The feasibility of reversing human aging within a matter of decades has traditionally been dismissed by all professional biogerontologists, on the grounds that not only is aging still poorly understood, but also many of those aspects that we do understand are not reversible by any current or foreseeable therapeutic regimen. This broad consensus has recently been challenged by the publication, by five respected experimentalists in diverse subfields of biogerontology together with three of the present authors, of an article (Ann NY (...) Acad Sci 959, 452–462) whose conclusion was that all the key components of mammalian aging are indeed amenable to substantial reversal (not merely retardation) in mice, with technology that has a reasonable prospect of being developed within about a decade. Translation of that panel of interventions to humans who are already alive, within a few decades thereafter, was deemed potentially feasible (though it was not claimed to be likely). If the prospect of controlling human aging within the foreseeable future cannot be categorically rejected, then it becomes a matter of personal significance to most people presently alive. Consequently, we suggest that serious public debate on this subject is now warranted, and we survey here several of the biological, social and political issues relating to it. BioEssays 24:667–676, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Over recent years, evidence has been accumulating in favour of the free radical theory of aging, first proposed by Harman. Despite this, an understanding of the mechanism by which cells might succumb to the effects of free radicals has proved elusive. This paper proposes such a mechanism, based on a previously unexplored hypothesis for the proliferation of mutant mitochondrial DNA: that mitochondria with reduced respiratory function, due to a mutation or deletion affecting the respiratory chain, suffer less frequent lysosomal degradation, (...) because they inflict free radical damage more slowly on their own membranes. Once such a mutation occurs in a mitochondrion of a non‐dividing cell, therefore, mitochondria carrying it will rapidly populate that cell, thereby destroying the cell's respiratory capability. The accumulation of cells that have undergone this transition results in aging at the organismal level. The consistency of the hypothesis with known facts is discussed, and technically feasible tests are suggested, of both the proposed mechanism and its overall contribution to mammalian aging. (shrink)

As a leader of the crusade to defeat aging, working to demonstrate both its feasibility and its desirability, I am often seen as an implacable opponent of all arguments that defend aging and criticize this crusade. This is an oversimplification.

The 2013 Rostock Symposium on Systems Biology and Bioinformatics in Aging Research was again dedicated to dissecting the aging process using in silico means. A particular focus was on ontologies, as these are a key technology to systematically integrate heterogeneous information about the aging process. Related topics were databases and data integration. Other talks tackled modeling issues and applications, the latter including talks focussed on marker development and cellular stress as well as on diseases, in particular on diseases of kidney (...) and skin. (shrink)

The feasibility of reversing human aging within a matter of decades has traditionally been dismissed by all professional biogerontologists, on the grounds that not only is aging still poorly understood, but also many of those aspects that we do understand are not reversible by any current or foreseeable therapeutic regimen. This broad consensus has recently been challenged by the publication, by five respected experimentalists in diverse subfields of biogerontology together with three of the present authors, of an article (Ann NY (...) Acad Sci 959, 452–462) whose conclusion was that all the key components of mammalian aging are indeed amenable to substantial reversal (not merely retardation) in mice, with technology that has a reasonable prospect of being developed within about a decade. Translation of that panel of interventions to humans who are already alive, within a few decades thereafter, was deemed potentially feasible (though it was not claimed to be likely). If the prospect of controlling human aging within the foreseeable future cannot be categorically rejected, then it becomes a matter of personal significance to most people presently alive. Consequently, we suggest that serious public debate on this subject is now warranted, and we survey here several of the biological, social and political issues relating to it. BioEssays 24:667–676, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

On the ethics of extending human life: healthy people have a right to carry on livingHumanity has long demonstrated a paradoxical ambivalence concerning the extension of a healthy human lifespan. Modest health extension has been universally sought, whereas extreme health extension has been regarded as a snare and delusion—a dream beyond all others at first blush, but actually something we are better off without. The prevailing pace of biotechnological progress is bringing ever closer the day when humanity will be able (...) to act on the latter view by rejecting a clear and present opportunity for much longer healthy lives. Indeed, some biogerontologists contend that that day has already arrived, to the extent that our hesitation in embarking on a vigorous “war on ageing” is already delaying the point at which a cure for ageing will be developed. Here I consider whether our present caution concerning the wisdom of truly curing ageing is likely to survive the increased scrutiny that it will receive in coming years as a result of these technical advances. I conclude that it will not, because of its irreconcilability with values that are more deeply held by the large majority of humanity than any values that argue against the quest for a cure. I further conclude that all the major current reasons given for not curing ageing are mere crutches to help us cope with the immutability of ageing that we have been brought up to accept. Our failure to set aside such irrationality is already shortening potential longevity—quite probably of those already alive today—to a staggering degree. Once we realise this, our determination to consign human ageing to history will be second …. (shrink)

