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Strategies for Engineered Negligible Senescence

Strategies for Engineered Negligible Senescence

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Article
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Should we be considering the social and economic ramifications of a society where life-span could be limitless?

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Citations

... This aspiration has left noticeable marks in virtually every human culture reflecting on the possibility of transcending death [2,3]. While such an extreme wish to attain some form of immortality is still implicitly embedded into the so-called movement of "posthumanism" 1 (for a brief overview see [7]), in the biomedical science it has been transformed into a more practical aim of slowing down or potentially even reversing ageing [8][9][10][11][12], progressively reaching the "age escape velocity" 2 that will open the prospect of extreme human life extension [14]. ...
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BACKGROUND: There is a growing consensus that chronological age (CA) is not an accurate indicator of the ageing progress and that biological age (BA) instead is a better measure of an individual's risk of age-related outcomes and a more accurate predictor of mortality than actual CA. In this context BA measures the "true" age that is an integrated result of an individual's level of damage accumulation across all levels of biological organization, along with preserved resources. The BA is plastic and depends upon epigenetics. Brain state is an important factor contributing to health-and lifespan. METHODS AND OBJECTIVE: Quantitative electroencephalography (qEEG) derived brain BA (BBA) is a suitable and promising measure of brain ageing. In the present study we aimed to show that BBA can be decelerated or even reversed in humans (N = 89) by using customized programs of nutraceutical compounds or lifestyle changes (Mean duration = 13 months). RESULTS: We observed that the BBA was younger than CA in both groups at the end of the intervention. Further, the BBA of participants in the nutraceuticals group was 2.83 years younger at the endpoint of the intervention compared with BBA score at the beginning of the intervention, while the participants' BBA of the lifestyle group scored only 0.02 years younger at the end of the intervention. These results were accompanied by improvement in mental-physical health comorbidities in both groups. Pre-intervention BBA score, as well as sex of participants were considered as confounding factors and analyzed separately. CONCLUSIONS: Overall, the obtained results support the feasibility of the goal of this study and also provide the first robust evidence that halting and reversal of brain ageing is possible in humans within a reasonable (practical) timeframe of around one year.
... De Grey glaubt, man müsse nur lange genug überleben, um schließlich am Ende in den Genuss der revolutionären Methoden der vollständigen Alternsprävention zu gelangen, von denen De Grey glaubt, sie werden für bereits jetzt geborene Menschen verfügbar sein (vgl. De Grey 2004). Es liegt auf der Hand, dass hier keine Kombination von Alternsprävention mit Morbiditätskompression gesucht wird, sondern es zunächst darum geht, vor allem das Leben zu verlängern, und zwar mit allen medizinischen Methoden, die zur Verfügung stehen. ...
Chapter
Alternsprävention mit Hilfe von biotechnologischen Eingriffen ist der Biologie des Alterns oder Biogerontologie bereits im Laborversuch bei unterschiedlichen Organismen gelungen. Durch die Manipulation einzelner Gene, durch die sogenannte Kalorienrestriktion, d. h. einem Labortier werden nur 70 % der Kalorien zur Verfügung gestellt, die es sonst zu sich nehmen würde, und durch Pharmazeutika wurde die Lebensspanne von Labororganismen wie Nematoden oder Hefen bis zu zehnfach verlängert. Vergleichbare Eingriffe sollen ebenfalls beim Menschen möglich sein, was speziesübergreifende, ähnliche Mechanismen der Alterung nahelegen (vgl. Fontana/Partridge/Longo 2010).
... In some cases, historical debates about the desired length of life have been assimilated in the accounts of bio-conservatives such as Kass and Sandel, who oppose life-extension because of the challenges they pose to human self-understanding and virtue (Kass 1983;Sandel 2004). These are typically in conflict with bio-progressive transhumanists like Nik Bostrom and Aubrey de Grey who seek an end to ageing and death (Bostrom 2005;De Grey 2004). This modern debate has become further complicated by the jockeying of rival research factions for research funding for anti-ageing interventions (Breitenbach et al. 2006;Warner et al. 2005). ...
Article
Drawing on Ezekiel Emanuel’s controversial piece ‘Why I hope to die at 75,’ I distinguish two types of concern in ethical debates about extending the human lifespan. The first focusses on the value of living longer from prudential and social perspectives. The second type of concern, which has received less attention, focusses on the value of aiming for longer life. This distinction, which is overlooked in the ethical literature on life extension, is significant because there are features of human psychology and the structure of a life that should give pause when considering how long one should aim to live, but which do not neatly coincide with considerations about how valuable additional life is likely to be. I argue that, while Emanuel’s case for hoping to die at 75 is unconvincing, he nonetheless provides weak pro tanto considerations in favour of taking a moderate life span as a prudential aim around which to base at least some significant life plans.
... There are two other mathematically based predictions of radical life extension that are similar to the one stated earlier. In one case, de Grey (15) contends that humans are approaching an "actuarial escape velocity"-a hypothetical world in which "mortality rates fall so fast that people's remaining (not merely total) life expectancy increases with time." For this to happen, medical technology would need to manufacture survival time faster than the rate of living is taking it away-a condition de Grey contends (without evidence) is forthcoming. ...
