The 2045 Initiative is a fairly young but comparatively well-backed effort to generate more support for and technological progress towards non-biological means of human life extension: artificial bodies, and ultimately artificial brains, built to be far more resilient and maintainable than our present evolved equipment. There is some debate over whether this is an efficient course in comparison to medical research, but that end of the futurist community already primarily interested in strong artificial intelligence seem to like where this is going.

There is a lot of fascinating groundwork in reverse-engineering the human brain presently under way, and it's clear that neuroscience is going to become an interesting place to be over the next few decades. However, I remain unconvinced that any of this is going to help us get over the initial hurdles to extending human longevity, meaning the frailty and short life span of the human body and physical structures that support the mind, soon enough to matter. Artificial intelligence and human minds running on machinery will certainly come to pass, and I will be surprised if the latter fails to happen in the laboratory prior to 2050 given the pace at which available processing power is growing. However, and this is important, over that time scale most of us doing the writing and the reading here and now are dead without some means of medical treatment for aging. This is one of the reasons why I pay less attention to neuroscience and mind-machine interface development than I do to repair biotechnologies for the causes of aging.

The Global Futures 2045 conference series is a part of the 2045 Initiative advocacy, and the most recent event took place a couple of months ago. I noted some of the media reports at the time. A two part report published earlier this month is quoted below and focuses more on the presentations than did past articles in the popular press, which I think is a good thing.

The world according to Itskov: Futurists convene at GF2045 (Part 1)

The development of brain-computer interfaces (BCIs) to allow paralyzed individuals to control various external prosthetic devices, such as a remote robotic arm, was another key topic at GF2045. A very recent example of the BCI research Carmena and Maharbiz discussed is Neural Dust: An Ultrasonic, Low Power Solution for Chronic Brain-Machine Interfaces. The theoretical pre-print paper proposes neural dust - thousands of ultra-miniaturized, free-floating, independent sensor nodes that detect and report local extracellular electrophysiological data - with neural dust power and communication links established through a subcranial interrogator. With the purpose being to enable "massive scaling in the number of neural recordings from the brain while providing a path towards truly chronic BMI," the researchers' goal is "an implantable neural interface system that remains viable for a lifetime."

In Making Minds Morally: the Research Ethics of Brain Emulation, Dr. Anders Sandberg - a Computational Neuroscientist, and James Martin Research Fellow at the Future of Humanity Institute at Oxford University, and Research Associate at the Oxford Neuroethics Center - addressed the social and ethical impact of cognitive enhancement and whole brain emulation. "We want to get to the future," Sandberg said in his talk, "but that implies that the future had better be a good place. Otherwise, there wouldn't be a point in getting there - but that would mean in turn that the methods we're going to use to get to the future had better be good as well."

The world according to Itskov: Futurists convene at GF2045 (Part 2)

Dr. Theodore Berger gave the most groundbreaking presentation of the Congress - one that also received a standing ovation. In Engineering Memories: A Cognitive Neural Prosthesis for Restoring and Enhancing Memory Function, Berger discussed his extraordinary research in the development of biomimetic models of hippocampus to serve as neural prostheses for restoring and enhancing memory and other cognitive functions. Berger and his colleagues have successfully replaced the hippocampus - a component of the cortex found in humans and other vertebrates that transforms short-term memory into long-term memory - with a biomimetic VLSI (Very Large-Scale Integrated circuit) device programmed with the mathematical transformations performed by the biological hippocampus.

Dr. Randal Koene, neuroscientist, neuroengineer and science director of the 2045 Initiative, has been focusing on the functional reconstruction of neural tissue since 1994. In his Whole Brain Emulation: Reverse Engineering A Mind presentation and soon-to-be published book with the same title, Koene describes the process of progressing from our current condition to a possible substrate-independent mind achieved by whole brain emulation and cites a wide range of research, including the work of fellow GF2045 presenters.

Source:
https://www.fightaging.org/archives/2013/08/a-two-part-report-on-global-futures-2045.php

The immune system declines greatly with aging, and poor immune response is an important component of age-related frailty: old people become vulnerable to infections that the young can shrug off with ease. So we might expect to see that long-lived people have better immune systems, and that whatever underlying mechanisms cause that difference are to some degree inherited.

People may reach the upper limits of the human life span at least partly because they have maintained more appropriate immune function, avoiding changes to immunity termed "immunosenescence." Exceptionally long-lived people may be enriched for genes that contribute to their longevity, some of which may bear on immune function. Centenarian offspring would be expected to inherit some of these, which might be reflected in their resistance to immunosenescence, and contribute to their potential longevity. We have tested this hypothesis by comparing centenarian offspring with age-matched controls. We report differences in the numbers and proportions of both CD4+ and CD8+ early- and late-differentiated T cells, as well as potentially senescent CD8+ T cells, suggesting that the adaptive T-cell arm of the immune system is more "youthful" in centenarian offspring than controls. This might reflect a superior ability to mount effective responses against newly encountered antigens and thus contribute to better protection against infection and to greater longevity.

The goal of future medicine is to make inherited differences of this nature irrelevant. There are a number of promising approaches that may remove much of the age-related decline of immune function: regrow the atrophied thymus, where immune cells are cultured; create new immune cells in the clinic and infuse them regularly into older people; destroy the population of over-specialized memory cells that exist in the elderly, thus freeing up space for effective immune cells that can combat new threats.

Link: http://www.ncbi.nlm.nih.gov/pubmed/23974207

Source:
https://www.fightaging.org/archives/2013/08/children-of-long-lived-parents-have-better-immune-systems.php

Aging is damage: it is the accumulation of broken and obstructed protein machinery and nanoscale structures inside and around our cells. Living beings come with many varied repair systems, so the processes by which damage grows and eventually overwhelms those repair systems is far from straightforward. In that sense aging isn't like the wearing of stone by the weather, or the failure of a non-repairing mechanical system like a car - but it's still all about damage. At the highest level the same mathematical models of damage and component loss that work just fine as aids to understanding failure in complex non-repairing systems like electronics also work just fine for aging.

Every so often a research group feels the need to publicize work in which they damage mice or other laboratory species in ways that cause them to live shorter lives. There are many very subtle ways to alter genes, such as those involved in DNA repair, that produce what is arguably accelerated aging. (Though not everyone thinks that these forms of life span reduction are in fact accelerated aging, but that's a debate for another time and place). The point here is that I think you have to beware of taking it at face value that these research results are relevant to normal aging, or relevant to extending healthy life. You can damage mice with a hammer if you so choose, and it will certainly shorten their life spans, but examining the results won't tell you anything about aging. Similarly, it's the case that near all of the possible ways of interfering in mouse biology via genes and metabolic operation in order to reduce life span are just as irrelevant.

Here is an example of this sort of thing: researchers are producing mice with additional damage in their mitochondria, a component of cellular biology known to be important in all sorts of metabolic processes, and considered to be important in aging, and showing that these mice don't live as long. I don't think that the authors can show that they've proved much of relevance to aging with this study as constructed, however, for the reasons noted above.

