Personalist Bioethics as a Guide to Assessing Emerging Anti-aging Therapies

Abstract

Over the last several years, the idea that aging is inevitable has been replaced by scientific evidence showing that it is rather a malleable process. In this article, the most relevant and promising therapies have been classified into three large groups, based on their possible bioethical implications: (1) nutritional interventions, (2) pharmacological interventions, and (3) gene therapies. After defining the mechanisms of action of each group of treatments, as well as the risks and benefits currently identified, we evaluated each group following guidelines for the ethical assessment of interventions on the human body. These are based on the principles of personalist bioethics, which has allowed us to discern the licitness of such practices. After performing the analysis, we concluded that, at present, only nutritional interventions can be considered acceptable as anti-aging therapies. Drugs and gene therapies are still at too early a stage of development and their application would endanger human life. Finally, some recommendations are proposed in the field of aging founded on health care, based on healthy dietary control that, in turn, allows us to embrace the frailty and weakness of human nature, which become more evident during old age.

Introduction

The quest for immortality, eternal youth, and good health has long fascinated humanity. What was once the realm of fantasy in literature and film is now an area of active scientific research. Today, numerous researchers and private companies are working to understand aging and extend healthy human life (de Magalhães, Stevens and Thornton 2017). A significant shift in aging research is the emerging strategy of treating aging itself, rather than simply managing age-related diseases. This approach, known as geroscience, frames aging as a treatable condition. The World Health Organization reflects this change by including “ageing-associated decline in intrinsic capacity” in the international classification of diseases 11th revision under code MG2A (The Lancet Diabetes & Endocrinology 2018).

While delaying chronic diseases and extending life may seem promising, these advancements also raise profound moral, social, and economic concerns. Scholars emphasize the need for rigorous ethical reflection on such interventions (Ros and Carrascosa 2020). Beyond the clinical and technical questions, a powerful new ethos is emerging—one that regards aging and death as failures to be eradicated and human life as a project of endless optimization. This emerging ethos is deeply rooted in utilitarian and technocratic values that prioritize control, efficiency, and productivity, often at the expense of a holistic understanding of the human person.

This article argues that the personalist bioethical framework offers a coherent and ethically grounded foundation for evaluating anti-aging interventions, as it centers on the dignity, integrity, and identity of the human person. Rooted in the Aristotelian–Thomistic tradition, personalism sees the individual as an integrated being—physical, psychological, spiritual, and social (Sgreccia 2012). Unlike utilitarian or relativist approaches, personalism upholds a consistent anthropology that treats each person as a subject of moral worth, not a means to an end. Building on this foundation, we apply the Guidelines for the Ethical Assessment of Interventions on the Human Body in View of the Emergence of NBIC Technologies for Enhancement, developed from a personalist bioethical perspective, to assess anti-aging techniques and propose ethically grounded recommendations that safeguard human dignity.

The Aging Process and Its Biomarkers

From a biological point of view, aging can be defined as the progressive deterioration of the functional and physiological capacities of living beings associated with the passage of time, resulting from the accumulation of different molecular and cellular damage and ultimately leading to death (Alle et al. 2021; Lagoumtzi and Chondrogianni 2021; Liang and Wang 2018; López-Otín et al. 2023). It is the greatest risk factor for age-related diseases (de Lima Camillo and Quinlan 2021; Kulkarni et al. 2022; Mahmoudi, Xu and Brunet 2019; McHugh and Gil 2018). Despite the numerous advances made in the study and understanding of aging in recent years, even now, it is still a complex biological process with multiple questions for science (Campisi et al. 2019; de Lima Camillo and Quinlan 2021; Ros and Carrascosa 2020).

It has recently been shown that the aging process is a plastic process that can be controlled by different strategies in such a way that, ultimately, aging can be postponed and even prevented or reversed. Geroscience provides a new approach to treating age-related diseases. It is based on the idea of anticipating the consequences of aging (Kulkarni et al. 2022) by directing therapies against the aging process itself, to prevent the body from growing old, thereby simultaneously improving or preventing various age-related diseases. Specifically, geroscience treatments will act on metabolic pathways that modulate longevity, as these are the same pathways involved in the development of numerous age-related diseases (Campisi et al. 2019).