This article is an ethical evaluation of the SENS bio-engineering program of Aubrey de Grey. After a general introduction, section 2 is a refutation of the claim that not to cure aging is immoral. It analyses the conceptual identification made by de Grey between “aging” and “disease.” This identification has important moral implications. It is argued that from a physiological standpoint the identification makes sense but from an evolutionary point of view it is highly questionable. Section 3 (...) is a refutation of the answer given by transhumanists to objections concerning the desirability of physical immortality. It is argued that the objections have not been adequately answered. (shrink)

This article proposes an original analysis of the international debate on climate change through the use of digital methods. Its originality is twofold. First, it examines a corpus of reports covering 18 years of international climate negotiations, a dataset never explored before through digital techniques. This corpus is particularly interesting because it provides the most consistent and detailed reporting of the negotiations of the United Nations Framework Convention on Climate Change. Second, in this paper we test an original approach to (...) text analysis that combines automatic extractions and manual selection of the key issue-terms. Through this mixed approach, we tried to obtain relevant findings without imposing them on our corpus. The originality of our corpus and of our approach encouraged us to question some of the habits of digital research and confront three common misunderstandings about digital methods that we discuss in the first part of the article. In addition to reflecting on methodology, however, we also wanted to offer some substantial contribution to the understanding of UN-framed climate diplomacy. In the second part of the article we will therefore introduce some of the preliminary results of our analysis. By discussing three visualizations, we will analyze the thematic articulation of the climatic negotiations, the rise and fall of these themes over time and the visibility of different countries in the debate. (shrink)

Biogerontologist Aubrey de Grey has suggested that one of the reasons we as a society invest so little in research on combating aging is because we are in an intellectual trance. We think the effort will be futile: aging is immutable, so why try? A healthy skepticism can be a good thing but it is a major mistake to bet against the irresistible force of inexorable technological progress. Over the next few decades, nanotechnology will come to play a (...) pivotal role in the solution to the problem of human aging. Medical nanorobotics, if it can be made to work, can unquestionably offer convenient solutions to all known causes of age-related damage and most likely can also successfully address any new causes of senescence that remain undiscovered today. (shrink)

BackgroundThe ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines are widely endorsed but compliance is limited. We sought to determine whether journal-requested completion of an ARRIVE checklist improves full compliance with the guidelines.MethodsIn a randomised controlled trial, manuscripts reporting in vivo animal research submitted to PLOS ONE (March–June 2015) were randomly allocated to either requested completion of an ARRIVE checklist or current standard practice. Authors, academic editors, and peer reviewers were blinded to group allocation. Trained reviewers performed outcome adjudication (...) in duplicate by assessing manuscripts against an operationalised version of the ARRIVE guidelines that consists 108 items. Our primary outcome was the between-group differences in the proportion of manuscripts meeting all ARRIVE guideline checklist subitems.ResultsWe randomised 1689 manuscripts (control: n = 844, intervention: n = 845), of which 1269 were sent for peer review and 762 (control: n = 340; intervention: n = 332) accepted for publication. No manuscript in either group achieved full compliance with the ARRIVE checklist. Details of animal husbandry (ARRIVE subitem 9b) was the only subitem to show improvements in reporting, with the proportion of compliant manuscripts rising from 52.1 to 74.1% (X2 = 34.0, df = 1, p = 2.1 × 10−7) in the control and intervention groups, respectively.ConclusionsThese results suggest that altering the editorial process to include requests for a completed ARRIVE checklist is not enough to improve compliance with the ARRIVE guidelines. Other approaches, such as more stringent editorial policies or a targeted approach on key quality items, may promote improvements in reporting. (shrink)

