Wired Science News for Your Neurons
New Longevity Drugs Poised to Tackle Diseases of Aging
By Brandon Keim
November 21, 2008
3:55 pm
Categories: Medicine
Cancer, diabetes, Alzheimer’s, Parkinson’s, heart disease: All have stubbornly resisted billions of dollars of research conducted by the world’s finest minds. But they all may finally be defied by a single new class of drugs, a virtual cure for the diseases of aging.
In labs across the country, researchers are developing several new drugs that target the cellular engines called mitochondria. The first, resveratrol, is already in clinical trials for diabetes. It could be on the market in four years and used off-label as an all-purpose longevity enhancer. Other drugs promise to be more potent and refined. They might even be cheap.
"It’s going to revolutionize western medicine," said Doug Wallace, a pioneer of mitochondrial medicine at the University of California atIrvine. "All the things that are common for an aging society, and nobody worried about when they died of infectious disease," he said, could be treated.
If the idea of a cure-all sounds fantastic, that’s because it is. History is littered with failed wonder drugs, elixirs of youth and miracle cures. But these new drugs have shown tremendous promise in mice. And though success in animals is far from a guarantee for humans, the research has gone from tantalizing curiosity to a possible foreshadowing of human health care in the 21st century.
As fewer people in the West die of infectious diseases, these new mitochondrial drugs could prevent a wide range of age-related illnesses, though they likely won’t extend the lifespans of healthy individuals.
Not long ago, the silver-bullet approach was disregarded, and it’s still far from achieving a consensus in the scientific community. But standard research approaches to cancer, dementia and heart disease have provided relatively small benefits, and evidence has continued to accumulate in favor of Wallace and like-minded researchers who advocate a mitochondrial theory of disease.
The new drugs work by stimulating enzymes that regulate the function of mitochondria. Hundreds of these structures are found in every cell in the body, ceaselessly converting glucose into usable energy. But over time, mitochondria degenerate. They lose strength and efficiency, releasing highly reactive oxygen molecules that bind easily with other molecules and wreak cellular havoc.
A growing number of scientists suspect that the breakdown of mitochondria is among the most important causes of cell-level changes that eventually cause the body’s tissues to degenerate with age. The damage accumulates gradually until hitting some critical mass of malfunction, at which point diseases arrive rapidly. That may be why so many diseases first occur during middle age, and become steadily more common afterwards.
Repair and prevent this damage, say proponents of the mitochondrial theory of disease, and those afflictions can be averted.
In the last year, mitochondrial malfunction was associated with heart disease, just as it’s also been associated with Alzheimer’s disease and diabetes. Researchers verified that the cellular changes produced by caloric restriction — a longevity-enhancing dietary intervention — are enjoyed by mice taking resveratrol, the first and best-known mitochondrial drug. Resveratrol, which also occurs naturally in red wine, didn’t extend the maximum lifespan of the mice, but it did protect them from the ravages of aging. Most recently, a next-generation longevity drug with the same molecular target as resveratrol allowed mice to gorge on high-fat food for four monthswithout gaining weight or developing diabetes.
Early-stage human trials of resveratrol for diabetes appear promising and have been expanded. Those trials are led by Sirtris Pharmaceuticals in Cambridge, Massachusetts , which claims to have several compounds in its pipeline that are stronger than resveratrol. The company was purchased last year by GlaxoSmithKline, signaling how seriously mitochondrial medicine is now taken by the pharmaceutical industry.According to Sirtris CEO Christoph Westphal, every major drug company is now researching mitochondrial targets.
For many sober-minded scientists, the question is no longer whether an intervention in age-related diseases will happen, but when. And they say it could be soon.
"Enough evidence has come out to suggest that, since we’ve now accomplished this successfully in other species, there’s reason to think we could do it in people," said Stephen Jay Olshansky, aUniversity of Illinois public health and aging expert, who recently co-authored a British Medical Journal article on the near future of anti-aging research.
