School)
is the first author.

The term epigenetics describes a process by which organisms modulate their gene
expression in response to environmental cues without changing the underlying
sequence of their DNA. Chromatin, the tightly coiled complex of DNA and proteins
called histones that keeps the genetic material firmly packed in the cells' nucleus,
can be modified in an epigenetic manner by addition or removal of chemical tags on
histones or DNA itself. Although most chromatin modifications are reset between
generations during the process of reproduction, this study suggests that such
reprogramming is incomplete in some cases.

The current research builds on a previous study from Brunet's laboratory that showed
that mutations in several chromatin regulators can increase the life span of a
laboratory roundworm known as Caenorhabditis elegans by as much as 30 percent.
Interestingly, these chromatin regulators control life span by functioning at least
in part in the worm's reproductive system, or germ line. That research was published
in Nature last year.

Greer and Brunet wondered whether the effect on life span of these chromatin
regulators would be conveyed to the worms' descendants, even when the mutations were
no longer present. To answer this question, Greer individually mutated each of the
genes encoding three proteins -- ASH-2, WDR-5 and SET-2 -- involved in the chromatin
regulatory complex that adds methyl groups to a specific histone in chromatin. The
methyl groups work to lock chromatin in an open configuration that is accessible for
gene expression.

Greer then bred the worms in such a way that their descendants would no longer have
the mutations. He found that the descendants with normal levels of expression of
these three proteins (but with ancestors that were deficient for them) still lived
longer than descendants from un-mutated ancestors. This longer life span persisted,
in some cases for up to three generations, but did eventually disappear and the
worms reverted to a normal life span. When he compared the gene expression profiles
of long-lived descendants of mutant ancestors with those of control worms, Greer
found several hundred genes whose changes in expression were also inherited.

"We still don't know the exact mechanism of this epigenetic memory of longevity
between generations," said Brunet. "We hypothesize that when the parental generation
is missing key components that normally regulate chromatin, epigenetic marks are not
completely reset from one generation to the next in the germ line, thereby inducing
heritable changes in gene expression. It will be very interesting to understand how
this happens.

"We are also curious as to whether environmental factors that can affect longevity,
like calorie restriction, could also affect subsequent generations," she said.

In addition to Greer and Brunet, other Stanford researchers involved in the study
include postdoctoral scholars Travis Maures, PhD, Duygu Ucar, PhD, Elena Mancini,
PhD, and Bérénice Benayoun, PhD; graduate student Jana Lim; and undergraduate Anna
Hauswirth.

The research was supported by the National Institutes of Health, the Glenn
Foundation for Medical Research and a Helen Hay Whitney Postdoctoral Fellowship.

Journal Reference:

   1. Eric L. Greer, Travis J. Maures, Duygu Ucar, Anna G. Hauswirth, Elena Mancini,
Jana P. Lim, Bérénice A. Benayoun, Yang Shi, Anne Brunet. Transgenerational
epigenetic inheritance of longevity in Caenorhabditis elegans. Nature, 2011; DOI:
10.1038/nature10572