Methuselah Fly Died Today

Started by dnamechanic , Jun 17 2005 01:10 AM

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#1 dnamechanic

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Posted 17 June 2005 - 01:10 AM

Methuselah fly was 131 days old today.

He was a transgenic fly, he had some extra DNA sequences in his genome.

His group, and his control groups lived their life at standard lab conditions; 25 degrees C. and 50% humidity.

The median lifespan of Methuselah's group was 76.6 days.

The most robust group, of his control groups, had a median lifespan of 60.2 days.
The longest living of the control flies lived to an age of 103 days.

Methuselah was feeble this morning. I had him pose for the photograph below.
Other members of the lab think the extra stress was detrimental for him.

He died later, today.

Methuselah and his experimental cohorts have provided some interesting data (more details later).

Rest in peace, Methuselah fly.

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MethuselahFly.jpg 15.66KB 0 downloads

Edited by dnamechanic, 17 June 2005 - 01:33 AM.

#2

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Posted 17 June 2005 - 01:14 AM

Great post! How was the long lived cohort's genome altered?

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#3 dnamechanic

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Posted 17 June 2005 - 01:52 AM

Hi Prometheus,

Glad you liked Methuselah fly.

He was a transgenic fly via P-element insertion. He had an extra gene for a certain small protein (that humans have). The small protein involved is not commonly studied in aging reseach, yet. The gene was controlled via the GAL4/UAS Expression System (allows gene to be targeted to specific tissues and/or global expression).

He and his cohorts were not optimized, for either expression levels, or for target location of expression.

I am sorry he died today.

#4 Karomesis

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Posted 17 June 2005 - 03:25 AM

DNAmechanic, forgive my ignorance but does the methuselah flys genetic alterations have anything to do with the IGF-1 pathway? if not, what mechanisms do you propose resulted in the life extension? [glasses]

#5 Mark Hamalainen

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Posted 17 June 2005 - 05:19 AM

I assume you are talking about the methuselah strain generated by Seymour Benzer and my current supervisor Laurent Seroude? I've attached the paper if you'd like more details prometheus.

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1998___Drosophila_mutant_methuselah.pdf 41.3KB 85 downloads

#6

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Posted 17 June 2005 - 06:17 AM

Thank's for the paper Osiris. Aha.. the mth gene which encodes a G-protein coupled receptor - and homozygous inheritance of the mutant mth extends lifespan. Is it known what the ligand for this receptor is yet?

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#7 Bruce Klein

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Posted 17 June 2005 - 06:23 AM

Interesting news. Sad to know he died, but for a noble cause.

It was a "he"? Do males live longer in fruit flies?

#8 dnamechanic

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Posted 17 June 2005 - 09:11 AM

To Karomesis,

Good question, I will try to answer in more detail soon.

No, the altered DNA is not related with the IGF-1 pathway.

Well, at least, not known to be directly related.

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To Osiris,

I recently thought this fly should have a name, beause it became clear that he would live a long life.

"Methuselah" seemed as good as any.

"Bob" just didn't seem appropriate

This work is unrelated to Seymour Benzer's work. The small protein expressed in these flies has not been commnly studied in aging research, yet.

I know some other labs are planning to work with this protein, or are they have already beginning some aging related work. Tho, to my knowledge, no effects on normal lifespan have yet been published.

When I initially started work generating these versions of this transgenic fly, I could find no references that this particular protein had been studied in aging research.

The embryo injection P-element transformation work was done was done in our lab, by myself and another grad student. This fly is a version 2.0. The first version used a different expression system, but gave hope that this might be a more robust version.

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To BJ,

'It was a "he"?"

Yes, Methuselah was a he.

For lifespan studies, our lab works mostly with male flies.

"Do males live longer in fruit flies?"

Female flies can live longer under certain circumstances.
For example, unmated "virgin" females live longer than females that have mated.

There are less variables involved when using male flies for aging studies.

#9 Da55id

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Posted 17 June 2005 - 03:34 PM

Will there be a published paper on these results? What did the fly die from if it's known.

#10 Mark Hamalainen

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Posted 17 June 2005 - 04:55 PM

This work is unrelated to Seymour Benzer's work. The small protein expressed in these flies has not been commnly studied in aging research, yet.

Ah sorry, methuselah is a common name I guess.

#11 dnamechanic

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Posted 17 June 2005 - 05:29 PM

Hi Osiris,

No problem

The name Methuselah has been almost synonymous with longevity.

"Methuselah" is getting more usage with the advent of the Methuselah Mouse Prize (MPrize).

The origin of the name, as you probably know, is in the Hebrew Bible.

Methuselah was the name of the oldest person recorded in the Hebrew scriptures.

Genesis 5:27

"And all the days of Methuselah were nine hundred sixty and nine years: and he died." KJV

#12 dnamechanic

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Posted 17 June 2005 - 06:40 PM

Will there be a published paper on these results?

I don’t know in what form the current data will be published.

I am documenting the current findings of these experiments (writing a paper).
It is likely that I can provide details in the near future, for those interested.

What did the fly die from if it's known

That is a thoughtful question.

I don’t know exactly what caused Methuselah fly’s death.

