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Undoing Aging with Molecular and Cellular Damage Repair
Since the dawn of medicine, aging has been doctors’ foremost challenge.
by Aubrey D. N. J. de Grey November 28, 2017
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BBVA

Since the dawn of medicine, aging has been doctors’ foremost challenge. Three unsuccessful approaches to conquering it have failed: treating components of age-related ill health as curable diseases, extrapolating from differences between species in the rate of aging, and emulating the life extension that famine elicits in short-lived species. SENS Research Foundation is spearheading the fourth age of anti-aging research: the repair of age-related damage, that is, rejuvenation biotechnology.

The Strategies for Engineered Negligible Senescence (SENS) approach was first proposed in 2002. “Senescence,” here, refers to the actuarial phenomenon—the trend that individuals within a population suffer from an increasing morbidity and mortality rate in (typically exponential) relation to their chronological age. “Negligible” is used in a statistical sense: we consider a level of senescence negligible if no age-related contribution to mortality is statistically demonstrable within a population, given the “background noise” of age-independent mortality (such as unfortunate encounters with motor vehicles). Finally, by “Engineered,” we indicate that this state is achieved by the deliberate application of biomedical therapies, and is not the normal situation. The goal of SENSE is thus unambiguously defined; we seek methods to convert a population experiencing a non-negligible level of senescence into one experiencing a negligible level.

To see how the goal of negligible senescence could be “engineered,” it is useful to consider a situation in which human ingenuity and perseverance has already achieved an analogous result. Motor vehicles experience a process of wear-and-tear essentially similar to organismal aging; the paint flakes, windowpanes chip, rust infiltrates the pipework, and so forth. Nonetheless, as vintage car owners will attest, it is entirely possible to keep one functional for an essentially indefinite period. Critically, this is achieved not by preventing the wear but by repairing the damage that does occur at a rate sufficient to ensure that the function of the machine is never irretrievably compromised.

Of course, the analogy is inexact; human bodies are far more complex than cars but a closer look at precisely how growing older leads to debility reveals that our ignorance need not be showstopping.

Aging can be characterized as a three-stage process. In the first stage, metabolic processes essential to life produce toxins. Secondly, a small amount of the damage caused by these toxins cannot be removed by the body’s endogenous repair systems, and consequently accumulates over time. In the third stage, the accumulation of damage drives age-related pathology.

Undoing Aging with Molecular and Cellular Damage Repair
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This model—metabolism causes damage causes pathology—allows us to clarify the requirements for successful intervention in aging. Unlike the dynamic processes of metabolism and pathology, accumulated damage represents a relatively stationary target. That is to say, it may not be clear whether a given type of damage is pathological (on balance), but its absence from healthy twenty-year-olds indicates that it is not required for healthy life. Conversely it is clear that the total ensemble of types of damage is pathological, since fifty-year-olds have considerably less time to live than twenty-year-olds, and the only static difference between the two groups is the amount of accumulated damage present.

Accepting the implications of this model leads us to the SENS approach; by identifying and repairing all of the damage accumulated during aging, we can restore the body to a youthful state. Consequently, its dynamic metabolic processes will revert to their own norms, and the risk of mortality will be no higher than in any other equivalently “youthful” individual—whether they have actually lived for twenty years or 120. Furthermore—so long as our inventory of damage classes is sufficiently comprehensive—we can repeat this effort on a regular basis, and thus remain indefinitely below the threshold of pathology. Crucially, we can do this without a comprehensive understanding of the complex metabolic processes giving rise to damage, nor of those leading from damage to pathology. We need only an inventory of the types of damage which exist, which can be obtained directly by comparison of older and younger individuals. And, fortunately, it seems that all aging-related damage known to accumulate in the human body can be classified into just seven clearly defined categories: cell loss, cell death-resistance, cell over-proliferation, intracellular and extracellular “junk”, tissue stiffening and mitochondrial defects.

SENS is a hugely radical departure from prior themes of biomedical gerontology, involving the bona fide reversal of aging rather than its mere retardation. By virtue of a painstaking process of mutual education between the fields of biogerontology and regenerative medicine, it has now risen to the status of an acknowledged viable option for the eventual medical control of aging and its credibility will continue to rise as the underlying technology of regenerative medicine progresses.

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Is the U.S. Hypocritical to Criticize Russian Election Meddling?

