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Strategies for Engineered Negligible Senescence
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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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I denna rapport har en kartläggning genomfö...
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... Category theory is the "mathematics of mathematics" investigating the structure and relationships between different types of mathematical objects (e.g. sets, groups, vector spaces) using the concept of categories and functions between them, composing their relations, now seen in the AI infrastructure (de Haan et al. 2020), information theory (Katsumata et al. 2023) and genomics (Wu 2023). Since category theory can generalize formal connections between seemingly diverse domains, it has been hypothesized as an appropriate mathematics for treating the systems, states, and processes of biology by focusing on dynamic relationships and interactions (Rosen 1991). ...
... The biggest risk in the AI Health Agents proposal is that although technology development is proceeding quickly, the implementation of healthy longevity programs may be too late to adequately respond to aging demographics. Longevity scholars therefore promote the "escape velocity" idea of deploying immediate interventions to buy enough time until more complete solutions are available (de Grey 2004). Although a contemporary lens sees longevity as a technology, it may not be easy to reprogram biology. ...
Health Agents are introduced as the concept of a personalized AI health advisor overlay for continuous health monitoring (e.g. 1000x/minute) medical-grade smartwatches and wearables for "healthcare by app" instead of "sickcare by appointment." Individuals can customize the level of detail in the information they view. Health Agents "speak" natural language to humans and formal language to the computational infrastructure, possibly outputting the mathematics of personalized homeostatic health as part of their reinforcement learning agent behavior. As an AI health interface, the agent facilitates the management of precision medicine as a service. Healthy longevity is a high-profile area characterized by the increasing acceptance of medical intervention, longevity biotech venture capital investment, and global priority as 2 billion people will be over 65 in 2050. Aging hallmarks, biomarkers, and clocks provide a quantitative measure for intervention. Some of the leading interventions include metformin, rapamycin, spermidine, NAD+/sirtuins, alpha-ketoglutarate, and taurine. AI-driven digital biology, longevity medicine, and Web3 personalized healthcare come together in the idea of Health Agents. This Web3 genAI tool for automated health management, specifically via digital-biological twins and pathway2vec approaches, demonstrates human-AI intelligence amplification and works towards healthy longevity for global well-being. The AI Longevity Mindset The AI Mindset The AI Stack. The AI infrastructure is evolving rapidly, particularly with genAI (generative AI which creates new data based on what it has learned from a training dataset). Activity can be ordered in the four tiers of human-interface AI assistants, reinforcement learning (RL) agents (self-driving, robotics), knowledge graphs, and artificial neural network architectures (ANNs). AI assistants and RL agents (embodied through prompting) are an intelligence amplification tool for human-AI collaborative access to the other tiers of the vast range of knowledge and computational power now available. ANNs. The first neural network architecture to deliver genAI at scale is transformers (GPTs, generative pretrained transformer neural networks), Large Language Models (LLMs) which use attention as the mechanism to process all connections in a dataset simultaneously to perform next word (any token) prediction (OpenAI 2023). LLMs treat a data corpus as a language, with syntax, semantics, and grammar, whether natural language, mathematics, computer code, or proteins. These kinds of Foundation Models are trained on broad internet-scale data for application to a wide range of use cases. Transformers are so-called because they "transform" vector-based data representations during the learning phase (using linear algebra methods). Transformer architectures are being extended with state-of-the-art LLMs released for multimodal VLMs (vision-language models) (Gemini 2023), larger context windows (e.g. genome-scale training, 1 million base pair size context window (HyenaDNA, Nguyen et al. 2023)), and longer sequential data processing with various convolutional and other methods such as SSMs (structured state space models (Mamba, Gu and Dao, 2023)) and model grafting (hybrid network architectures evolving during training, StripedHyena-7b (7 billion parameters (learned weights between data elements), Poli et al. 2023). GPTs to GNNs: 2D to 3D+. An advance in digital biology is GNNs (graph neural networks, technically a form of transformer) to process 3D data such as molecules (Bronstein et al. 2021) with attention or message-passing. The early success of GPTs is credited to the "traditional" machine learning recipe (Halevy et al. 2009) of a small set of algorithms operating on a very large dataset, with substantial computational power. GNNs require a more extensive implementation of physics to treat 3D environments. The transformations of data representations in GNNs are more closely tied to the three main symmetry transformations in physics: translation (displacement), rotation, and reflection.