Twelve biomarkers have recently been defined that are present in all aging processes, the presence of which exacerbates the process. Together, they determine the aging phenotype (López-Otín et al. 2023). Moreover, by properly treating one or several of these 12 signs, it could be possible to delay the onset of old age or slow down its development until it is stopped or even reversed. Current research lines that seek to reverse or overcome aging are aimed at one or more of these hallmarks. These 12 identifiers are closely interconnected; they do not act independently, but the presence of one of them in the body may trigger the activation of another. Similarly, therapy targeting a single biomarker can affect others (López-Otín et al. 2023). These biomarkers can be classified into three hierarchical categories: (1) primary: those that are considered the main causes of cell damage; (2) antagonistic: those considered part of compensatory or antagonistic responses to damage, which initially mitigate it, but over time, if chronic or exacerbated, become deleterious themselves; and (3) integrative: those that directly affect homeostasis and tissue function and are the final result of the two previous groups. Ultimately, they are responsible for the overall age-related functional decline (López-Otín et al. 2023). The 12 hallmarks of aging are:

1. Genomic instability. DNA is constantly subjected to factors, both external and internal, that threaten its integrity and stability. These include chemical agents, DNA replication errors and reactive oxygen species (ROS), among others, which ultimately cause cellular malfunction that furthers the deterioration of tissues and organs. Different processes and repair mechanisms in the body correct this damage, but they are not perfect and lose effectiveness with age (López-Otín et al. 2023).

2. Telomere attrition. The progressive and cumulative loss of telomere-protective sequences is age-related, a factor that can be modulated by telomerase activation (López-Otín et al. 2023).

3. Epigenetic alterations. The act of faithful DNA repair advances aging due to relocation of chromatin factors, which causes the erosion of the epigenetic landscape, cellular exdifferentiation, senescence, and advancement of the DNA methylation clock, which can be reversed using Yamanaka factors Oct4, Sox2, and Klf4 (de Lima Camillo and Quinlan 2021; López-Otín et al. 2023; Yang et al. 2023).

4. Loss of proteostasis. As cells age, environmental stress accumulates and the mechanisms responsible for maintaining the correct protein composition become less efficient, causing an increase in the proportion of toxic proteins in the body (López-Otín et al. 2023).

5. Disabled macroautophagy. There is strong evidence demonstrating that the age-related decline in autophagy constitutes one of the most important mechanisms of reduced organelle turnover, leading to an increasingly inefficient degradation process that likely contributes to the accumulation of protein aggregates and dysfunctional organelles, reduced elimination of pathogens, and enhanced inflammation (López-Otín et al. 2023).

6. Deregulated nutrient sensing. When nutrients are in short supply, the metabolism adapts to focus on cell maintenance and repair. Based on this finding, three types of anti-aging strategies founded on the inhibition of nutrient abundance signaling are being designed: reducing food; drugs such as rapamycin that fool the body into believing that there are fewer nutrients available; and inhibiting signals from insulin or its close relative, insulin-like growth factor (López-Otín et al. 2023).

7. Mitochondrial dysfunction. Aging is associated with a progressive deterioration in mitochondrial function. The main role of ROS, which are produced mainly during the cellular respiration process, is to act as signaling molecules of cellular stress, which mediate the activation of compensatory homeostatic responses beneficial to the body. However, the gradual mitochondrial dysfunction that occurs with age results in excessive production of ROS, which cause cell damage (Campisi et al. 2019; de Lima Camillo and Quinlan 2021; López-Otín et al. 2023).

8. Cellular senescence. Cellular senescence is a response to cellular damage that contributes to repair of damaged tissues and tumor suppression (Di Micco et al. 2021; Kowald, Passos and Kirkwood 2020; López-Otín et al. 2023). However, it becomes deleterious and accelerates aging by weakening the regenerative capacity of tissues and the immune system to eliminate them once the damage is repaired (immunosenescence), resulting in a situation of latent and chronic inflammation known as inflammaging (Kowald, Passos and Kirkwood 2020; López-Otín et al. 2023; McHugh and Gil 2018; Neves and Sousa-Victor 2020; Santoro et al. 2020; Tchkonia, Palmer and Kirkland 2021). It can also trigger other types of damage, including oncogenic signaling, genotoxic damage, critically short telomeres, mitochondrial damage, viral or bacterial infection, oxidative damage, nutrient imbalance, and mechanical stress (López-Otín et al. 2023).

