Collaborations between Johns Hopkins and National Taiwan University researchers have successfully manipulated the life span of common, single-celled yeast organisms by figuring out how to remove and restore protein functions related to yeast aging.

A chemical variation of a “fuel-gauge” enzyme that senses energy in yeast acts like a life span clock: It is present in young organisms and progressively diminished as yeast cells age.

In a report in the September 16 edition of Cell, the scientists describe their identification of a new level of regulation of this age-related protein variant, showing that when they remove it, the organism’s life span is cut short and when they restore it, life span is dramatically extended.

In the case of yeast, the discovery reveals molecular components of an aging pathway that appears related to one that regulates longevity and lifespan in humans.

This control of longevity is independent of the type described previously in yeast which had to do with calorie restriction. We believe that for the first time, we have a biochemical route to youth and aging that has nothing to do with diet.”

The chemical variation, known as acetylation because it adds an acetyl group to an existing molecule, is a kind of “decoration” that goes on and off a protein — in this case, the protein Sip2 — much like an ornament can be put on and taken off a Christmas tree. Acetylation can profoundly change protein function in order to help an organism or system adapt quickly to its environment. Until now, acetylation had not been directly implicated in the aging pathway, so this is an all-new role and potential target for prevention or treatment strategies.

— Jef Boeke, Ph.D., professor of molecular biology, genetics and oncology, and director of the HiT Center and Technology Center for Networks and Pathways, Johns Hopkins University School of Medicine.

The team showed that acetylation of the protein Sip2 affected longevity defined in terms of how many times a yeast cell can divide, or “replicative life span.” The normal replicative lifespan in natural yeast is 25. In the yeast genetically modified by researchers to restore the chemical modification, life span extended to 38, an increase of about 50 percent.

The researchers were able to manipulate the yeast life span by mutating certain chemical residues to mimic the acetylated and deacetylated forms of the protein Sip2. They worked with live yeast in a dish, measuring and comparing the life spans of natural and genetically altered types by removing buds from the yeast every 90 minutes. The average lifespan in normal yeast is about 25 generations, which meant the researchers removed 25 newly budded cells from the mother yeast cell. As yeast cells age, each new generation takes longer to develop, so each round of the experiment lasted two to four weeks.

We performed anti-aging therapy on yeast. When we give back this protein acetylation, we rescued the life span shortening in old cells. Our next task is to prove that this phenomenon also happens in mammalian cells.”

Jin-Ying Lu, M.D., Ph.D., of National Taiwan University

The research was supported by the National Science Council, National Taiwan University Hospital, National Taiwan University, Liver Disease Prevention & Treatment Research Foundation of Taiwan, and the NIH Common Fund.

Authors on the paper, in addition to Boeke and Lu, are Yu-Yi Lin, Jin-Chuan Sheu, June-Tai Wu, Fang-Jen Lee, Min-I Lin, Fu-Tien Chian, Tong-Yuan Tai, Keh-Sung Tsai, and Lee-Ming Chuang, all of National Taiwan University; Yue Chen and Yinming Zhao, both of the University of Chicago; and Shelley L. Berger, Wistar Institute.

Contact info for the researchers:

• Boeke lab
• http://www.cell.com
• Media Contacts: Maryalice Yakutchik; 443-287-2251; myakutc1@jhmi.edu
• Audrey Huang; 410-614-5105; audrey@jhmi.edu
• Vanessa McMains; 410-502-9410; vmcmain1@jhmi.edu

It’s exciting news when lifespan is definitively extended by a drug therapy amenable to a supplementation regimen, particularly so in this case give that it’s an established drug.

Rapamycin, otherwise known as Sirolimus, is an immunosuppressant drug used to prevent rejection in organ transplantation; used especially following kidney transplant.

Here’s the abstract:

Rapamycin increases lifespan and inhibits spontaneous tumorigenesis in inbred female mice.

Anisimov VN, Zabezhinski MA, Popovich IG, Piskunova TS, Semenchenko
AV, Tyndyk ML, Yurova MN, Rosenfeld SV, Blagosklonny MV.