Article
The rise in human longevity is one of humanity’s crowning achievements. While advances in public health beginning in the 19th century initiated the rise in life expectancy, recent gains have been achieved by reducing death rates at middle and older ages. A debate about the future course of life expectancy has been ongoing for the last quarter century. Some suggest that historical trends in longevity will continue and radical life extension is either visible on the near horizon or it has already arrived; while others suggest there are biologically based limits to duration of life, and those limits are being approached now. In “inconvenient truths about human longevity” we lay out the line of reasoning and evidence for why there are limits to human longevity; why predictions of radical life extension are unlikely to be forthcoming; why health extension should supplant life extension as the primary goal of medicine and public health; and why promoting advances in aging biology may allow humanity to break through biological barriers that influence both lifespan and healthspan, allowing for a welcome extension of the period of healthy life, a compression of morbidity, but only a marginal further increase in life expectancy.
... There are even scientists who believe in the possible realization of longevity escape velocity. In this scenario death rates fall so fast that people's remaining life expectancy increases with time because therapies restore health faster than the rate of body deterioration due to biological ageing (De Grey (2004)). ...
... Furthermore, striving to increase our longevity, with the goal of at least some transhumanists that we achieve near or actual immortality (de Grey, 2004), could lead to a "tedious" existence as Bernard Williams (1973) forewarns. 12 Over an extended period of existence-even if not an infinitely extended period-Williams contends that we would eventually cease to value those goods which we initially sought immortality to enjoy. ...
Chapter
I approach the subject of human enhancement—whether by genetic, pharmacological, or technological means—from the perspective of Thomistic/Aristotelian philosophical anthropology, natural law theory, and virtue ethics. Far from advocating a restricted or monolithic conception of “human nature” from this perspective, I outline a set of broadly-construed, fundamental features of the nature of human persons that coheres with a variety of historical and contemporary philosophical viewpoints. These features include self-conscious awareness, capacity for intellective thought, volitionalautonomy, desire for pleasurable experiences, and the necessity of healthy biological functioning. On this basis, I contend that there may be legitimate forms of human enhancement for specific purposes related to the physical, cognitive, and emotive dimensions of human existence. However, wider philosophical considerations call into question whether societal attitudes towards enhancement and the differences that may emerge between those who are enhanced versus the unenhanced may raise insurmountable questions of justice, as well as a loss of virtues associated with what Alasdair MacIntyre refers to as our “acknowledged dependency.” This presentation will navigate towards conclusions differentiating principled from practical objections to specific forms of, and means towards achieving, enhancement of certain human capacities. While critical of some forms of human enhancement, I nevertheless argue that other forms of enhancement are, in principle, morally permissible—and for which any practical concerns may be surmountable—insofar as they positively support human flourishing according to our nature as living, sentient, social, and rational animals.
... Opinions diverge (e.g., (Aledo and Blanco, 2015; Anton et al., 2005; Baars, 2012; Caplan, 2005; de Magalhaes, 2014; de Magalhães, 2013; Vijg and de Grey, 2014)), and commonly described fears include concerns about overpopulation and inequality, economic collapse due to healthcare and the idea that aging is natural and should not be tampered with (de Magalhaes, 2014; de Magalhães, 2013). Advocates of life-extension research state that curing aging is not scientifically implausible and we may soon reach the " longevity escape velocity " (de Grey, 2004), a stage of medical progress that will result in delaying aging-related degeneration and death to such an extent that there is time to carry out research seeking more effective therapies later on (Vijg and de Grey, 2014) and dispute the alarms raised by others by noting the failed predictions of Malthus regarding the disasters due to overpopulation (Sethe and de Magalhães, 2013; Trewavas, 2002). No matter where one stands in respect to the pursuit of an increasingly longer life, there is no disagreement about the necessity of fighting age-related illnesses and comorbidities (Longo et al., 2015). ...
Article
Answering the question as to why we age is tantamount to answering the question of what is life itself. There are countless theories as to why and how we age, but, until recently, the very definition of aging - senescence - was still uncertain. Here, we summarize the main views of the different models of senescence, with a special emphasis on the biochemical processes that accompany aging. Though inherently complex, aging is characterized by numerous changes that take place at different levels of the biological hierarchy. We therefore explore some of the most relevant changes that take place during aging and, finally, we overview the current status of emergent aging therapies and what the future holds for this field of research. From this multi-dimensional approach, it becomes clear that an integrative approach that couples aging research with systems biology, capable of providing novel insights into how and why we age, is necessary.
... Our study reinforces biological forecasts [169,345,349] contrasting with extension claims [350][351][352]. However our period of observation is restricted, and the size of the population studied is relatively small. ...
... However, this scenario defended by prolongevists, seems to be possible only if nutritional, climatic, social or economic conditions continuously improve. Important medical and technological advances may also lead to life extension [352], but major health determinants already contribute to reduce life expectancy progression in developed countries [354,355]. In addition, the current tendency in world climate change and environmental resources degradation may result in adverse health consequences especially affecting the eldest individuals [356]. ...