What “Whataboutism” Gets Wrong

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The U.S. response to Russian meddling in the 2016 election has been extraordinarily weak. Not only that, it has been accompanied by an attitude of “whataboutism” on the part of some Americans—the relativistic view that the United States has little ground to complain about Russia’s actions given its own history of meddling in other countries’ political campaigns and elections. It is certainly essential to be honest and realistic about the considerable record of past U.S. electoral meddling, and the contrast between Russia and the United States in this domain is certainly not black and white. Yet neither is it one of indistinguishable shades of gray. The United States is simply not engaging in electoral meddling in a manner comparable to Russia’s approach.

THE PAST IS NOT THE PRESENT

Two key flaws underlie relativist accounts. First, such a position fails to distinguish adequately between the pattern of U.S. interventionism during the Cold War, on the one hand, and U.S. activity since the end of the Cold War on the other. During the former period, the United States did indeed illegitimately intervene in numerous foreign elections, trying to tilt outcomes in favor of candidates the United States preferred and in a smaller number of cases laboring to oust legitimately elected leaders Washington saw as hostile to its security and economic interests. The record is long and dark, marked by some especially well-known cases in Guatemala and Iran in the early 1950s and in Chile and Nicaragua in the 1970s and 1980s.

Since the end of the Cold War, however, such interventionism has decreased significantly because U.S. policymakers no longer view the world as enmeshed in a global ideological struggle in which every country, no matter how small, is a critical piece on a larger strategic chessboard. Washington has thus become much less concerned about the outcomes of most foreign elections and much less engaged in trying to tilt them in any particular direction.

Of course, one can identify a few cases over the past 25 years when the United States has tried to manipulate foreign elections with the aim of getting its preferred candidate into power. When Russian President Boris Yeltsin faced reelection in 1996, the Clinton administration mobilized some economic relief to Yeltsin, to try to help him win. In the Palestinian elections of 2006, the George W. Bush administration employed U.S. economic assistance to try to bolster Fatah in its contest with Hamas (with predictably counterproductive results). In the lead up to the 2005 Iraqi elections, the Bush administration formulated a plan to funnel covert funds to favored Iraqi candidates and parties but reportedly backed away from the plan after Congress objected. In 2009, according to former Defense Secretary Robert Gates’ memoir, the United States worked behind the scenes prior to the Afghanistan elections to push President Hamid Karzai aside and keep him from winning.

There have no doubt been other cases, known only to those with access to classified information. Yet on the whole, U.S. electoral meddling has decreased significantly since the Cold War years. This is true because of the change in U.S. interests and because of an evolution of norms in many parts of the U.S. policy establishment about the acceptability of such actions. The overall picture today is of a Russia actively expanding its covert electoral meddling in multiple regions as U.S. meddling continues to decline. Those convinced that Washington must still routinely use covert means to influence election outcomes all around the world should consider the available evidence: in the last few years the rising pattern of Russian efforts to manipulate the political life of countries in central Europe, western Europe, the Balkans, the United States, and Latin America has left many telltale fingerprints—it seems highly unlikely Washington could have carried out a similar pattern of activities and not leave behind at least some noticeable traces of them.

On the whole, U.S. electoral meddling has decreased significantly since the Cold War years.

WHAT ABOUT ALL THAT DEMOCRACY PROMOTION?

A second problematic element of the relativist position is the charge that U.S. efforts to promote democracy abroad—which make use of diplomatic leverage, democracy aid, and cooperation with pro-democratic multilateral organizations—are just another, more covert form of electoral meddling akin to what the Russians are doing. Russian President Vladimir Putin is a strong subscriber to this viewpoint, convinced that U.S. and other Western democracy programs in his country represent efforts to manipulate its domestic political life against him. Many Western observers—acutely aware of the long record of U.S. interventionism—have their suspicions as well.

U.S. pro-democracy diplomacy and assistance do indeed seek to shape the political direction of other countries. And they are carried out with a strong sense of self-interest, not out of unalloyed idealism. They are driven by the belief that democratic outcomes abroad will generally be favorable to U.S. security and economic interests by producing stable governments amenable to deeper partnerships thanks to shared political values. But unlike Russian electoral meddling, U.S. democracy promotion does not seek to exacerbate sociopolitical divisions, systematically spread lies, favor particular candidates, or undercut the technical integrity of elections. On the whole, it seeks to help citizens exercise their basic political and civil rights in electoral processes, enhance the technical integrity of such processes, and increase electoral transparency.

Skeptics reluctant to accept the idea that democracy diplomacy and assistance are not about manipulating elections should look at some recent cases—such as U.S. efforts to support Tunisia’s democratic evolution, to help Gambia resolve the blockage that followed its 2016 elections, to encourage the Hungarian government to respect media freedom and civic space, and to push the Myanmar military at the start of this decade to make room for at least some democratic political life in the country.