Mutations of mitochondrial DNA can hasten offspring's ageing process

In ageing research, mitochondria have been scrutinized by researchers for a long time already. The mitochondria in a cell contain thousand of copies of a circular DNA genome. These encode, for instance, proteins that are important for the enzymes of the respiratory chain. Whereas the DNA within the nucleus comes from both parents, the mitochondrial DNA (mtDNA) only includes maternal genes, as mitochondria are transmitted to offspring via the oocyte and not via sperm cells. As the numerous DNA molecules within a cell's mitochondria mutate independently from each other, normal and damaged mtDNA molecules are passed to the next generation.

To examine which effects mtDNA damage exerts on offspring, researchers used a mouse model. Mice that inherited mutations of mtDNA from their mother not only died quicker compared to those without inherited defects, but also showed premature ageing effects like reduced body mass or a decrease in male's fertility. Moreover, these rodents were prone to heart muscle disease.

As the researchers discovered, mutations of mtDNA not only can accelerate ageing but also impair development: In mice that, in addition to their inherited defects, accumulated mutations of mtDNA during their lifetime, researchers found disturbances of brain development. They conclude that defects of mtDNA that are inherited and those that are acquired later in life add up and finally reach a critical number.

To show relevance, you really need to demonstrate life extension - meaning repair mechanisms for mitochondrial DNA rather than damage mechanisms should be the focus. To shorten life spans through various forms of damage is unlikely to provide anything more than hints and inference when it comes to ways to extend life.

Source:
https://www.fightaging.org/archives/2013/08/damaging-the-biology-of-mice-to-make-them-age-more-rapidly-often-tells-us-little-of-use.php

The modern movements of transhumanism and support for longevity science have deep roots: you can find early expressions of the ideas of human enhancement and overcoming natural limits on our biology in a range of writings from past centuries. These ideas became more commonplace and more complex over time as the prospects for technology caught up with our desires:

Immanuel Kant (1724-1804) was an 18th century philosopher, one of the earliest philosophers belonging to the enlightenment tradition, and often considered the father of German Idealism. Kant is remembered today more for his moral philosophy than his contributions to metaphysics and epistemology (Rohlf 2010). His contributions to the field of life-extension, however, remain almost completely unexplored, despite the fact that certain claims made in his Theory of Ethics arguably qualify him as a historical antecedent of the contemporary social movement and academic discipline of life-extension.

Marquis du Condorcet (1743-1794), another historical antecedent the modern longevity movement, appears to have originated the "idea of progress" in the context of the enlightenment, which became an ideological cornerstone of the enlightenment tradition. In Sketch for a Historical Picture of the Progress of the Human Mind, Condorcet not only conceives of the idea of progress in perhaps the first form it would take within the enlightenment tradition, but also explicates its link to indefinite life-extension, which was not an existing movement or academic discipline at the time of his writing:

"Would it be absurd now to suppose that the improvement of the human race should be regarded as capable of unlimited progress? That a time will come when death would result only from extraordinary accidents or the more and more gradual wearing out of vitality, and that, finally, the duration of the average interval between birth and wearing out has itself no specific limit whatsoever? No doubt man will not become immortal, but cannot the span constantly increase between the moment he begins to live and the time when naturally, without illness or accident, he finds life a burden?"

It is this very notion of infinite progress towards endlessly-perfectible states, carried forward after Condorcet by Kant and other members of the enlightenment tradition, that also underlies Kant's own ties to the contemporary field of life-extension. Kant's claim, made in his Theory of Ethics, that to retain morality we must have comprehensively unending lives - that is, we must never, ever die - I will argue qualifies him as a historical antecedent of the contemporary life-extension movement.

Link: http://hplusmagazine.com/2013/08/21/immanuel-kant-morality-necessitates-immortality/

Source:
https://www.fightaging.org/archives/2013/08/a-look-back-at-some-of-the-roots-of-modern-thought-on-radical-life-extension.php

A conservative view of what lies ahead for Alzheimer's disease (AD) research sees incremental progress resulting from new and better investigative biotechnologies:

In the recently published work "The Biology of Alzheimer Disease" (2012), most of what is known about AD today is described in detail. The book culminates in a chapter called Alzheimer Disease in 2020, where the editors extol "the remarkable advances in unraveling the biological underpinnings of Alzheimer disease...during the last 25 years," and yet also recognize that "we have made only the smallest of dents in the development of truly disease modifying treatments." So what can we reasonably expect over the course of the next 7 years or so? Will we bang our heads against the wall of discovery, or will there be enormous breakthroughs in identification and treatment of AD?

Though a definitive diagnosis of AD is only possible upon postmortem histopathological examination of the brain, a thorough review of the book leads me to believe that the greatest progress currently being made is in developing assays to diagnose AD at earlier stages. It is now known that neuropathological changes associated with AD may begin decades before symptoms manifest. This, coupled with the uncertainty inherent in a clinical diagnosis of AD, has driven a search for diagnostic markers. Two particular approaches have shown the most promise: brain imaging and the identification of fluid biomarkers of AD.

The authors anticipate that advances in whole-genome and exome sequencing will lead to a better understanding of all of the genes that contribute to overall genetic risk of AD. Additionally, improved ability to sense and detect the proteins that aggregate in AD and to distinguish these different assembly forms and to correlate the various conformations with cellular, synaptic, and brain network dysfunction should be forthcoming in the next few years. Lastly, we will continue to improve our understanding of the cell biology of neurodegeneration as well as cell-cell interactions and inflammation, providing new insights into what is important and what is not in AD pathogenesis and how it differs across individuals, which will lead, in turn, to improved clinical trials and treatment strategies.

Link: http://www.alcor.org/magazine/2013/08/21/alzheimer-disease-in-2020/

Source:
https://www.fightaging.org/archives/2013/08/the-next-few-years-of-research-into-alzheimers-disease.php

Technologies derived from rapid prototyping and 3-D printing will likely play an important role in the future of tissue engineering, just as they are coming to do in many fields:

The field of tissue engineering has deployed several fabrication strategies aimed at bringing cells and structure together to generate tissue. Biomaterial scaffolding - which provides structural support and can be formed into biologically relevant shapes - has been combined with cells to generate hybrid 3-D structures for use as tissue surrogates in vitro and in vivo. Protocols have been developed that enable removal of living cells from native tissues, leaving only a natural scaffolding of extracellular matrix, which can then be re-seeded with cells to reconstruct or partially reconstruct 3-D tissues. Another approach to soft tissue reconstruction has been the development of cell-laden hydrogels, which are often cast into a specific shape and placed into a permissive environment in vitro or in vivo that allows maturation and establishment of tissue-specific characteristics. In recent years, with the advancement of 3-D printing technologies for the on-demand fabrication of complex polymer-based objects, efforts have been underway to adapt 3-D printing technologies and engineer bioprinting instruments that can leverage similar 3-D replication concepts and accommodate the incorporation of living cells.