Thesis
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Background and objectives: along their careers, elite athletes are subjected to specific constraints that distinguish them from the general population. Such constraints, related to the high intensity of their physical activity, their overexposure to injuries or particular lifestyle, may have long-term consequences on the athletes' health, and ultimately on their longevity. Thus, the main goals of the present study are the following: 1) to describe and analyze elite athletes’ longevity and specific causes of mortality in comparison with the general population and according to the type of effort they performed; and 2) to investigate their lifespan trends in comparison with the longest-lived humans in order to apprehend the current scenario of human longevity trends. Methods: we collected data on the biography and the athletic performances of all the French athletes who participated in the Olympic Games (OG) from 1912 to 2012 (n = 4708), and all the French cyclists who participated in the Tour de France (TDF) from 1947 to 2012 (n=786). Then, we verified their vital statuses through the National Registry of Identification of Physical Persons (RNIPP). For the deceased athletes, we obtained the causes of their deaths through the Centre for epidemiology on medical causes of death (CépiDc). We compared the athletes’ overall and specific mortality (according to the main chapters of the International Classification of Disease) with the French civilian life tables using Standardized Mortality Ratio (SMR) and the Kaplan-Meier methods. We adapted and applied the life years-lost method under the competing risk model to quantify differences on longevity due to major causes of death according to the athletes’ type of effort. Furthermore, we collected data on worldwide deceased Olympians participating in the OG from 1896 to 2012 (n=19 012) and on worldwide supercentenarians (>110 years) deceased between 1900 and 2013 (n= 1 205) in order to analyze their lifespan trends using a density analysis tool (total number of life durations per birth date). Findings and conclusion: French elite athletes show consistently lower mortality (≈40-50% lower) in comparison with their compatriots, whether female or male Olympians, or professional cyclists, mostly related with a lower cardiovascular (≈ 40-60% lower) and cancer mortality (≈ 45% lower). No excess mortality was observed in elite athletes for any of the specific causes of death we studied. French Olympians’ lower mortality results in an average of seven years of life saved in relation to the general population. This gain partitioned according to specific causes of deaths shows that cardiovascular longevity benefit is associated with the type of sports practiced during the Olympic career, favoring combined type of effort over very short- or very long-duration effort. In relation to cancer mortality, all types of effort studied were associated with better longevity. Despite their survival advantage, no Olympian in the world, up to date, has ever reached the status of a supercentenarian, as the longest-lived was 106 years old. The common lifespan trends between Olympians and supercentenarians indicate similar mortality pressures over both populations that increase with age, a scenario that is better explained by a biological “barrier” limiting further progression. The supercentenarians’ density trends show a current stagnation of the human longevity.
... Ord 2006, Harris 2007;Levy 2007); physical enhancements, such as doping in sport (Savulescu et al. 2004); moral enhancement by modulating moral emotions or dispositions such as empathy or aggressiveness (Douglas 2008, Persson and Savulescu 2012, Douglas 2013, Kahane and Savulescu 2013; love enhancement through biochemical modulation of lust, attraction and attachment (Savulescu and Sandberg 2008;Earp et al 2013;Earp et al 2015); and increases to healthy human lifespan (e.g. Bostrom 2005a, de Grey 2004. ...
Article
Ethical debate surrounding human enhancement, especially by biotechnological means, has burgeoned since the turn of the century. Issues discussed include whether specific types of enhancement are permissible or even obligatory, whether they are likely to produce a net good for individuals and for society, and whether there is something intrinsically wrong in playing God with human nature. We characterize the main camps on the issue, identifying 3 main positions: permissive, restrictive and conservative positions. We present the major sub-debates and lines of argument from each camp. The review also gives a flavour of the general approach of key writers in the literature such as Julian Savulescu, Nick Bostrom, Michael Sandel and Leon Kass.
... Our study reinforces biologic forecasts (10,25,29) contrasting with extension claims (7,30,31). However, our period of observation is restricted, and the size of the population studied is relatively small. ...
Article
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Life-span trends progression has worldwide practical implications as it may affect the sustainability of modern societies. We aimed to describe the secular life-span trends of populations with a propensity to live longer—Olympians and supercentenarians—under two hypotheses: an ongoing life-span extension versus a biologic “probabilistic barrier” limiting further progression. In a study of life-span densities (total number of life durations per birth date), we analyzed 19,012 Olympians and 1,205 supercentenarians deceased between 1900 and 2013. Among most Olympians, we observed a trend toward increased life duration. This trend, however, decelerates at advanced ages leveling off with the upper values with a perennial gap between Olympians and supercentenarians during the whole observation period. Similar tendencies are observed among supercentenarians, and over the last years, a plateau attests to a stable longevity pattern among the longest-lived humans. The common trends between Olympians and supercentenarians indicate similar mortality pressures over both populations that increase with age, scenario better explained by a biologic “barrier” forecast.