Flies, like humans in old age, get weaker in many ways.

One scientist, I know, has studied this problem. Some indications are that death is often caused by bacteria proliferation. It is plausible, in many cases, that the immune system becomes unable to cope, and eventually, bacteria wins the battle. If that is the scenario, then conceivably, the aging processes, causes the immune system to decline.

My observations are; most often, flies physically deteriorate with time and eventually cannot feed themselves. The decline often begins after they have lived about 1/3 of their maximum lifespan. Over a period of time they lose the ability to fly, then walking becomes difficult, then they cannot feed themselves.

Seems kinda familiar, huh?

#13 Da55id

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Posted 17 June 2005 - 06:58 PM

The use of the term Methuselah by the Methuselah Foundation is among other things, to implicitly remind those who are religious that it was/is ok with God for people to have significantly longer lifespans than that experienced today.

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Posted 17 June 2005 - 11:50 PM

This work is unrelated to Seymour Benzer's work. The small protein expressed in these flies has not been commnly studied in aging research, yet.

Can you disclose the name of the protein - if not what about the family it belongs to?

#15 John Schloendorn

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Posted 18 June 2005 - 03:25 AM

Is it just the light or do his legs and wings seem more pigmented than normal? Can it be lipofuscin?

#16 dnamechanic

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Posted 18 June 2005 - 12:20 PM

Can you disclose the name of the protein - if not what about the family it belongs to?

Prometheus, your question is a fair one.

I apologize to you.

When the fly story was posted, I realized there would be questions that I would prefer not to answer at this time.

I have seen very little information on maximum life span of Drosophila. This information was posted because it would probably be interesting to ImmInst members, such as you.

There may have been normal or other modified Drosophila that lived as long. If so, I am not aware.

Many researchers do not consider the lifespan of a single fly worth discussion (i.e. not statistically significant). Usually, attention is given to either the median or the mean (average) lifespan. This is useful because the numbers involved allow statistical validation.

It is unlikely that a fly such as this one would be mentioned in a peer-reviewed publication.

I think the maximum lifespan of any species is worth discussion. Probably, we can all agree that the lifespan of Jeane Louise Calment is a topic worthy of discussion.

It is good to have a number for maximum life span, even though it is a moving target.

Edited by dnamechanic, 18 June 2005 - 03:33 PM.

#17 dnamechanic

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Posted 18 June 2005 - 12:48 PM

Is it just the light or do his legs and wings seem more pigmented than normal? Can it be lipofuscin?

Very observative, John.

The light is not perfect.

The coloration varies greatly among the various strains of Drosophila.

The normal coloration patterns of Drospohila becomes less distinct as they age.

I had not thought of looking for lipofuscin.

The wings are somewhat transparent, and may be showing some of the background coloration. The background is actually a moist paper wiper.

The wings are a bit ragged on Methuselah, although they are pretty good shape for his age.

#18 manofsan

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Posted 18 June 2005 - 08:59 PM

Hmm, what colour is lipofuscin, anyway?

When you made the transgenic fly, did you only make one, or did you make others in order to see the consistency/variability of the life-extension effect? If there were others, how long did they live?

Gee, I hope none of these flies escape the lab, just so we don't end up with swarms of super-pests.

#19 dnamechanic

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Posted 19 June 2005 - 12:54 AM

Hmm, what colour is lipofuscin, anyway?

"Lipofuscin (age pigment) is a brown-yellow, electron-dense, autofluorescent material that accumulates progressively over time in lysosomes of postmitotic cells, such as neurons and cardiac myocytes."

http://www.ncbi.nlm....9&dopt=Citation

When you made the transgenic fly, did you only make one, or did you make others in order to see the consistency/variability of the life-extension effect?

The second part of your inquiry is the correct one.

Initially, several lines were developed.

Then, experimental lines were selected for the gene-of-interest being located in distinctly different positions in the chromosome, or located on different chromosomes.

The experimental lines were reduced further by selecting lines based on expression levels.

This culling process could go on, depending on whether or not one is lucky enough to have many transgenic lines to begin with.

If there were others, how long did they live?

Some groups lived longer than others. This one fly lived the longest.

Gee, I hope none of these flies escape the lab, just so we don't end up with swarms of super-pests.

Not to worry. These particular flies are far from super.

There are many published papers showing life extension in Drosophila.

#20 DukeNukem

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Posted 12 July 2005 - 09:03 PM

Was this fly still flying up to the day of his death (with good navigation skills)? Was there a period recently when he became noticeable more lethargic?

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#21 dnamechanic

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Posted 13 July 2005 - 12:11 AM

Was this fly still flying up to the day of his death (with good navigation skills)?

No, he probably had not been able to fly for some time, his wings were torn.
Ragged edges are visible in the photo where his wings overlap.

There were other flies with him up until about 115-125 days.
So, I never paid any attention to him until he became the last one or two living flies.

A couple of survivors of another cohort of these flies turned 125 days old today.
These guys are very quick and appear as active as a young flies. Although, their wings are torn.

As a result, they cannot fly well, but they do get airborne.

Torn wings are a hallmark of old age. Flies cannot restore torn wings.