9. Stem cell exhaustion. As the body ages, the accumulation of DNA lesions or telomere shortening, among other damage, causes the degeneration of stem cells, which decreases the regenerative capacity of tissues (López-Otín et al. 2023; Wang et al. 2019; Zhu et al. 2021).

10. Altered intercellular communication. It has been observed that the changes that a tissue undergoes as a result of aging can induce the transformation of other tissues, deteriorating them (Campisi et al. 2019; López-Otín et al. 2023; Santoro et al. 2020).

11. Chronic inflammation. In association with enhanced inflammation during aging (“inflammaging”), immune function declines. Although systemic inflammation is mechanistically linked to all the aforementioned age-associated changes, inflammation constitutes a hallmark on its own. Indeed, specific therapies targeting the inflammatory and immune system can accelerate or decelerate the aging process across different organ systems (López-Otín et al. 2023).

12. Dysbiosis. In recent years, the gut microbiome has emerged as a key factor in the aging process, as it has an important impact on several physiological processes like protection against pathogens, production of vitamins or nutrient digestion, among others. Well-known microbial metabolites are involved in immune regulation, inflammation, and aging. Different therapies targeting gut microbiota are being studied, most notably fecal microbiota transplantation (López-Otín et al. 2023).

Personalist Guidelines for the Ethical Assessment of Interventions on the Human Body

The great novelty of personalist philosophy is that it puts the person at the center of all its anthropological argumentation. It establishes a paradigm shift in the ontological foundation, based on the philosophical consideration of the person as a who and not a what, since man is not a thing, but a subject essentially different from other living beings, individual and unique, possessing an inherent dignity. This individual-centered philosophical perspective seeks to transcend the positions of certain modern thinkers, such as Descartes, Husserl, and Nietzsche, who failed to grasp the singular essence of the person and its dual dimensions: uniqueness and universality. Furthermore, these thinkers omitted the crucial aspect that is only revealed when each woman and man are evaluated individually: the existence of an ultimate, irreducible, and unrepeatable dimension that transforms each human being into a unique “who,” which, in a full sense, defines what it means to be a person. The process of grasping the singular reality that constitutes the person has been long and complicated; in fact, it was only in the twentieth century that a full philosophical awareness of this singularity was achieved and an effort was made to find terms to describe this phenomenon. In this context, personalist philosophy is especially significant because it brings together the attempts oriented in this direction. Thus, the anonymous individual of the enlightenment was transformed into a personal self that managed to integrate into its structure an essential community with other human beings, as well as a difference so profound that it allows us to affirm that each human being, is, in some way, unique in their own right (Gómez n.d.). Additionally, the greatest value is given to the voluntary dimension, that is, to freedom and love. It understands interpersonal relationships as something essential that defines man (Velasco and Manuel 2013).

Personalist bioethics, unlike other bioethical frameworks, considers it essential to have a philosophical anthropology as a frame of reference when assigning ethical value to elements such as bodily life, procreation, or death. This proposal is distinguished by the safeguarding of the fundamental good: physical life and its integrity. Personalism assumes that every human being is a person, and it is constructed with the stated objective of defending the dignity of every person. Unlike other bioethical schools of thought, the value of human life is not subject to the qualities or aptitudes of each individual but is valuable in itself from the moment of conception to the last second (Palazzani 1993).

In order to bring personalist bioethics to the practical level, Sgreccia (2012) proposes four principles applicable to medical interventions on humans. These principles are as follows:

• The principle of defense of physical life. Physical life is the fundamental value of the person since it is the basis of all other values and principles, which cannot occur without life. The body is coessential to the person.

• The principle of totality or the therapeutic principle. Any intervention carried out on human life must contemplate the patient as a whole, taking into account not only his physical good but also his spiritual and moral good. This principle requires four conditions: (i) intervention on the direct cause of the damage, (ii) that there is no less invasive alternative, (iii) a high probability of success, and (iv) consent of the patient or the person responsible for them.

• The principle of freedom and responsibility. Freedom must mean taking responsibility for one's own life first and foremost, as well as the lives of others.

• The principle of sociability and subsidiarity. This principle consists of the promotion of the life and health of society through the promotion of the life and health of each individual person, as well as the duty of the community to provide more help to those who need it most.

Based on these principles proposed by Sgreccia, guidelines for the ethical assessment of interventions on the human body have recently been developed, especially in view of the emergence of NBIC technologies for enhancement purposes, in response to the current lack of specification of ethical criteria to assess these types of interventions. These guidelines allow the interventions to be individually analyzed and contextualized, by virtue of the overall good of the persons and respect for their inalienable dignity.