Whether extrovertive, introvertive, or some further hybrid, the process of the soul touching the fullness of its divine origins is itself undergoing transformation in the twenty-first-century cultural matrices of Israel. A remarkable exemplar of devotional Hebrew cultures can be found within the hybrid networks of haredi worlds in Israel today. R. Yitzhaq Maier Morgenstern, author of Yam ha-okhmah, Netiv ayyim, and De'i okhmah le-nafshekha, is arguably the most innovative mystical voice in Israel. Why are his works resonating so strongly both (...) inside and outside their haredi communities of origin? How is his innovative thinking affecting the devotional praxis of Devekut both inside and outside the unfolding Hasidic networks? This exploration of mystical apperception through Devekut builds upon studies of Garb, Huss, and Meir, while challenging the idea that Morgenstern's expanding impact is solely a function of his mystical-magical charisma and hypernomian spiritual practice. This study argues that it is Morgenstern's hybridized thinking through key theoretical issues in Kabbalah and Hasidism as they apply to the lived practice of a devotional life of Devekut that will likely remain his strongest innovation and contribution to contemporary Jewish mysticism. (shrink)

Spinoza: Moral Philosophy Like many European philosophers in the early modern period, Benedict de Spinoza developed a moral philosophy that fused the insights of ancient theories of virtue with a modern conception of humans, their place in nature, and their relationship to God. Unlike many other authors in this period, however, Spinoza was strongly … Continue reading Spinoza: Moral Philosophy →.

Some maladaptive thought processes are characterized by reflexive and habitual patterns of cognitive and emotional reactivity. We review theoretical and empirical work suggesting that mindfulness—a state of nonjudgmental awareness of the present moment—can facilitate the discontinuation of such automatic mental operations. We propose a framework that suggests a series of more specific mechanisms supporting the de-automatizing function of mindfulness. Four related but distinct elements of mindfulness (awareness, attention, focus on the present, and acceptance) can each contribute to de-automatization through subsequent (...) processes, including discontinuing automatic inference, enhancing cognitive control capacity, facilitating metacognitive insight, and preventing suppression or thought distortion. De-automatizing can, in turn, allow enhancement of adaptive self-control ability and increased well-being. (shrink)

A philosophical frame for violence against women and girls creates unique opportunities to deepen our understanding of the embodied consequences of men’s violence. Using the seemingly innocuous example of being told to “cheer up” or “smile”, we draw on Simone de Beauvoir and Franz Fanon’s work on recognition to suggest that a phenomenological approach to sexual violence may help to voice previously inarticulable harms. The dual frame of Beauvoir and Fanon also highlights the need for philosophical work on sexual violence (...) to take account of the insights of intersectionality. (shrink)

The prime number theorem, established by Hadamard and de la Vallée Poussin independently in 1896, asserts that the density of primes in the positive integers is asymptotic to 1/ln x. Whereas their proofs made serious use of the methods of complex analysis, elementary proofs were provided by Selberg and Erdos in 1948. We describe a formally verified version of Selberg's proof, obtained using the Isabelle proof assistant.

Voor wie geen troost kan vinden in het al-te-menselijke, valt hoop te putten uit de natuur. Daarvan getuigt ook Thomas Hardy’s gedicht op de nachtegaal. Het dier is verminkt door mensen, maar het zingt nog altijd en bezorgt de mens levensvreugde.

This is a section of Mr. Gray's recent paper read before The Philosophers' Academy covering "The Catholic Movement in France and the Philosophy of de Lamennais".Complete ignorance of the system of the Medieval Schoolmen seems responsible for the contempt in which he held Scholasticism, and indirectly for the vagaries of his own philosophy, and the ultimate shipwreck of his faith.

This is a section of Mr. Gray's recent paper read before The Philosophers' Academy covering "The Catholic Movement in France (1830-1850) and the Philosophy of de Lamennais".Complete ignorance of the system of the Medieval Schoolmen seems responsible for the contempt in which he held Scholasticism, and indirectly for the vagaries of his own philosophy, and the ultimate shipwreck of his faith.

This is a section of Mr. Gray's recent paper read before The Philosophers' Academy covering "The Catholic Movement in France (1830-1850) and the Philosophy of de Lamennais".Complete ignorance of the system of the Medieval Schoolmen seems responsible for the contempt in which he held Scholasticism, and indirectly for the vagaries of his own philosophy, and the ultimate shipwreck of his faith.