Olshansky also co-authored an upcoming analysis of American demography in 2050 as part of a $3.9-million MacArthur Foundation research project on aging in America. The analysis assumes a multi-target breakthrough against the diseases of aging.
"We genuinely think it’s going to happen," he said. "We said that we not only believe it’s possible, but should be aggressively pursued as the new approach to health and disease prevention for this century."
But not everyone is so enthusiastic. Steve Austad, a University ofTexas gerontologist who warned two years ago against thinking of mice "as small little furry humans with long tails," is still unconvinced and doesn’t think that mitochondria will be an easy drug target. University of Southern California gerontologist Valter Longo noted associations between mitochondria and health aren’t yet as firm as their proponents suggest.
"As far as aging itself and the major diseases of aging are concerned, such as cancer and Alzheimer’s, we really have no idea how important mitochondrial damage is to it. It’s not clear that major diseases are caused by mitochondrial damage, though that’s still a good bet for where to go," Longo said. He added that resveratrol does appear promising for obesity and diabetes.
There’s also the issue of side effects. Resveratrol has proven safe in animals and early clinical trials, but much more testing is required.As a cautionary, Longo offered the example of his own research on caloric restriction and genetic manipulation of IGF-1, a cell-growth-regulating gene. In simple organisms, it’s produced the most-dramatic life extension ever seen — yeast lived 10 times its normal lifespan — but a group of Ecuadorians who naturally have that mutation have severe growth deficits and other health problems.
Even Longo, however, thinks resveratrol will enjoy some success in the near future, and mitochondrial approaches are being steadily embraced within the medical research community, which has been largely frustrated in its disease-by-disease, gene-centered approach.
"The approach we’ve taken is to go one disease at a time," saidOlshansky. "We’ve created national institutes to go after all these major diseases, and every time we identify a new gene, or do something that lets us attack disease a little more efficiently than before, everyone jumps up and says we’ve succeeded and that’s wonderful."
Such research is important, said Olshansky, but not as promising as hitting diseases at a common root. And though he won’t yet commit to resveratrol as a wonder drug, he suspects that mitochondria-targeting drugs will provide a breakthrough. The most important question now, he said, is how much the drugs will cost.
Harvard gerontologist David Sinclair, who co-founded Sirtris Pharmaceuticals and first showed resveratrol’s effect on mice, says the drug will be inexpensive. Since the company is testing its own formulation as a diabetes drug, it will need to be priced at just a few dollars per dose, competitive with other diabetes treatments. People who use it off-label for other diseases would pay the same price.
But that’s still speculative, said Olshansky, and there’s no guarantee of resveratrol’s efficacy. To make sure of success, he said, there needs to be a massive public investment in research.
"We believe we know how much it will cost to generate an intervention that slows aging in people," he said. "It will cost about $3 billion. It could be developed in enough time to influence the health and longevity of baby boomers. And any intervention that helps them will help all subsequent generations."
This may seem far-fetched. The makers of resveratrol and other mitochondrial medicines are merely the latest scientists to promise easy and universal health in a bottle. But everything is unproven until it’s proved.
"Powered flight research was fruitless until it wasn’t," said Aubrey deGrey, founder of the longevity-research-sponsoring MethuselahFoundation. "The harder we try, the sooner we’ll succeed."
Video: A mouse taking resveratrol (right) runs twice as far as a control mouse in the laboratory of David Sinclair / a4m1510
See Also:
Hacking the Human Life Span
Searching for Fountain of Youth in a Pill
Who Owns the Fountain of Youth?