Department of Carcinogenesis and Oncogerontology; N.N.Petrov Research
Institute of Oncology; St. Petersburg, Russia.

The nutrient-sensing TO R (target of rapamycin) pathway is involved in cellular and organismal aging. Rapamycin, an inhibitor of TOR, extends lifespan in yeast, fruit flies and genetically heterogeneous mice. Here, we demonstrate that lifelong administration of rapamycin extends lifespan in female 129/Sv mice characterized by normal mean lifespan of 2 y.

Importantly, rapamycin was administrated intermittently (2 weeks per month) starting from the age of 2 mo. Rapamycin inhibited age-related weight gain, decreased aging rate, increased lifespan (especially in the last survivors) and delayed spontaneous cancer. 22.9% of rapamycin-treated mice survived the age of death of the last mouse in control group. Thus we demonstrated for the first time in normal inbred mice that lifespan can be extended by rapamycin.

This opens an avenue to develop optimal doses and schedules of rapamycin as an anti-aging modality.

PMID: 22107964 [PubMed - as supplied by publisher]

This result builds on some earlier experiments showing similar effect:

• Rapamycin fed late in life extends lifespan in genetically heterogeneous mice [PubMed; July 2009]
• Extension of chronological life span in yeast by decreased TOR pathway signaling [PubMed 2006]
• And, of related interest, rapamycin was found to rapidly reverse the mental deficits in a model of mouse autism

Those crazy guys at Boston Dynamics who brought you that scary and amazing petrol-powered BigDog now have a humanoid version: PETMAN

Nothing like vision of a headless terminator charging at one menacingly to engender hope for a bright, happy future!

ROCHESTER, Minn. — Researchers at Mayo Clinic have shown that eliminating cells that accumulate with age could prevent or delay the onset of age-related disorders and disabilities. The study, performed in mouse models, provides the first evidence that these “deadbeat” cells could contribute to aging and suggests a way to help people stay healthier as they age. The findings appear in the journal Nature along with an independent commentary on the discovery.

“By attacking these cells and what they produce, one day we may be able to break the link between aging mechanisms and predisposition to diseases like heart disease, stroke, cancers and dementia,” says co-author James Kirkland, M.D., Ph.D., head of Mayo’s Robert and Arlene Kogod Center on Aging and the Noaber Foundation Professor of Aging Research. “There is potential for a fundamental change in the way we provide treatment for chronic diseases in older people.”

Five decades ago, scientists discovered that cells undergo a limited number of divisions before they stop dividing. At that point the cells reach a state of limbo — called cellular senescence — where they neither die nor continue to multiply. They produce factors that damage adjacent cells and cause tissue inflammation. This alternative cell fate is believed to be a mechanism to prevent runaway cell growth and the spread of cancer. The immune system sweeps out these dysfunctional cells on a regular basis, but over time becomes less effective at “keeping house.”

As a result, senescent cells accumulate with age. Whether and how these cells cause age-related diseases and dysfunction has been a major open question in the field of aging. One reason the question has been so difficult to answer is that the numbers of senescent cells are quite limited and comprise at most only 10 to 15 percent of cells in an elderly individual.

“Our discovery demonstrates that in our body cells are accumulating that cause these age-related disorders and discomforts,” says senior author Jan van Deursen, Ph.D., a Mayo Clinic molecular biologist and the Vita Valley Professor of Cellular Senescence. “Therapeutic interventions to get rid of senescent cells or block their effects may represent an avenue to make us feel more vital, healthier, and allow us to stay independent for a much longer time.”

“Through their novel methodology, the research team found that deletion of senescent cells in genetically engineered mice led to improvement in at least some aspects of the physiology of these animals. So, with the caveat that the study involved a mouse model displaying accelerated aging, this paper provides important insights on aging at the cellular level,” says Felipe Sierra, Ph.D., Director of the Division of Aging Biology, National Institute on Aging, National Institutes of Health.