Organovo's NovoGen MMX Bioprinter precisely dispenses "bio-ink" - tiny building blocks composed of living cells - generating tissues layer-by-layer according to user-defined designs. Built for flexibility, the bioprinter enables fabrication of tissues with a wide array of cellular compositions and geometries; side-by-side comparison of multiple tissue prototypes facilitates optimization and selection of specific designs geared toward a particular application. Working within the confines of an object library, bio-ink building blocks of various shapes, sizes and compositions are assembled into architectures that recapitulate the form of native tissue. Tubes, layered sheets and patterned structures have been bioprinted, yielding 3-D tissues that are free of biomaterial scaffolding and characterized by tissue-like microarchitecture, including the development of intercellular junctions and endothelial networks.

In the short-term, 3-D human tissues are being deployed in the laboratory setting as models of human physiology and pathology; cell-based assays are a mainstay of the drug discovery and development process, and multicellular/multitissue systems may serve as more predictive indicators of clinical outcomes. Longer-term applications of 3-D tissue technologies will extend our knowledge of how to build the smallest functional units of a tissue to the fabrication of larger-scale tissues useful for surgical grafts to repair or replace damaged tissues and organs in the body. What are the next steps in the evolution of bioprinting? The first step is scaling up and down - increasing the resolution of specific features while advancing fabrication hardware and techniques to produce larger-scale tissues. The next, enhancing the complexity of designs - building the tool set that enables conceptual or visual inputs to be translated rapidly to executable bioprinting programs that select from a library of bio-ink building blocks to translate the vision into reality.

Link: http://www.rdmag.com/articles/2013/08/3-d-printing-life-science-applications

Source:
https://www.fightaging.org/archives/2013/08/a-short-overview-of-3-d-printing-in-tissue-engineering.php

The British Science Festival will be held in Newcastle a few weeks from now. One of the events has Aubrey de Grey of the SENS Research Foundation, advocate and coordinator for rejuvenation research, debating Tom Kirkwood, one of the leading figures in the mainstream faction of the aging research community who think that there isn't much hope for rapid progress to rejuvenation. Those researchers see the best available path forward as one of modestly slowing aging through replication of known metabolic or genetic alterations associated with natural variations in longevity, such as those involved in the response to calorie restriction - but even this will be a long time in realization, a slow grind towards incremental improvements.

I agree with the viewpoint that attempts to safely slow aging in humans will be very hard indeed. Success requires a much greater understanding of metabolism and aging than presently exists, and it's not unreasonable to suggest that decades and many billions of dollars lie between us and even the first prototype drugs to slightly slow aging. However, slowing aging by altering genes and metabolism is not the only approach that can be taken - indeed it's probably the worst of viable scientific approaches to extending healthy life. It's exceedingly costly, produces marginal results, and therapies that can slow ongoing aging are of little to no use for people who are already old and frail.

In this Kirkwood represents the old mainstream of standardized drug discovery and marginal, unambitious process in medicine. De Grey represents the disruptive future of medical technology, his SENS vision and ongoing research being one of a number of entirely new paradigms for health and aging that are winning over an increasing fraction of the research community. The times are changing, and every new wave of development is met by skepticism from those in the mature industries it will replace. We should aim for rejuvenation through periodic repair of cellular damage: it will like take no longer, will quite possibly be cheaper than trying alter ourselves to slow aging, and will be very beneficial for people who are already old when these therapies are introduced.

Life Without Ageing - Two Contrasting Visions Of An Ageing World

EVENT: Life Without Ageing - Two contrasting visions of an ageing world
DATE: Monday 9th September TIME: 13.00 - 14.30
VENUE: Fine Art Building Lecture Theatre, Newcastle, UK

Is a cure for ageing within reach in our own lifetimes?

Biomedical gerontologist Dr Aubrey de Grey, Chief Science Officer of the SENS Research Foundation will be joining Professor Tom Kirkwood CBE, Associate Dean for Ageing at Newcastle University to debate a 'Life Without Ageing'. In this event, chaired by Dr Sir Tom Shakespeare, Aubrey de Grey will suggest that a "cure" for ageing is within reach in our own lifetimes, while Tom Kirkwood will argue that such a goal is not only unrealistic but distorts what should be the real research priorities of an ageing world.

Dr de Grey's research proposes that eliminating ageing as a cause of debilitation and death in mankind can be achieved within just a few decades through his proposed 'Strategies for Engineered Negligible Senescence'; a term coined by De Grey in his first book The Mitochondrial Free Radical Theory. Countering this is Professor Kirkwood, a former BBC Reith Lecturer, whose research is around healthy ageing and improving life in old age by looking at the prevention of age associated factors, such as frailty, disability and age related disease, and by helping to change society's attitudes towards ageing.

The tantalising idea of living forever is as old as humanity, but can modern science really hope to consign the ageing process to history? Life Without Ageing promises to be a fascinating insight into modern day ageing research and the opposing visions of an ageing world. At the end of the debate the floor will be opened, giving the audience opportunity to put questions to the speakers and take part in what should be a lively discussion.

If you take a careful look at the festival site page for the debate, you'll see that it's possible to submit questions for the speakers. If you intend to go in person, it looks like registration is required, but it's otherwise a free event.

Source:
https://www.fightaging.org/archives/2013/08/life-without-ageing-aubrey-de-grey-and-tom-kirkwood-to-debate-longevity-science-at-the-british-science-festival.php

Long term calorie restriction lowers the risk of cancer in addition to extending life in laboratory animals. Here researchers show that short term calorie restriction appears to augment the effectiveness of treatments for an existing cancer:

While previous studies suggest a connection between caloric intake and the development of cancer, scientific evidence about the effect of caloric intake on the efficacy of cancer treatment has been rather limited to date. When humans and animals consume calories, the body metabolizes food to produce energy and assist in the building of proteins. When fewer calories are consumed, the amount of nutrients available to the body's cells is reduced, slowing the metabolic process and limiting the function of some proteins. These characteristics of calorie restriction have led researchers to hypothesize that reducing caloric intake could potentially help inhibit the overexpression of the protein Mcl-1, an alteration associated with several cancers.

Researchers conducted a series of experiments in mice developing lymphoma resembling Burkitt's lymphoma and diffuse large B-cell lymphoma, two human cancers of the white blood cells. The team began by separating the mice into two categories: those who would receive a regular diet and those who would receive a reduced-calorie diet (75 percent of normal intake) for the duration of the experiment. After the mice consumed either a regular or a reduced-calorie diet for one week, researchers then further divided the mice into four groups according to the treatment they would receive for the following 10 days. Of the two groups of mice that received a normal diet, one (the control group) did not receive treatment and the other received treatment with an experimental targeted therapy, ABT-737, designed to induce cancer cell death. Of the two groups of mice who received a reduced-calorie diet, one did not receive treatment and the other received ABT-737. On day 17 of the experiment, both treatment and calorie restriction ended, and mice had access to as much food as they desired.

Investigators observed that neither treatment with ABT-737 nor calorie restriction alone increased the survival of mice over that of the other mice; however, the combination of ABT-737 and calorie restriction did. Median survival was 30 days in the control group that received a regular diet and no treatment, 33 days in mice that received a regular diet and treatment with ABT-737, 30 days in mice that received a reduced-calorie diet without treatment, and 41 days in mice that received a reduced-calorie diet and treatment with ABT-737. Shortly after this experimental period, investigators also observed that the combination of calorie restriction and ABT-737 reduced the number of circulating lymphoma cells in the mice, suggesting that the combination sensitized the lymphoma cells to treatment.