More specifically, these guidelines consist of a journey through the principles of personalist bioethics in order to discern whether or not a specific technique violates them. With these guidelines, the procedure to be followed to assess the legitimacy of the use of a given enhancement technique will be to begin by answering some questions as a proposed starting point (P0), which serve to contextualize the decision well: what exactly the technique consists of, what it implies, whether there are alternatives, and so forth. Next, the questions relating to bioethical principles will be addressed by answering in a binary manner (yes/no). The details of the questions can be seen in Table 1.

Table 1.

Guidelines for the Ethical Assessment of Interventions on the Human Body.

Starting point. Questions proposed as a starting point for personal reflection on a given intervention on the human body
Q0.1. What is the specific action you are considering taking?
Q0.2. What is the purpose or objective of the intervention?
Q0.3. What are the alternatives available to get the results you expect?
Q0.4. What is the scientific evidence on the effectiveness of the technique?
Q0.5. What risks or unintended consequences does the action entail? (Consider side effects, aesthetic impact, impact on social relationships, etc.).
Q0.6. Have you lived, so far, in clearly inferior conditions in any aspect as a result of not having undergone the procedure being proposed? (Assess the difference it would make).
Q0.7. What would the impact on society and the environment be if use of the technique became widespread or generalized?
Q0.8. What is the legal status of the procedure in your country? And in the rest of the world?
Q0.9. What is the financial cost of the technique at present? Is it publicly funded? Will you need to make recurring payments later?
Q0.10. What sectors of the world's population currently have access to the technique?
First principle. Questions to evaluate whether the technique violates the principle of defense of physical human life.
Q1.1. Will the intervention endanger your life or that of another human being?
Q1.2. Has it originated from illicit practices with respect to the value of human life?
Q1.3. Are the risks to your physical, mental, or spiritual health greater than the benefits? (Assess whether the technique has been correlated with the onset of any disease or disorder, or if it is an experimental intervention).
If the answer to questions Q1.1, Q1.2, and Q1.3 is “no,” please go to the second principle.
If the answer to questions Q1.1, Q1.2, and/or Q1.3 is “yes,” you will need to assess two additional questions (Q1.4–Q1.5).
Q1.4. Is it an intervention to save life or significantly improve a seriously impaired state of health, even if it carries risks?
Q1.5. Is there a consensus from a medical professional perspective to conclude that it is the solution with the best prognosis with respect to the preservation of life and health, among all possible alternatives, including that of not performing any intervention?
If the answer to questions Q1.4 and/or Q1.5 is “no,” the technique is not considered acceptable.
If the answer to questions Q1.4 and Q1.5 is “yes,” the technique shall be considered temporarily acceptable. However, seeking a more ethical and safer alternative means to obtain the desired results should be encouraged.

Depending on the answers given to the questions, these guidelines will indicate whether to continue evaluating other criteria or principles or whether there has already been reached a temporary or definitive conclusion of acceptability or rejection of the use of the technique. This progression through the different principles according to the answers to the questions is summarized in the diagram of Figure 1.

Figure 1.

Summary Diagram of Practical Guidelines to Aid in Decision-making with Respect to Interventions on the Human Body.

Evaluation of Anti-aging Therapies Using the Guidelines for the Ethical Assessment of Interventions on the Human Body

Anti-aging therapies have been classified into three groups based on their bioethical implications: (1) nutritional interventions, (2) pharmacological interventions, and (3) gene therapy. It is important to mention that the interventions analyzed here are not all those that have been proposed as anti-aging therapies; rather, those that have greater relevance have been selected for having been more studied and considered and for being the most promising in the eyes of the scientific community specialized in this field. The three types of interventions are then outlined by answering the Q0 questions proposed in the guidelines.

Nutritional Interventions: Caloric Restriction (CR)

 Q0.1. Description. CR involves following a diet based on a limited calorie intake. CR without malnutrition is the most extensively studied nonpharmacological, nongenetic intervention that has been shown to improve health and extend life in several experimental models, such as yeasts, worms, flies, mice, and nonhuman primates (Campisi et al. 2019; Dorling, Martin and Redman 2020; Li et al. 2021; Liang and Wang 2018; Longo and Anderson 2022; López-Otín et al. 2023; Qian and Liu 2018; Ros and Carrascosa 2020). There are also other types of dietary restrictions that have proven effective (Austad and Hoffman 2021; Dorling, Martin and Redman 2020; Liang and Wang 2018; Longo and Anderson 2022; López-Otín et al. 2023; Ros and Carrascosa 2020; Shetty et al. 2018).