... 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 in the so-called movement of "posthumanism" (posthumanism seeks to improve human nature by using technology to transcend the limitations of the body and mind [4][5][6]) (for a brief overview, see [7]), in biomedical science it has been transformed into a more practical aim of slowing down or potentially even reversing aging [8][9][10][11][12], progressively reaching the "age escape velocity" (such an approach presupposes that death could be interactively delayed by anticipating and fixing the damaging effects of aging across the lifespan [13]), which will open the prospect of extreme human life extension [14]. ...
Background:
There is a growing consensus that chronological age (CA) is not an accurate indicator of the aging process 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, which 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 aging. 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 BBA was younger than CA in both groups at the end of the intervention. Furthermore, the BBA of the participants in the nutraceuticals group was 2.83 years younger at the endpoint of the intervention compared with their BBA score at the beginning of the intervention, while the BBA of the participants in the lifestyle group was only 0.02 years younger at the end of the intervention. These results were accompanied by improvements in mental-physical health comorbidities in both groups. The pre-intervention BBA score and the sex of the participants were considered 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 aging are possible in humans within a reasonable (practical) timeframe of approximately one year.
... Ethics is not just agency, but recognition [25]. As far as I know, this key question has hardly been addressed, and when it has been touched upon it has been only tangentially and in a secondary way. 2 But before entering fully into the question of whether robots can come to 2 There has been a recent debate on the so-called "electronic personhood" in the European Parliament [14], Prodhan, [39]). But I consider that this approach to personhood differs completely from what is raised here. ...
This article attempts to answer the question of whether robots can have personal identity. In recent years, and due to the numerous and rapid technological advances, the discussion around the ethical implications of Artificial Intelligence, Artificial Agents or simply Robots, has gained great importance. However, this reflection has almost always focused on problems such as the moral status of these robots, their rights, their capabilities or the qualities that these robots should have to support such status or rights. In this paper I want to address a question that has been much less analyzed but which I consider crucial to this discussion on robot ethics: the possibility, or not, that robots have or will one day have personal identity. The importance of this question has to do with the role we normally assign to personal identity as central to morality. After posing the problem and exposing this relationship between identity and morality, I will engage in a discussion with the recent literature on personal identity by showing in what sense one could speak of personal identity in beings such as robots. This is followed by a discussion of some key texts in robot ethics that have touched on this problem, finally addressing some implications and possible objections. I finally give the tentative answer that robots could potentially have personal identity, given other cases and what we empirically know about robots and their foreseeable future.
... 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]. ...
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. ...
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). ...
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. ...
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)). ...
... The second category involves the ethical implications of technologies directed at altering the ageing process by the modes of slowing, 35 preventing, 36 37 reversing 38 or even escaping ageing. 39 Which, if any, of these modes can be considered justified given the aforementioned proageing challenges of bioconservatives such as Kass? Which types of technologies are likely to result in increased healthspan along with increased lifespan, and, as an ageing person, do I have a right to such technologies as a corollary to rights to life and health? ...
Applied ethics is home to numerous productive subfields such as procreative ethics, intergenerational ethics and environmental ethics. By contrast, there is far less ethical work on ageing, and there is no boundary work that attempts to set the scope for ‘ageing ethics’ or the ‘ethics of ageing’. Yet ageing is a fundamental aspect of life; arguably even more fundamental and ubiquitous than procreation. To remedy this situation, I examine conceptions of what the ethics of ageing might mean and argue that these conceptions fail to capture the requirements of the desired subfield. The key reasons for this are, first, that they view ageing as something that happens only when one is old, thereby ignoring the fact that ageing is a process to which we are all subject, and second that the ageing person is treated as an object in ethical discourse rather than as its subject. In response to these shortcomings I put forward a better conception, one which places the ageing person at the centre of ethical analysis, has relevance not just for the elderly and provides a rich yet workable scope. While clarifying and justifying the conceptual boundaries of the subfield, the proposed scope pleasingly broadens the ethics of ageing beyond common negative associations with ageing.
... 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. ...
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.