Anti-Aging Drugs Could Change the Nature of Death
Malfunctioning Mitochondria May Cause Heart Disease
Pharmaceutical Fountain of Youth Could Cost Pennies
Caloric Restriction Comes in a Pill
Next-Generation Longevity Drug Works Mouse Wonders
Phreaking
Phreaking is a slang term coined to describe the activity of a subculture of people who study, experiment with, or explore telecommunication systems, like equipment and systems connected to public telephone networks. The term "phreak" is derived from the words "phone" and "freak". It may also refer to the use of various audio frequencies to manipulate a phone system. "Phreak", "phreaker", or "phone phreak" are names used for and by individuals who participate in phreaking. Additionally, it is often associated with computer hacking. This is sometimes called the H/P culture (with H standing for Hacking and P standing for Phreaking). information on this site is for educational purposes only! Wyretap Network ©2007 - 2010
Disclaimer: The information on this site is for educational and entertainment purposes only. It is not intended to encourage or teach you to break the law, that's what TV is for, albeit in a very flawed manner. The owner(s) of this website will not be held liable for anything you choose to do with the information contained on this site. If you want to learn how to rape, murder, loot, and commit acts of terror on a monumental scale, well, you won't find it here. Instead, tune-in to your nightly news and take a lesson from your 'elected' 'leaders'.
Disclaimer: The information on this site is for educational and entertainment purposes only. It is not intended to encourage or teach you to break the law, that's what TV is for, albeit in a very flawed manner. The owner(s) of this website will not be held liable for anything you choose to do with the information contained on this site. If you want to learn how to rape, murder, loot, and commit acts of terror on a monumental scale, well, you won't find it here. Instead, tune-in to your nightly news and take a lesson from your 'elected' 'leaders'.
Social engineering techniques and terms
All social engineering techniques are based on specific attributes of human decision-making known as cognitive biases.[1] These biases, sometimes called "bugs in the human hardware," are exploited in various combinations to create attack techniques, some of which are listed here:
Pretexting
Pretexting is the act of creating and using an invented scenario (the pretext) to persuade a targeted victim to release information or perform an action and is typically done over the telephone. It is more than a simple lie as it most often involves some prior research or set up and the use of pieces of known information (e.g. for impersonation: date of birth, Social Security Number, last bill amount) to establish legitimacy in the mind of the target. [2]
This technique is often used to trick a business into disclosing customer information, and is used by private investigators to obtain telephone records, utility records, banking records and other information directly from junior company service representatives. The information can then be used to establish even greater legitimacy under tougher questioning with a manager (e.g., to make account changes, get specific balances, etc).
As most U.S. companies still authenticate a client by asking only for a Social Security Number, date of birth, or mother's maiden name, the method is effective in many situations and will likely continue to be a security problem in the future.
Pretexting can also be used to impersonate co-workers, police, bank, tax authorities, or insurance investigators — or any other individual who could have perceived authority or right-to-know in the mind of the targeted victim. The pretexter must simply prepare answers to questions that might be asked by the victim. In some cases all that is needed is a voice that sounds authoritative, an earnest tone, and an ability to think on one's feet.
Phishing
Main article: Phishing
Phishing is a technique of fraudulently obtaining private information. Typically, the phisher sends an e-mail that appears to come from a legitimate business—a bank, or credit card company—requesting "verification" of information and warning of some dire consequence if it is not provided. The e-mail usually contains a link to a fraudulent web page that seems legitimate—with company logos and content—and has a form requesting everything from a home address to an ATM card's PIN.
For example, 2003 saw the proliferation of a phishing scam in which users received e-mails supposedly from eBay claiming that the user’s account was about to be suspended unless a link provided was clicked to update a credit card (information that the genuine eBay already had). Because it is relatively simple to make a Web site resemble a legitimate organization's site by mimicking the HTML code, the scam counted on people being tricked into thinking they were being contacted by eBay and subsequently, were going to eBay’s site to update their account information. By spamming large groups of people, the “phisher” counted on the e-mail being read by a percentage of people who already had listed credit card numbers with eBay legitimately, who might respond.