Link: http://hematology.org/News/2013/10958.aspx

Source:
https://www.fightaging.org/archives/2013/08/calorie-restriction-as-a-means-to-augment-cancer-therapies.php

In recent years researchers have demonstrated a number of ways to improve memory in old laboratory mice. Here is another:

If you forget where you put your car keys and you can't seem to remember things as well as you used to, the problem may well be with the GluN2B subunits in your NMDA receptors. And don't be surprised if by tomorrow you can't remember the name of those darned subunits. They help you remember things, but you've been losing them almost since the day you were born, and it's only going to get worse. An old adult may have only half as many of them as a younger person.

Cognitive decline with age is a natural part of life, and scientists are tracking the problem down to highly specific components of the brain. Separate from some more serious problems like dementia and Alzheimer's disease, virtually everyone loses memory-making and cognitive abilities as they age. The process is well under way by the age of 40 and picks up speed after that. But of considerable interest: It may not have to be that way. "These are biological processes, and once we fully understand what is going on, we may be able to slow or prevent it."

In recent research [scientists] used a genetic therapy in laboratory mice, in which a virus helped carry complementary DNA into appropriate cells and restored some GluN2B subunits. Tests showed that it helped mice improve their memory and cognitive ability. The NMDA receptor has been known of for decades. [It] plays a role in memory and learning but isn't active all the time - it takes a fairly strong stimulus of some type to turn it on and allow you to remember something. The routine of getting dressed in the morning is ignored and quickly lost to the fog of time, but the day you had an auto accident earns a permanent etching in your memory.

Within the NMDA receptor are various subunits, [and] research keeps pointing back to the GluN2B subunit as one of the most important. Infants and children have lots of them, and as a result are like a sponge in soaking up memories and learning new things. But they gradually dwindle in number with age, and it also appears the ones that are left work less efficiently. "The one thing that does seem fairly clear is that cognitive decline is not inevitable. It's biological, we're finding out why it happens, and it appears there are ways we might be able to slow or stop it, perhaps repair the NMDA receptors. If we can determine how to do that without harm, we will."

Link: http://oregonstate.edu/ua/ncs/archives/2013/aug/cognitive-decline-age-normal-routine-%E2%80%93-not-inevitable

Source:
https://www.fightaging.org/archives/2013/08/another-way-to-improve-memory-in-old-mice.php

It is human nature to be capable of committing acts of great evil or economic self-destruction for years on end, and especially in groups. We are not at all far removed at the moment from large-scale genocides, collapsed kleptocracies, meaningless prohibitions, and more. So it's probably unsafe to assume that no state will outright ban the extension of healthy life via medicine in the future: there are more than enough examples of human collectives acting against the long-term self-interest of all their members for decades, and that becomes ever more likely if those at the top invent the means to profit personally from a widespread destruction of life and wealth.

For all that, I do think it's an unlikely outcome. The more plausible outcome is the one that is taking place right now: great economic harm to the pace and breadth of medical development through heavy, centralized regulation. Enormous, entirely unnecessary costs and very high barriers to entry are imposed on clinical applications of medicine, which ensures that a great deal of possible, plausible research and development never happens. Worse, in a system in which all that is not expressly permitted is forbidden - which is exactly the case for the FDA and similar regulatory bodies elsewhere in the world - radically different new technologies such as the means to treat aging are restricted by default, without any politician or bureaucrat having to raise a finger. The entire system of regulation must be changed to even allow them to be considered: which means more cost, more delay, and more work suppressed because it isn't cost-effective to undertake.

Here the possibility of future restrictions on rejuvenation therapies is considered by someone who is more supportive of the existence of a large state than I am. They see the solution as working within the system, being a petitioner to power to beg for the chance to be free enough to make the world a better place. I'm not sure that this has ever had a good record of success over the long term, certainly not when compared to revolution or the establishment of new colonies far enough distant from the state to be largely free from its bureaucracy:

Most laypeople with an opinion [on] biogerontology assume "[life extension] treatments will be centuries in the future", actual specialists with a medical background tend to be more 'optimistic' and postulate some for of accessibility of these treatments somewhere later this century. I'll abbreviate "Life Extension" as LE and Rejuvenation as RE.

The human that has singlehandedly saved most lives world wide may very well have been Maurice Hilleman. In the late 19th to mid 20th century there was a small number of cynics who insisted that vaccinations (and other treatments intended to make people live longer lives) would contribute to Malthusian overpopulation. It is interesting to realize that many of these objections were based on class-prejudice and racism. People who objected to child vaccinations tended to not like poor people very much, and didn''t want 'their' world overrun by the kind of people they took offense to. These sentiments are by no means dead. A very common objection to the mere realization of RE/LE treatments is that "the world would quickly overpopulate". When quizzed strikingly many people today insist that RE/LE might "have to be declared illegal to avoid an overpopulation disaster". These people seem to be unable to infer comparisons from earlier Life Extension treatments (clean drinking water, sanitation, healthy diets, environmental protection laws, vaccinations) from which they benefited, and regard Biogerontological Life Extension as something different altogether.

The process of development of actual "biological immortality" is likely to be a long trajectory of dead ends and catastrophes. The beta stage of life extension may come with painful episodes and failures. Early adopters may end up forking out large sums of private capital for treatments that may or may not work. If earliest stage regenerative treatments were to emerge in the 2020s it may be decades before these treatments would end up safe, affordable, comfortable and easy to use. What is worse - such treatments don't have a convenient fit in the current medical corporate sector. What does a LE or RE treatment actually do? Does it make people less dependent on other medical treatments? If that is the case many established medical conglomerates may very well vehemently object against these treatments, and declare them "snake oil" or "pseudoscience". It is thus quite likely that on the earliest years of emerging LE/RE many consumers may reject these treatments basing their choices on vicious and deceptive media campaigns.

Link: http://ieet.org/index.php/IEET/more/suntzu20130801

Source:
https://www.fightaging.org/archives/2013/08/considering-state-opposition-to-life-extension-technologies.php

Some opponents of increased human healthy longevity argue that if we begin to live for far longer than the present human life span then progress in technology will slow to a crawl. This is often presented as a variation on the stagnation argument: that long-lived people will cling to their ideas and their positions for decades or centuries, resisting all change. It is true that human nature comes with a strong conservative streak, and all change is opposed. But despite that fact change nonetheless happens on a timescale quite short in comparison to human life spans: leaders come and go, like fashions, and revolutions, and changes of opinion, and sweeping redefinitions in culture and society. Rare indeed are those that manage to last for a couple of decades, never mind longer. This pace of change in human affairs is essentially the same as that of the ancient world, despite our much greater adult life expectancy in comparison to the classical Greek period or Roman empire.