How They Did It

Dr. van Deursen and colleagues genetically engineered mice so their senescent cells harbored a molecule called caspase 8 that was only turned on in the presence of a drug that has no effect on normal cells. When the transgenic mice were exposed to this drug, caspase 8 was activated in the senescent cells, drilling holes in the cell membrane to specifically kill the senescent cells.

The researchers found that lifelong elimination of senescent cells delayed the onset of age-related disorders such as cataracts and muscle loss and weakness. Perhaps even more importantly, they showed that removing these cells later in life could slow the progression of already established age-related disorders.

The findings support a role of senescent cells in the aging process and indicate that chemicals secreted by these cells contribute to age-related tissue dysfunction and disease.

Other co-authors of the article are: Darren Baker, Ph.D., Tamar Tchkonia, Ph.D., Nathan LeBrasseur, Ph.D. and Bennett Childs, all of Mayo Clinic; and Tobias Wijshake and Bart van de Sluis, Ph.D., both of Groningen University, The Netherlands. The Ellison Medical Foundation, the Noaber Foundation, the Robert and Arlene Kogod Center on Aging, and the National Institutes of Health funded the study.

I recently became cognizant of the absence of my iTunes dashboard widget, which I had gradually come to use and eventually cherish, and I then discovered that the reason for its absence was that Apple has removed it outright from Mac OS X Lion!

Many a frustrated and futile minute I spent trying to locate the widget on Apple’s site, of course to no avail. Eventually, I resorted to retrieving it from an old Snow Leopard disc.

I am hereby providing the old widget (hopefully not to Apple’s easily-invoked annoyance) for anyone to freely download should they desire.

• Download: iTunes Widget

You need the following:

• For .ogg: Xiph QuickTime Component and place the file in /Library/QuickTime
• For .flac: Fluke and download and install the package

And then, importantly, you need to ‘get info’ on /Applications/iTunes.app and click the ‘Open in 32-bit mode’ checkbox, then restart QuickTime and iTunes.

Paul Allen wrote recently a very revealing article on his various ill-thought-out misgivings regarding Ray Kurzweil et al.’s predicted timetable for the so-called ‘Technological Singularity’.

The technological singularity is generally understood to occur on that day when, for the first time, a superhuman entity emerges from our collective efforts to create an electronic AI whose intelligence surpasses that of any human. With technology driven by minds whose workings are unfathomable to our present-day ordinary minds, our technological destinations and the rapidity of our ascent will accordingly be similarly, if not more so, unfathomable.

I wrote a response to Paul Allen’s article on reddit, which I will share here:

I feel like I write the same comment about every article that dismisses the possibility of a ‘singularity’ or suggests it will occur comfortably far into the future as to not concern us. The authors always make the same mistake, because they never really come to grips with true nature of this law of accelerating returns.

They seem only capable of extrapolating one aspect of technology at a time, without considering how these advances feed back into other areas. They don’t consider that the tools of discovery themselves are enhanced. The power of collaboration has improved phenomenally in recent times, but is still a relatively untapped resource.

Improved ways of working together will amplify the man-power devoted to technological advancement beyond present comprehension.

Today’s level of interconnection is unprecedented in history, and tomorrow’s will exceed today’s. As each human mind is freed to focus on a smaller piece of the puzzle, the collective mind is exponentially enhanced.

And, no new technological breakthroughs are even needed for this to occur. The current technological state of the art has only minimally propagated into society at this point.

Think about how world-changing this imminent breakthrough will be: software that translates the spoken word in real time. It sounds mundane, but when it reaches a level whereby people find it comfortable to use, suddenly the collaborative power of humanity will increase at least six fold as the non-English speaking world is suddenly able to participate fully in the primary technological and scientific discourse. Again, this would have an unknown effect on the rate of technological advance, but it would likely be much greater than simply 6x faster.

All these advances build on each other. It’s enormously difficult to predict the behavior of such a complex system, so Kurzweil’s approach of extrapolating general and long-term trends is the safest way to do it.