Skeptics should also note that although the U.S. organizations engaged in democracy work are mostly funded by the U.S. government itself, they are regularly at odds with the preferences of U.S. diplomats, who often hold on to relationships with friendly autocrats, as they are wary of the strategic value of democratic change. In the mid-1990s, this was true in Indonesia under former President Suharto and in Kazakhstan under President Nursultan Nazarbayev. And in the first decade of this century, the same occurred in Egypt under former President Hosni Mubarak and in Azerbaijan under the Aliyev family. Skeptics should also bear in mind that in most cases where the United States is engaged in promoting democracy abroad, it is working alongside and sometimes in active partnership with other democracies not known for geopolitical interventionism, such as Denmark, the Netherlands, and Sweden.

GRAY AREAS

Although the overall case is strong for distinguishing U.S. democracy support abroad from the sort of political meddling that Russia is now making a habit of, there are several difficult issues that necessarily complicate the comparison. First, in a small but important number of cases, the United States does assist one side of a contested electoral campaign against the other. This occurs when a strongman leader of doubtful democratic fidelity is trying to legitimate himself and perpetuate his rule through elections. In various such cases, as with Chilean President Augusto Pinochet’s plebiscite in 1988, Slobodan Milosevic’s reelection campaign in 2000, and various Belarusian elections in the 2000s, the United States and a number of other Western actors offered assistance both to the opposition political forces challenging the strongman and to civic groups that were mobilizing get-out-the-vote campaigns. From the Western point of view, such actions are not interfering in a free and fair election but rather trying to help level the playing field in an election that is stacked unfairly against the challengers. From the point of view of the power holders, of course, the United States and its allies are trying to shape the outcome of the election in a partisan fashion.

Second, although U.S. and other Western assistance to civil society aims to aid civic actors in their advocacy of rights and democracy—not to take sides in partisan political struggles and campaigns—the line between political society and civil society is often blurry. What to Western providers are principled civic actors working to advance universally valid political and civil rights and democratic values such as transparency and accountability, are to local authorities political animals cloaked in civic garb challenging their hold on power. This is especially true in partially or fully closed political environments such as exist in Cambodia and Venezuela, where regimes have choked off the opposition and demonstrated an ability to undermine elections.

Third, despite the fact that most U.S. and Western democracy promotion is carried out in a transparent manner, some aid providers are becoming less transparent in their assistance in order to protect their recipients from being harassed or persecuted. As a result, a growing number of regimes have accused the West of engaging in clandestine political meddling. This scenario creates a vicious cycle in which undemocratic regimes charge democracy promoters of secretive meddling and persecute those they work with, thus driving such organizations to adopt less transparent methods. This in turn further reinforces the perception of secretive meddling. U.S. democracy assistance directed at Iran, for example, has become much less transparent over the past ten years as crackdowns by the Iranian government on recipients of foreign assistance have intensified.

Fourth, U.S. democracy policy is markedly inconsistent, even though U.S. efforts to promote democracy in other countries are generally driven by genuine pro-democracy motives. The U.S. government makes more funds available for democracy programs in countries that the United States views as strategic enemies, such as Iran and Cuba, than it does in nondemocratic countries the United States views as strategic partners, such as Saudi Arabia and Ethiopia. The inconsistency is not absolute. Washington does make some efforts to promote democracy and rights in states ruled by “friendly tyrants.” The Trump administration’s decision last year to withhold some U.S. assistance to Egypt as a means of expressing dissatisfaction with President Abdel Fattah el-Sisi’s antidemocratic policies is just one example. And the fact that one is inconsistent in applying the principle does not render meaningless the applications that are made. Nevertheless, the inconsistency hurts the larger case that democracy promotion has real roots in principle.