If we want to look at raw correlations on the other hand, it seems that the technologies needed to extend healthy life go hand in hand with an increased rate of technological progress. Longevity has made the human world become wealthier and run faster, opening doors of opportunity rather than closing them. The only way to increase the healthy human life span is through the creation of a broad pyramid of enabling technologies that in turn lead to faster progress in all fields, not just medicine. Computing is the present dominant enabler, for example, not just for biotechnology but also for almost all other fields of endeavor. If human nature to date has failed to hold back the tide of progress, I'd say it has little chance at doing so in the future: progress is only speeding up.

As is pointed out in the article excerpted below, people change throughout their lives. This also is the same as in the times of antiquity, despite much longer life spans. Human nature is human nature, and the caricature of inflexible, static old people is just that: a caricature. Minds change, and where the elderly are in fact forced into smaller and smaller circles it is largely through disability and frailty, not choice: the failing body and mind narrow the accessible vista, not the lack of will.

Combatting the "Longer Life Will Slow Progress" Criticism

We are all still children. As far as the Centenarian is concerned, the only people to have ever lived have been children - and we have all died before our coming of age. What if humans only lived to age 20? Consider how much less it would be possible to know, to experience, and to do. Most people would agree that a maximum lifespan of 20 years is extremely circumcising and limiting - a travesty. However, it is only because we ourselves have lived past such an age that we feel intuitively as though a maximum lifespan of 20 years would be a worse state of affairs than a maximum lifespan of 100. And it is only because we ourselves have not lived past the age of 100 that we fail to have similar feelings regarding death at the age of 100. This doesn't seem like such a tragedy to us - but it is a tragedy, and arguably one as extensive as death at age 20.

The current breadth and depth of the world and its past are far too gargantuan to be encompassed by a mere 100 years. If you really think that there are only so many things that can be done in a lifetime, you simply haven't lived long enough or broadly enough. There is more to the wide whorl of the world than the confines and extents of our own particular cultural narrative and native milieu.

Luckily, functional decline as a correlate of age is on the way out. We will live to 100 not in a period of decline upon hitting our mid-twenties, but in a continuing period of youthfulness. There are no longevity therapies on the table that offer to truly prolong life indefinitely without actually reversing aging. Thus, one of the impediments preventing us from seeing death at 100 as a tragedy, as dying before one's time, will be put to rest as well. When we see a 100 year old die in future, they will have the young face of someone who we feel today has died before their time. We won't be intuitively inclined to look back upon the gradual loss of function and physiological-robustness as leading to and foretelling this point, thereby making it seem inevitable or somehow natural. We will see a terribly sad 20 year old, wishing they had more time.

It seems to me a truism that we get smarter, more ethical and more deliberative as we age. To think otherwise is in many cases derivative of the notion that physiology and experience alike are on the decline once we "peak" in our mid-twenties, downhill into old age - which does undoubtedly happen, and which inarguably does cause functional decline. But longevity therapies are nothing more nor less than the maintenance of normative functionality; longevity therapies would thus not only negate the functional decline that comes with old age, [but also] the source of the problem arguably at the heart of the concern that longer life will slow progress.

Increasing longevity will not bring with it prolonged old-age, a frozen decay and decrepit delay, but will instead prolong our youthful lives and make us continually growing beings, getting smarter and more ethical all the time.

Lastly, this thought: so what if increased life spans did slow progress? Even in the hypothetical world in which that did look even remotely plausible, it is still the case that for so long as the pace of longevity is greater than the slowdown, everyone still comes out ahead. Being alive and in good health is the important thing: given that, the only thing that matters with regard to further technological progress is whether it is happening fast enough to keep you alive and in good health. Everything else in life is what you make of it.

Source:
https://www.fightaging.org/archives/2013/08/opposing-the-argument-that-increased-longevity-will-slow-progress-and-is-therefore-undesirable.php

Mitochondria are the power plants of the cell, generating chemical fuel stores that can be used to power cellular processes. They are important in aging, and this has a lot to do with the generation of reactive oxygen species (ROS) that happens as a side-effect of their operation. Researchers have shown that benefits to health and longevity can be realized in laboratory animals by targeting antioxidants to mitochondria in order to soak up some ROS before they cause harm. Other research focuses on repairing the damage that mitochondria inflict upon themselves this way, so as to stop it from contributing to degenerative aging.

There is general agreement that mitochondria play an important role in the aging process, but the role of mitochondrial oxidative stress remains controversial. Most previous work looking at mitochondrial oxidative stress has focused on damage to DNA, proteins, and lipids with age or in response to manipulation of cellular antioxidants. The interaction between oxidative damage and aging has been called into question in recent years by studies demonstrating little effect on aging and lifespan in mice with genetically modified antioxidant systems. A notable exception is the life extension and protection against multiple diseases in mice that express catalase in the mitochondria, which suggests that the cellular location and type of reactive oxygen species is an important factor.

Our laboratory is interested in whether redox inhibition of mitochondrial function contributes to age-related energy deficits in vivo in mouse and human skeletal muscle. [We] tested this hypothesis using a mitochondrial targeted peptide, SS-31, known to reduce mitochondrial H2O2 production.

SS-31 reduced the high mitochondrial H2O2 production from aged permeabilized muscle fibers [but] had no effect on young fibers. In the aged mice, one hour after in vivo treatment with SS-31 the cellular redox status [was] more reduced. This was accompanied by improved mitochondrial [function] in vivo in the skeletal muscle, while there was no effect on the mitochondrial energetics in young skeletal muscle. In addition to the improvements in muscle energetics, one hour and one week of SS-31 treatment resulted in improved muscle performance and increased exercise tolerance, respectively, in the old mice.

This rapid reversal of in vivo energy deficits supports the hypothesis that mitochondrial deficits in aged skeletal muscle are, at least in part, due to reversible redox sensitive inhibition. Thus assessing the role of mitochondrial oxidative stress in aging and disease will require careful attention to changes to the in vivo redox environment and the mechanisms by which these changes can affect cell function.

Link: http://impactaging.com/papers/v5/n8/full/100590.html

Source:
https://www.fightaging.org/archives/2013/08/targeting-redox-biology-to-reverse-mitochondrial-dysfunction.php

The thymus helps to generate the cell populations of your immune system when young, but it atrophies - a process called involution - quite early in adult life. Many of the frailties of aging have their roots in the age-related decline of the immune system. It fails with age in large part because it is a size-limited population of cells, and ever more of those cells become inappropriately configured and unable to respond to new threats. One of the proposed methods for dealing with this issue is to restore the thymus, and therefore create a stream of new immune cells to take up the slack. Transplanting a thymus from a young mouse into an old mouse improves the immune system and extends life, for example.

For human medicine, the focus is on finding ways to tissue engineer a new thymus from the patient's own cells, or spur regrowth of the existing involuted thymus. Here is an example of progress in the research and development needed for thymic tissue engineering - if you want to build a thymus, you first have to be able to reliably generate large numbers of the right sort of cells. Work on that goal is still in progress:

Thymus transplantation has great clinical potential for treating immunological disorders, but the shortage of transplant donors limits the progress of this therapy. Human embryonic stem cells (hESCs) are promising cell sources for generating thymic epithelial cells. Here, we report a stepwise protocol to direct the differentiation of hESCs into thymic epithelial progenitor-like cells (TEPLCs) by mimicking thymus organogenesis with sequential regulation of Activin, retinoic acid, BMP, and WNT signals.