IVR or phone phishing
This technique uses a rogue Interactive voice response (IVR) system to recreate a legitimate sounding copy of a bank or other institution's IVR system. The victim is prompted (typically via a phishing e-mail) to call in to the "bank" via a (ideally toll free) number provided in order to "verify" information. A typical system will reject log-ins continually, ensuring the victim enters PINs or passwords multiple times, often disclosing several different passwords. More advanced systems transfer the victim to the attacker posing as a customer service agent for further questioning.
One could even record the typical commands ("Press one to change your password, press two to speak to customer service" ...) and play back the direction manually in real time, giving the appearance of being an IVR without the expense.
The technical name for phone phishing, is vishing.
Baiting
Baiting is like the real-world Trojan Horse that uses physical media and relies on the curiosity or greed of the victim.[3]
In this attack, the attacker leaves a malware infected floppy disk, CD ROM, or USB flash drive in a location sure to be found (bathroom, elevator, sidewalk, parking lot), gives it a legitimate looking and curiosity-piquing label, and simply waits for the victim to use the device.
For example, an attacker might create a disk featuring a corporate logo, readily available off the target's web site, and write "Executive Salary Summary Q2 2009" on the front. The attacker would then leave the disk on the floor of an elevator or somewhere in the lobby of the targeted company. An unknowing employee might find it and subsequently insert the disk into a computer to satisfy their curiosity, or a good samaritan might find it and turn it in to the company.
In either case as a consequence of merely inserting the disk into a computer to see the contents, the user would unknowingly install malware on it, likely giving an attacker unfettered access to the victim's PC and perhaps, the targeted company's internal computer network.
Unless computer controls block the infection, PCs set to "auto-run" inserted media may be compromised as soon as a rogue disk is inserted.
Quid pro quo
Quid pro quo means something for something:
An attacker calls random numbers at a company claiming to be calling back from technical support. Eventually they will hit someone with a legitimate problem, grateful that someone is calling back to help them. The attacker will "help" solve the problem and in the process have the user type commands that give the attacker access or launch malware.
In a 2003 information security survey, 90% of office workers gave researchers what they claimed was their password in answer to a survey question in exchange for a cheap pen.[4] Similar surveys in later years obtained similar results using chocolates and other cheap lures, although they made no attempt to validate the passwords.[5]
Other types
Common confidence tricksters or fraudsters also could be considered "social engineers" in the wider sense, in that they deliberately deceive and manipulate people, exploiting human weaknesses to obtain personal benefit. They may, for example, use social engineering techniques as part of an IT fraud.
The latest type of social engineering techniques include spoofing or hacking IDs of people having popular e-mail IDs such as Yahoo!, GMail, Hotmail, etc. Among the many motivations for deception are:
Phishing credit-card account numbers and their passwords.
Hacking private e-mails and chat histories, and manipulating them by using common editing techniques before using them to extort money and creating distrust among individuals.
Hacking websites of companies or organizations and destroying their reputation.
Pretexting
Pretexting is the act of creating and using an invented scenario (the pretext) to persuade a targeted victim to release information or perform an action and is typically done over the telephone. It is more than a simple lie as it most often involves some prior research or set up and the use of pieces of known information (e.g. for impersonation: date of birth, Social Security Number, last bill amount) to establish legitimacy in the mind of the target. [2]
This technique is often used to trick a business into disclosing customer information, and is used by private investigators to obtain telephone records, utility records, banking records and other information directly from junior company service representatives. The information can then be used to establish even greater legitimacy under tougher questioning with a manager (e.g., to make account changes, get specific balances, etc).
As most U.S. companies still authenticate a client by asking only for a Social Security Number, date of birth, or mother's maiden name, the method is effective in many situations and will likely continue to be a security problem in the future.
Pretexting can also be used to impersonate co-workers, police, bank, tax authorities, or insurance investigators — or any other individual who could have perceived authority or right-to-know in the mind of the targeted victim. The pretexter must simply prepare answers to questions that might be asked by the victim. In some cases all that is needed is a voice that sounds authoritative, an earnest tone, and an ability to think on one's feet.