I actually think that the advancements will hit harder and faster than even the most optimistic futurists tend to admit to hoping for, but in the thick of it as we will be, it will only be on reflection that we realize how far we’ve come.

Nor do the authors really think about what the key phenomenon of singularity might really be, which to me is that event horizon, that cloak of unpredictability, of unknowability surrounding the singularity that confounds the imaginations of thoughtful science fiction writers all over the world.

In my opinion, the technological singularity includes an aspect of personal evolution.

The future has always been unknown, but I do wonder if my pre-Internet brain from 20 years ago could really fathom this current reality.

The entity in 2011 that is [me+Internet] is a markedly more capable being than I was before accumulating the knowledge from 20 years of organic and increasingly unimpeded learning. The delegation of more mundane mental tasks (such as memorization of facts) allows me to devote much more power to creative processes.

I feel like a totally different person to what I was, and I frankly can’t believe how impoverished my mental life was back then. Sure, I wasn’t lazy or incurious back then, but one was really in a state of learned educational helplessness in that if a question arose, there was no easy way for it to be answered, and it was likely to be forgotten by the time one was next in the library.

The point I was circling in that rant was that we might consider that we have already succeeded in creating our superhuman intelligences. Our present-day tools of instant information and of broad-scale collaboration have, in a way, already taken us past this milestone.

In my opinion, we will probably never see a discrete ‘AI that transcends the smartest human’, because before it is created we will inevitably see the development of neuro-electronic interfaces, and we’ll already be delegating much of our mental drudgery to our co-processing implants (or to ‘the cloud’ via a brain/network interface).

The comprehensive device-interconnectivity that will prevail at that point will make it difficult to really define the boundaries of an individual intelligence. Will we be able to say “This is the entity that surpasses all humans” when it’s likely that the processing tools utilized by this intelligence will be shared simultaneously by many humans and lesser AIs?

Even if, in typical fashion, IBM decides to create a disconnected ‘supercomputer AI’ for the sake of claiming that title, one wonders if it would be technologically feasible when its network-connected competition would have instant access to the sum total of human knowledge (as we all will).

So, I see more a gradual and harmonious convergence between human and artificial intelligence, rather than an abrupt change when suddenly our new robot overlords are revealed.

A few days later, Ray Kurzweil himself responded comprehensively to Paul Allen’s arguments. Worth the read.

If you’re tired of your laptop spinning up at 3:15 in the morning, as I am, what you need to do is reschedule these periodic tasks.

Edit these files to put in a more appropriate time:

/System/Library/LaunchDaemons/com.apple.periodic-daily.plist
/System/Library/LaunchDaemons/com.apple.periodic-monthly.plist
/System/Library/LaunchDaemons/com.apple.periodic-weekly.plist

Probably needs a restart to take effect.

This interesting Firefox plugin allows one to visualise the DOM as a stack of 3D objects using WebGL.

Worth a look!

http://hacks.mozilla.org/2011/07/tilt-visualize-your-web-page-in-3d/

After many minutes of futile tinkering and disappointment that it only supports a very standard color set, I finally arrived at an easy-to-read and attractive (in my opinion) theme.

Give it a go – not like there’s much choice out there.


# FlyingHigh.org CMus theme
set color_cmdline_bg=default
set color_cmdline_fg=red
set color_error=red
set color_info=lightyellow
set color_separator=black
set color_statusline_bg=black
set color_statusline_fg=white
set color_titleline_bg=black
set color_titleline_fg=lightyellow
set color_win_bg=default
set color_win_cur=red
set color_win_cur_sel_bg=red
set color_win_cur_sel_fg=white
set color_win_dir=blue
set color_win_fg=156
set color_win_inactive_cur_sel_bg=default
set color_win_inactive_cur_sel_fg=lightyellow
set color_win_inactive_sel_bg=default
set color_win_inactive_sel_fg=lightblue
set color_win_sel_bg=red
set color_win_sel_fg=white
set color_win_title_bg=black
set color_win_title_fg=lightyellow