The hESC-derived TEPLCs expressed the key thymic marker gene FOXN1 and could further develop in vivo into thymic epithelium expressing the functional thymic markers MHC II and AIRE upon transplantation. Moreover, the TEPLC-derived thymic epithelium could support mouse thymopoiesis in T-cell-deficient mice and promote human T cell generation in NOD/SCID mice engrafted with human hematopoietic stem cells (hHSCs). These findings could facilitate hESC-based replacement therapy and provide a valuable in vitro platform for studying human thymus organogenesis and regeneration.

Link: http://dx.doi.org/10.1016/j.stem.2013.06.014

Source:
https://www.fightaging.org/archives/2013/08/steps-towards-tissue-engineered-thymus.php

The success of Kickstarter and conceptually similar entities (IndieGoGo, AngelList, and so forth) as fundraising communities has more than adequately demonstrated that crowdfunding works very well in an environment of low-cost, ubiquitous communication and open data. All the old centralized time-proven activities of fundraising in for-profit business can in fact be distributed, turned inside out, and disintermediated. New middle men arise in this process of disruptive change, such as Kickstarter, but the future will see their dominance vanish in favor of open protocols and marketplaces with some sort of an ecosystem of optional gatekeepers and reviewers. This is exactly the same as the transition from early dial-up services and their walled gardens to the open internet, and seems to be something of an inevitability.

Can this be made to work for science and research? Therein lies the question. At the high level, it seems as though the answer is obviously yes: it's all just money, and money is presently invested in research. But at the detail level research is a very different thing from funding a new artwork or widget: it has a much longer time horizon, a far greater degree of uncertainty, and the funders don't walk away at the end with a new widget. A number of companies are presently attempting to find the magic recipe by which crowsourced science funding can be made work in a Kickstarter-like fashion.

Clearly crowdfunding for specific research goals is possible. There are numerous examples of success in the past decade beyond those I'll mention here. The Methuselah Foundation and SENS Research Foundation grew out of crowdfunding initiatives, raising money from hundreds of donors from the transhumanist community and other supporters of longevity science. The advocacy community of Longecity raises modest sums for specific life science research projects connected to longevity and related medical technologies. But these are tailored projects, integrated with specific interest communities: not the same thing at all as building a successful marketplace for diverse forms of project and community.

Crowdfunding intersects with another important trend that arises with ubiquitous, low-cost communication and openly accessible data, which is the distribution of effort in large projects. Complex initiatives can now be undertaken piecemeal by geographically dispersed groups who share a common interest. The open source software development community is far ahead of the rest of the world in this respect: many vital and important software projects have evolved in a worldwide fashion, with self-organizing collaborators who will never meet in person. Science is moving in the same direction: lots of data, lots of complex software, data becoming more open, and more distributed collaboration between researchers in different parts of the world.

What medical science has that the software industry does not is a vast and pervasive edifice of regulation, wherein largely unaccountable regulators insist on centralization and the imposition of enormous costs on research and its application in the form of new therapies and medical technologies. Regulation opposes movement to a more distributed research and development industry in which even exceedingly rare diseases will be worked on by someone, somewhere with a vested interest. Higher costs always mean that marginal work suffers, vanishes entirely, or takes place in black and grey markets with all their attendant issues. It is enormously harmful, and that harm is largely invisible: the technologies not developed, the progress not made, the dead in their millions who might have had a chance at longer lives.

The article quoted below offers some thoughts on all of this in the context of cancer research and proto-crowdfunding efforts that have aimed to spur research and development in therapies for very rare forms of cancers, those that present regulation makes it unprofitable to work on. The points raised are also applicable to the situation for aging and rejuvenation research, however, which is also a collection of related minority fields that are shut out from clinical application by the decisions of regulators.

Can We Build A Kickstarter For Cancer?

Building large analytical databases to mine clinical and molecular data, and scan the scientific literature to identify better treatments for cancer patients is happening today. But what about patients who fall outside what we already know - whose cancer subtypes haven't been discovered yet, and who don't have access to the technologies that could make a difference in unraveling the aberrations driving their cancers? The technology to unravel the molecular drivers of cancer is, for the most part, available today: "-omics" technologies for screening tumor samples from patients and comparing them to healthy tissue samples to pick out cancer-specific mutations; diagnostics that can track patients' response to treatment in real time at a molecular level; and Web-based tools and apps [that] patients and community oncologists can use to guide treatment decisions (and feed those outcomes, good and bad, back into the research process).

Our current research approach - one drug, one clinical trial, one cancer type at a time - won't generate enough of the information we need to unravel cancer's molecular mysteries at the patient level. And it is too slow, too bureaucratic, and too expensive to be sustainable, given the number of compounds we have to test and the limited pool of patients who participate in clinical trials. Only about 3% of all cancer patients participate in cancer clinical trials, and those patients - because of restrictive inclusion/exclusion criteria - are often very different (i.e., healthier) than the average cancer patient, who is likely to be in poorer health and have one or more co-morbidities (obesity, diabetes, etc.). This limits the applicability of even the best drug guidelines based on classical trials for real-world patients. Classical clinical trials lead to a "tyranny of the averages," rather than helping us to - as in the case of cancer - disassemble complex diseases that might share the same clinical symptoms (and which we happen to call cancer or diabetes) but which are really molecularly distinct and thus require different treatment approaches.

In short, we won't develop the drugs or complex treatment regimens we need to for truly personalized cancer treatment regimens for patients if we keep doing business as usual. The patients who have the most to gain from this approach are those who have the most to lose today - patients with rare or hard-to-treat cancers, who fail rapidly on standard or even targeted treatments. And it's exactly these patients who will, in all likelihood, be most eager to embrace the risks and promise of Kickstarting their own cancer research.

It's not just cancer: all of modern medicine would benefit from an overturning of the present centralized regulatory structures in order to allow unfettered diversity in fundraising, research, and clinical application. This is exactly the sort of approach that modern communication technologies enable: let there be far more in the way of researchers connecting to the interested small communities among the broader public - as was the case for the Strategies for Engineered Negligible Senescence - and the best of these initiatives, those that manage to obtain support from both the public and the scientific community, will prosper. This, I think, is a far more promising model for the future of research than the stasis, obstructions, and failures of highly regulated, state-funded scientific and medical monoliths.

Source:
https://www.fightaging.org/archives/2013/08/the-intersection-of-kickstarter-style-fundraising-for-research-and-distributed-development-in-complex-problems.php

Researchers here compare the effects of calorie restriction and dietary resveratrol on the pace of sarcopenia, the age-related loss of muscle mass and strength. What I take away from this is that calorie restriction produces meaningful results on this front, albeit modest in comparison to what we'd like to see, and resveratrol doesn't.