DIVERGENT PATHS

It is not yet clear what it will take for the United States to move forward in putting together an effective response to Russian electoral meddling, but dispensing with the argument that Washington has no moral standing for objecting to such actions is certainly one necessary step. The arguments over “whataboutism” merit some careful reflection and assessment given that the facts are not simple and not all the facts are available. The United States does have a past record of electoral meddling, particularly during the Cold War. Yet the trends of U.S. and Russian behavior are divergent, not convergent—with Russia on the negative side of the divide. And although the domain of U.S. democracy promotion is hardly free of flaws and serious past mistakes, it is not the dark twin of the illicit, covert election meddling that Russia seems intent on making one of its defining signatures abroad

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Cocktail Party At The Imperial Hotel, 1961

After World War I, the idea of the “working woman” became popular. Since 1929, it was more common to see women in a social atmosphere. With the help of liberation organizations, the idea of a “modern woman” began to rise, and soon the “drinking woman” could be seen in business settings.[1] Companies increasingly hosted cocktail parties to have an entertaining environment for employees and customers to mingle. These parties usually began after 5:00 P.M.[2] Since guests are expected to walk around and meet people, clothes made for these occasions are often functional and comfortable. A cocktail dress could be worn to any event in the late afternoon as long as the accessories matched the time of day. This practical and fashionable garment became a popular uniform for progressive elite women in the 1920s.[3]

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History[edit]

American Cocktail Dress 1950s

During the 1920s, French couture’s clientele consisted mainly of American department stores that reproduced French designs and promoted French designers. This caused French designers to create dresses to appeal to American buyers.[1]Since cocktail parties originated in the United States, French designers created their own version of a cocktail dress. However, unlike the strict, professional cuts of American-styled dresses, the French designed much looser and free flowing beach pajamas,[3][4] consisting of a silk top and palazzo pants, usually paired with a mid-calf-length wrap jacket or sheath.[3][4]These clothes are usually worn for more exclusive and intimate gatherings. The French style valued simplicity and elegance in their designs while American style valued functionality and efficiency. American clients wanted a single dress that could be modified to fit several times of the day with the use of accessories.[5] The fabric of the dress and whether it was worn with a cocktail hat differentiated a day dress from a cocktail dress.[3] By the mid-1920s, the hemlines of the dresses were right below the knee rather than ankle-length, which was more common for evening gowns.[3]

Italian Cocktail dress, 1960

The Great Depression[edit]

To take account for the economic crisis, designers such as Muriel King emphasized the importance of accessories by designing simple dresses,[3] which also helped the market for jewelry, hats, gloves, and sheaths. However, after the Wall Street Crash of 1929, private cocktail parties became more popular than corporate gatherings as luxurious lifestyles were no longer seen as fashionable. These elite gatherings helped the rise of day-to-evening fashion.[3]

Post-World War II[edit]

After World War IIDior came out with the “New Look”, which consisted of a tight waistline, long hemlines, and fuller skirts. This style flattered the women silhouette and created a romantic aura around the aesthetic.[3] Since cocktail parties were so popular, American designers such as Anne Fogarty began to create cocktail dresses that revolved around the “New Look” using less expensive fabrics.[3] French designers, such as Dior and Jacques Fath, saw the high market for cocktail dresses and began to design dresses for American department stores.[3]

Trend spreading[edit]

With the increasing feasibility and popularity of air travel, French cocktail dresses became popular globally.[3] As French women traveled to wealthy resort cities, the designs of their cocktail dresses spread among the American elite. While French couture relied on travel and American department stores, American designers relied on fashion magazines, such as Vogue and Vanity Fair, and the need to dress semi-formally for cocktail hour.[3]

In 1948, Christian Dior labeled this business-casual dress with the term “cocktail dress”. This allowed department store to advertise specifically “cocktail” garments and accessories, increasing the growth of fashion stores.[6] The craze for cocktail culture drove sales in cocktail merchandise as well, such as cocktail and martini-printed fabrics.[3]

Jody Watley in a 1950s black sequined cocktail dress in 1990

Dress style[edit]

The American cocktail dress could be anything from a “little black dress” to a floral-printed dress or a plain, short evening gown, as long as it was worn with accessories.[7]These might be earrings, pearl necklacesbracelets, or brooches (stylish in the 1950s).[7] However, it was mostcommon to wear costume jewelry.[3] Although they were inexpensive, wearing large amounts was seen as daring and luxurious, especially when wearing a modest dress.[3] In addition, the jewelry would be worn along with hats: velvetlace, or horsehair; little turbans or close-fitting caps of brocadetaffeta, or satin.[7] Gloves needed to be fashionably up-to-date and could be any length, material, or color.[7] Shoes were usually high heels, but evening satin sandals were also common and could be dyed to match the color of the dress.[7]

Dress code[edit]

As cocktail parties became more high-end, the attire became subject to stricter guidelines, which allowed people to easily differentiate between the different identities at the party, the organizer, hostess, and wife.[3]There were strict rules of etiquette as women needed to wear gloves, hostesses were not allowed to wear accessories, and guests were required to wear cocktail hats, but never indoors