Le Socrate de Xénophon et la démocratie présente une interprétation nuancée du témoignage de Xénophon sur l’attitude de Socrate à l’endroit de la démocratie athénienne. Cette étude conteste les interprétations qui ont été trop restrictives dans le choix des témoignages et trop négatives dans leurs conclusions. Elle tient compte, d’une part, des différents paramètres qui permettent de définir la démocratie ; d’autre part, des réalités de la démocratie athénienne. Les principaux textes pertinents proviennent des Mémorables. Nous traitons de la nature (...) de cet ouvrage et de la façon dont il expose l’attitude de Socrate à l’endroit des lois et des institutions du régime démocratique, notamment l’assemblée et le tirage au sort. Cette étude présente enfin une interprétation plus nuancée de la propre attitude de Xénophon à l’endroit de la démocratie, attitude qui a elle-même influé sur la façon dont on a, par le passé, évalué l’attitude de son Socrate.Xenophon’s Socrates and Democracy offers a balanced interpretation of Xenophon’s evidence for Socrates’ attitude to the Athenian democracy, arguing against interpretations that have been too selective in their evidence and too negative in their conclusions. It takes due account of the various parameters that define democracy and the realities of Athenian democracy. The main evidence is from Memorabilia. There is discussion of nature of this work, and then of how it expresses Socrates’ attitude to the laws of the democracy and other processes such as sortition and the assembly. The paper also offers a more balanced interpretation of Xenophon’s own attitude to democracy, which has influenced past assessments of the attitude of his Socrates. (shrink)

Nicholas Agar, Jeff McMahan and Allen Buchanan have all expressed concerns about enhancing humans far outside the species-typical range. They argue radically enhanced beings will be entitled to greater and more beneficial treatment through an enhanced moral status, or a stronger claim to basic rights. I challenge these claims by first arguing that emerging technologies will likely give the enhanced direct control over their mental states. The lack of control we currently exhibit over our mental lives greatly contributes to our (...) sense of vulnerability. I then argue moral status should be viewed in terms of vulnerability. The enhanced will slowly gain the ability to command their mental states, reducing their vulnerability. These radically enhanced beings will have greater capacities, and possibly an inner life more valuable than our own. They will also be less vulnerable, and as a result, their moral status will be subordinate to our own. (shrink)

According to models of objectification, viewing someone as a body induces de-mentalization, stripping away their psychological traits. Here evidence is presented for an alternative account, where a body focus does not diminish the attribution of all mental capacities but, instead, leads perceivers to infer a different kind of mind. Drawing on the distinction in mind perception between agency and experience, it is found that focusing on someone's body reduces perceptions of agency but increases perceptions of experience. These effects were found (...) when comparing targets represented by both revealing versus nonrevealing pictures or by simply directing attention toward physical characteristics. The effect of a body focus on mind perception also influenced moral intuitions, with those represented as a body seen to be less morally responsible but more sensitive to harm. These effects suggest that a body focus does not cause objectification per se but, instead, leads to a redistribution of perceived mind. (shrink)

SAMANTHA GREY | : Prevailing connotations of reconciliation orbit concord or harmonious coexistence, meaning that concern for justice is necessarily subordinated to a more casually pragmatic peace. Bringing justice considerations to the fore means focusing on reparations as a key element of reconciliation’s suite of activities—but reparations are necessarily a matter of process, which precludes considering elements of the “package” in isolation from one another, as is the case with traditional evaluative criteria of motivation or proportion. Accordingly, this article (...) proposes that reparations are better framed as a considered reaction to the unjust allocation of burdens, so that subsequent reallocations serve justice by answering the needs and demands of survivors. Taking cues from a variety of sources both within and beyond the transitional justice literature, the work at hand attempts just such a retrospective reframing by looking at a recently completed Canadian reparations process: the Indian Residential Schools Settlement Agreement. | : Les connotations dominantes de la réconciliation gravitent autour de la concorde ou de la coexistence harmonieuse, signifiant que le souci de la justice est nécessairement subordonné à une paix plus pragmatique. Mettre les considérations de justice au premier plan implique de mettre l’accent sur les réparations comme un élément clé de la série d’activités de la réconciliation, mais les réparations sont nécessairement une question de processus, ce qui exclut de considérer ses éléments isolément, comme c’est le cas des critères évaluatifs traditionnels de motivation ou de proportion. En conséquence, cet article propose que les réparations sont mieux conçues comme une réaction réfléchie à l’attribution injuste des charges, de sorte que les réallocations ultérieures servent la justice en répondant aux besoins et aux exigences des survivants. S’inspirant d’une variété de sources à l’intérieur et à l’extérieur de la littérature sur la justice transitionnelle, le présent travail tente un tel recadrage rétrospectif en examinant un processus canadien de réparations récemment terminé : la Convention de règlement relative aux pensionnats indiens. (shrink)