Aging is associated with a loss in muscle known as sarcopenia that is partially attributed to apoptosis. In aging rodents, caloric restriction (CR) increases health and longevity by improving mitochondrial function and the polyphenol resveratrol (RSV) has been reported to have similar benefits. In the present study, we investigated the potential efficacy of using short-term (6 weeks) CR (20%), RSV (50 mg/kg/day), or combined CR+RSV (20% CR and 50 mg/kg/day RSV), initiated at late-life (27 months) to protect muscle against sarcopenia by altering mitochondrial function, biogenesis, content, and apoptotic signaling in both glycolytic white and oxidative red gastrocnemius muscle (WG and RG, respectively) of male Fischer 344 x Brown Norway rats.

CR but not RSV attenuated the age-associated loss of muscle mass in both mixed gastrocnemius and soleus muscle, while combined treatment (CR+RSV) paradigms showed a protective effect in the soleus and plantaris muscle. Sirt1 protein content was increased by 2.6-fold in WG but not RG muscle with RSV treatment, while CR or CR+RSV had no effect. PGC-1? levels were higher (2-fold) in the WG from CR-treated animals when compared to ad-libitum (AL) animals but no differences were observed in the RG with any treatment.

These data suggest that short-term moderate CR, RSV, or CR+RSV tended to modestly alter key mitochondrial regulatory and apoptotic signaling pathways in glycolytic muscle and this might contribute to the moderate protective effects against aging-induced muscle loss observed in this study.

Link: http://www.ncbi.nlm.nih.gov/pubmed/23747682

Source:
http://www.fightaging.org/archives/2013/06/calorie-restriction-versus-resveratrol-treatment.php

Calorie restriction is definitely good for you, provided that you maintain an optimal intake of micronutrients in your smaller diet. There is a tremendous weight of evidence for the benefits of calorie restriction in animals and a large weight of evidence for benefits in humans: it improves near all short term measures of health, slows down the progression of near every measure of degenerative aging, and extends healthy life in most species. Research publications are usually more understated in their evaluation of calorie restriction, of course. See this, for example:

Caloric Restriction: Implications for Human Cadiometabolic Health

Evidence from animal studies and a limited number of human trials indicates that calorie restriction has the potential to both delay cardiac aging and help prevent atherosclerotic cardiovascular disease via beneficial effects on blood pressure, lipids, inflammatory processes, and potentially other mechanisms.

The candidate list of mechanisms by which calorie restriction likely delivers its benefits include reduced visceral fat, increased levels of autophagy, altered mitochondrial function, and metabolic changes caused by reduced levels of methionine in the body. All of these on their own have been shown to extend life and improve measures of health in animal studies. Many other measurable changes result from calorie restriction, but identifying which of them are definitively primary and which are definitively secondary is still a work in progress.

Methionine is one of the essential amino acids that your metabolism doesn't manufacture. You have to obtain it in the diet, and it's an essential component for the cellular manufacture of new protein machinery. There are all sorts of studies in mice and rats showing that if you keep the same dietary calorie level but strip out much of the methionine then the animals involved live longer, and exhibit many of the same changes in metabolism as occur from reduced calorie levels. Here is a recent example:

Methionine restriction affects oxidative stress and glutathione-related redox pathways in the rat

Lifelong dietary methionine restriction (MR) is associated with increased longevity and decreased incidence of age-related disorders and diseases in rats and mice. A reduction in the levels of oxidative stress may be a contributing mechanistic factor for the beneficial effects of MR. To examine this, we determined the effects of an 80% dietary restriction of Met on different biomarkers of oxidative stress and antioxidant pathways in blood, liver, kidney and brain in the rat.

Male F-344 rats were fed control (0.86% methionine) or MR (0.17% methionine) diets for up to six months. Blood and tissues were analyzed for [levels of the natural antioxidant] glutathione (GSH). related enzyme activities and biomarkers of oxidative stress. MR was associated with reductions in oxidative stress biomarkers [and] erythrocyte protein-bound glutathione after one month with levels remaining low for at least six months.

Levels of free GSH in blood were increased after 1-6 months of MR feeding whereas liver GSH levels were reduced over this time. In MR rats, GSH peroxidase activity was decreased in liver and increased in kidney compared with controls. No changes in the activities of GSH reductase in liver and kidney and superoxide dismutase in liver were observed as a result of MR feeding. Altogether, these findings indicate that oxidative stress is reduced by MR feeding in rats, but this effect cannot be explained by changes in the activity of antioxidant enzymes.

You might compare the comments above with the two calorie restriction research papers I pointed out earlier today - you'll quickly see the similarities, such as the fact that the behavior of antioxidants and oxidants in metabolism is complex and hard to tie to the observed benefits in health and longevity. All in all it is convincing to argue that methionine sensing is at the heart of the metabolic changes that produce the benefits of calorie restriction:

• Calorie Restriction Versus Resveratrol Treatment
• Reviewing the Literature on Calorie Restriction and Oxidative Stress

From the practical standpoint of day to day effort and willpower, I'd say that that there isn't much difference between eating a calorie restricted diet and a methionine restricted diet. The latter is harder by far to organize, I think. You certainly couldn't do it without a lot of research, extra food preparation, and meal planning, and there are few resources out there to help you short-cut the process. Calorie restriction, on the other hand, just requires you to keep count and be sensible, plus of course to have a willingness to be hungry for some time every day. It's that latter item that most people find a challenge, in this age of ubiquitous, cheap, tasty food. Calorie restriction also has a far greater weight of supporting evidence for benefits to health in humans, which is probably the most important factor of those mentioned here, but every choice you make has trade-offs.

Source:
http://www.fightaging.org/archives/2013/06/a-little-methionine-restriction-research.php

This popular science piece outlines some of the evidence for greater height to come with a penalty to longevity. I believe that the most plausible contribution to this effect has to do with growth hormone metabolism, given the degree to which it is linked to longevity in laboratory animals. Broadly speaking less growth hormone means a longer life in species such as mice. Larger individuals with more growth hormone accumulate damage and dysfunction at a faster pace in all areas: they age more rapidly.

One of the goals for future medicine is to make all such correlations in long term health irrelevant. Advanced medical technology, sufficient to repair the causes of aging, will sweep away the effects of differences in genetics and circumstances. This is something to look forward, as with suitable levels of funding and support the first of these new therapies of rejuvenation might be developed and rolled out by the late 2030s.

Physicians and epidemiologists began studying the link between height and longevity more than a century ago. Early researchers believed that tall people lived longer, [but] in fact in the early 20th century height was [a] reflection of better nutrition and hygiene, which increased longevity. Once the studies were limited to otherwise homogeneous populations, a consensus emerged that short people are longer-lived.

Among Sardinian soldiers who reach the age of 70, for example, those below approximately 5-foot-4 live two years longer than their taller brothers-in-arms. A study of more than 2,600 elite Finnish athletes showed that cross-country skiers were 6 inches shorter and lived nearly seven years longer than basketball players. Average height in European countries closely correlates to the rate of death from heart disease. Swedes and Norwegians, who average about 5-foot-10, have more than twice as many cardiac deaths per 100,000 as the Spaniards and Portuguese, who have an average height just north of 5-foot-5. Tall people rarely live exceptionally long lives. Japanese people who reach 100 are 4 inches shorter, on average, than those who are 75. The countries in the taller half of Europe have 48 centenarians per million, compared to 77 per million in the shorter half of the continent.