Phishing
Main article: Phishing
Phishing is a technique of fraudulently obtaining private information. Typically, the phisher sends an e-mail that appears to come from a legitimate business—a bank, or credit card company—requesting "verification" of information and warning of some dire consequence if it is not provided. The e-mail usually contains a link to a fraudulent web page that seems legitimate—with company logos and content—and has a form requesting everything from a home address to an ATM card's PIN.
For example, 2003 saw the proliferation of a phishing scam in which users received e-mails supposedly from eBay claiming that the user’s account was about to be suspended unless a link provided was clicked to update a credit card (information that the genuine eBay already had). Because it is relatively simple to make a Web site resemble a legitimate organization's site by mimicking the HTML code, the scam counted on people being tricked into thinking they were being contacted by eBay and subsequently, were going to eBay’s site to update their account information. By spamming large groups of people, the “phisher” counted on the e-mail being read by a percentage of people who already had listed credit card numbers with eBay legitimately, who might respond.
IVR or phone phishing
This technique uses a rogue Interactive voice response (IVR) system to recreate a legitimate sounding copy of a bank or other institution's IVR system. The victim is prompted (typically via a phishing e-mail) to call in to the "bank" via a (ideally toll free) number provided in order to "verify" information. A typical system will reject log-ins continually, ensuring the victim enters PINs or passwords multiple times, often disclosing several different passwords. More advanced systems transfer the victim to the attacker posing as a customer service agent for further questioning.
One could even record the typical commands ("Press one to change your password, press two to speak to customer service" ...) and play back the direction manually in real time, giving the appearance of being an IVR without the expense.
The technical name for phone phishing, is vishing.
Baiting
Baiting is like the real-world Trojan Horse that uses physical media and relies on the curiosity or greed of the victim.[3]
In this attack, the attacker leaves a malware infected floppy disk, CD ROM, or USB flash drive in a location sure to be found (bathroom, elevator, sidewalk, parking lot), gives it a legitimate looking and curiosity-piquing label, and simply waits for the victim to use the device.
For example, an attacker might create a disk featuring a corporate logo, readily available off the target's web site, and write "Executive Salary Summary Q2 2009" on the front. The attacker would then leave the disk on the floor of an elevator or somewhere in the lobby of the targeted company. An unknowing employee might find it and subsequently insert the disk into a computer to satisfy their curiosity, or a good samaritan might find it and turn it in to the company.
In either case as a consequence of merely inserting the disk into a computer to see the contents, the user would unknowingly install malware on it, likely giving an attacker unfettered access to the victim's PC and perhaps, the targeted company's internal computer network.
Unless computer controls block the infection, PCs set to "auto-run" inserted media may be compromised as soon as a rogue disk is inserted.
Quid pro quo
Quid pro quo means something for something:
An attacker calls random numbers at a company claiming to be calling back from technical support. Eventually they will hit someone with a legitimate problem, grateful that someone is calling back to help them. The attacker will "help" solve the problem and in the process have the user type commands that give the attacker access or launch malware.
In a 2003 information security survey, 90% of office workers gave researchers what they claimed was their password in answer to a survey question in exchange for a cheap pen.[4] Similar surveys in later years obtained similar results using chocolates and other cheap lures, although they made no attempt to validate the passwords.[5]
Other types
Common confidence tricksters or fraudsters also could be considered "social engineers" in the wider sense, in that they deliberately deceive and manipulate people, exploiting human weaknesses to obtain personal benefit. They may, for example, use social engineering techniques as part of an IT fraud.
The latest type of social engineering techniques include spoofing or hacking IDs of people having popular e-mail IDs such as Yahoo!, GMail, Hotmail, etc. Among the many motivations for deception are:
Phishing credit-card account numbers and their passwords.
Hacking private e-mails and chat histories, and manipulating them by using common editing techniques before using them to extort money and creating distrust among individuals.
Hacking websites of companies or organizations and destroying their reputation.
The Real ID Coming Soon!!!
Friday, August 7, 2009
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