Setting aside simple mortality, individual diseases are also more common among tall people. American women above 5-foot-6 suffer recurrent blood clots at a higher rate. Among civil servants in London, taller people have been shown to suffer from more respiratory and cardiovascular illness. And then there's cancer. Height is associated with greater risk for most kinds of cancer, except for smoking-induced malignancies.

Unlike intelligence, which has a merely coincidental relationship with height, there are plausible biological explanations for why short people live longer. Researchers have found that the lungs of taller people don't function as efficiently, relative to their bodies' demands, as those of short people. Explanations for the link between height and other disorders are slightly more speculative, but largely credible. Tall people have more cells, which may increase the chances that some of them will mutate and lead to cancer. The hormones involved in rapid growth may also play a role in cancer development. It's even possible that the foods that lead to fast growth during childhood may increase the likelihood that a person will eventually develop cancer. The link between height and clots probably has to do with the length and weight of the columns of blood that travel between the heart and the body's extremities.

Link: http://www.slate.com/articles/health_and_science/science/2013/07/height_and_longevity_the_research_is_clear_being_tall_is_hazardous_to_your.html

Source:
https://www.fightaging.org/archives/2013/08/the-cost-of-being-tall-is-a-shorter-life-expectancy.php

Young mammals, and occasionally adults, can regenerate lost fingertips. This seems like a good place to learn more about the mechanisms of regeneration, gaining insight into why it is that mammals cannot replicate the feats of limb and organ regeneration exhibited by species such as salamanders and zebrafish. More importantly, researchers hope to find that it is practical to adjust human biology to allow this sort of exceptional regeneration:

If a salamander loses its leg, it can grow a new one. Humans and other mammals are not so fortunate, but we can regenerate the tips of our digits, as long as enough of the nail remains. This was first shown some 40 years ago; today researchers finally reveal why it is that nails are necessary. Working with mice, [researchers] have identified a population of stem cells lying beneath the base of the nail that can orchestrate the restoration of a partially amputated digit. However, the cells can do so only if sufficient nail epithelium - the tissue that lies immediately below the nail - remains.

The process is limited compared with the regenerative powers of amphibians, but the two share many features, from the molecules that are involved to the fact that nerves are necessary. "I was amazed by the similarities. It suggests that we partly retain the regeneration mechanisms that operate in amphibians."

The nail base contains a small population of self-renewing stem cells, which sustain the nail's continuous growth. This ongoing growth depends on signals carried by the Wnt family of proteins - if this signalling pathway is disrupted, mouse nails cannot form. The team found that the same pathway is involved in the regeneration of lost mouse toe tips. After amputation, the Wnt pathway is activated in the epithelium underlying the remaining nail and attracts nerves to the area. Through a protein called FGF2, the nerves drive the growth of mesenchymal cells, which restore tissues such as bone, tendons and muscle. Within five weeks, the digit is good as new.

However, none of this can happen if the digit is amputated too far back, and too much nail epithelium is lost. In such cases, the Wnt pathway is never activated, the nerves do not extend and the other tissues cannot regenerate.

Link: http://www.nature.com/news/how-nails-regenerate-lost-fingertips-1.13192

Source:
http://www.fightaging.org/archives/2013/06/investigating-fingertip-regeneration-in-mammals.php

It is usually the case that the first knee-jerk reaction in opposition to increased human longevity is based on the mistaken belief that life extension technologies would lead to people being ever more frail and decrepit for a very long time. This is far from the case, and it's probably not even possible to cost-effectively engineer a society of long-lived frail people - even if that was the goal to hand. If you are frail and decrepit then you have a high mortality rate due to the level of age-related cellular and molecular damage that is causing the failure and degeneration of your body and its organs. You won't be around for long. No, the only way to engineer longer healthy life is extend the period of youth and vitality, a time in which you have little age-related damage and your mortality rate is very low. Most present strategies are aimed to prolong that period of life, either by slowing the rate at which damage occurs (not so good) or finding ways to periodically repair the damage and thus rejuvenate the patient (much better).

Once people grasp that longevity science is the effort to make people younger for far longer, then the second knee-jerk objection arises. This is the belief that a very long-lived individual would become overwhelmed by boredom: they would run out of interest and novelty. This is by far the sillier objection, and there is absolutely no rational basis for it. Even a few moments of thought should convince you that there is far more to do and learn that you could achieve in a thousand life spans - and it's a little early in the game to be objecting to enhanced longevity on the basis that you can't think of what to do with life span number number 1001.

Considering boredom, futility, meaningless, and related matters, I noticed what appears to be an argument by induction in the article below. Mathemetical induction is a tool used in formal proofs wherein if you can prove that something is generally true for n and n+1 (where n is a natural number), and then show that it is true for 1, then you can conclude it must be true for all natural numbers. If it is true for 1, then it must be true for 1+1 = 2, and true for 2+1 = 3, and so on.

Life Extension Leads to Meaningless Days? NO!

Person X lives a fulfilling and meaningful life for X number of years before that life is terminated by a sudden, massive heart attack.Now, imagine another person whom we shall label (not too creatively) 'Person 2?. Person 2?s life follows the same general path as person 1 with one exception: It is one day longer than person 1?s was. Now ask yourself: Is there any reason to suppose that this day, let us assume it is aTuesday, strikes person 2 as being meaningless despite the fact that all Tuesdays (and indeed every other day in person 2?s past) seemed worth living?

OK, so now imagine yet another person who goes by the label of... yes, you guessed it, Person 3. You can probably also guess that Person 3 lives one day longer than person 2. Once again, I can think of no reason why, where we have two people who live meaningful lives but one lives one day longer, that extra day would not seem worth experiencing. Put another way: If possible would persons 2 and 1 rather not be dead on Wednesday (the last day for person 3) when Monday and all preceding days were worth experiencing? So far as I can see, the answer to that question is, 'yes'. There seems to be no reason why this argument should not hold for any number of hypothetical people, each one of which lives one day longer than the last.

Unfortunately you can't prove conjectures about aspects of human nature with induction (or not yet, at least). What you can do is use it, as above, to mount a more convincing argument. This one is somewhat akin to one of the standard lines in any debate between a person who is in favor of greatly extending healthy life versus someone who isn't.

Advocate: So you are fine with aging and dying?

Deathist: Yes.

Advocate: So you are fine with dying right now, done and finished?

Deathist: Well, no.

Advocate: Why would you think any differently ten days, or a hundred days, or decades from now, if you still had your health and vigor?

Deathist: Um...

There seems to be a strange disconnect in many people's minds, in which they are vigorously in favor of being alive right this instant or next week, but they nonetheless believe that their future self of years ahead will be of a different opinion and want to die. Now if you're on the downhill slope of aging, in great pain, and your body is falling apart, desiring a stopping point is not unreasonable. (With the best of present options for those in that position being cryonics). But in a world of rejuvenation therapies, in which older life is just as healthy, low-risk, and full of possibility as younger life, what mysterious thing is going make people want to die?

Source:
http://www.fightaging.org/archives/2013/06/arguing-by-induction-for-an-absence-of-boredom-in-an-ageless-greatly-extended-healthy-life.php