 Q0.2. Purpose. The purpose of this intervention is to extend the duration of healthy life to delay the onset of age-associated hallmarks.

 Q0.3. Alternatives. As an alternative to CR, drugs are being developed in laboratories that mimic the effects of CR on the body, thus being potential anti-aging drugs. These drugs are part of the second group of interventions to be assessed in this article. The development of such alternatives is important since CR is a demanding practice, requiring rigorous monitoring that can be difficult to comply with. Another alternative that is currently under development is anti-aging gene therapy, which will be assessed in the third group of interventions (Campisi et al. 2019; Coman and Vodnar 2020; Du et al. 2021; Li et al. 2021; Liang and Wang 2018; Longo and Anderson 2022; López-Otín et al. 2023; Mahmoudi, Xu and Brunet 2019; Qian and Liu 2018; Ros and Carrascosa 2020; Tsai et al. 2021).

 Q0.4. Efficacy. There is consistent scientific evidence showing that the rate of aging can be delayed by altering the amount and type of nutrients, as well as eating patterns that regulate them. In humans, clinical trials to evaluate the effects of long-term CR are recent and have been conducted for a limited time. Most notable are the comprehensive assessment of long-term effects of reducing intake of energy (CALERIE) clinical trial (NCT00427193) and the documented experience of members of the CR society known as caloric restriction with optimal nutrition. Data from these studies show that CR improves the metabolic state of the body, delays biological aging, and could therefore increase longevity (Austad and Hoffman 2021; Dorling, Martin and Redman 2020; Longo and Anderson 2022; Ros and Carrascosa 2020). A recent study in humans showed that after 14% CR for 2 years (without following a specific diet), the activity of the thymus significantly improved, resulting in a rejuvenated organ. Changes were also observed in the gene expression of adipose tissue that could help to reduce inflammation and extend the health span (Spadaro et al. 2022). The long duration of these types of trials and the variability of the studies make it difficult to obtain conclusive results in humans (Liu 2022; Ros and Carrascosa 2020).

 Q0.5. Risks. These types of interventions present some risks that must be taken into account. A decrease in bone mineral density was detected in the CALERIE clinical trial (Villareal et al. 2016). In addition, multiple variables, such as genetic background, sex, percentage of CR, time of initiation, and duration of the intervention, as well as the composition of the diet and the metabolic and genetic status of each person may condition the results (Campisi et al. 2019; Longo and Anderson 2022; Ros and Carrascosa 2020), and life shortening has even been found in some strains of mice (Ros and Carrascosa 2020).

 Q0.6. Overcoming inequalities. This is not an intervention that solves a situation of inequality. While it is true that old age is a condition that limits the participation of people in certain activities, to date, it is simply conceived as another stage of life with its specific characteristics. Furthermore, this intervention would not end aging but would only postpone it.

 Q0.7. Social and environmental impact. These types of interventions can have a great impact on society since the delay in population aging brings a series of important social and environmental consequences, such as postponing the retirement age or the increasingly accentuated inversion of the population pyramid, among others (Estes 2001; Lin and Cui 2021; Mahmood and Dhakal 2022; Shrestha 2000). The analysis of these consequences is beyond the scope of this work.

 Q0.8. Legality. There is no specific legislation on CR. Several clinical trials have been authorized in humans to deepen our understanding of this technique. In addition, being a diet, for the present, it is understood that an individual is free to submit to it voluntarily.

 Q0.9. Financial cost. It does not entail an additional financial cost.

 Q0.10. Accessibility. All those who are aware of this option and decide to apply it have access to this technique.

Pharmacological Interventions

Drug therapies to treat aging are still in the early stages of development and require serious critical evaluation in clinical trials to determine their long-term efficacy and the absence of adverse effects on the function of various tissues and organs (Ros and Carrascosa 2020; Shetty et al. 2018).

 Q0.1. Description. In general, these interventions propose undergoing pharmacological treatments to delay aging. The dose and duration of treatment may vary.

 Q0.2. Purpose. The aim of this therapy is to keep the body in healthy and young biological conditions, preventing the onset and perpetuation of the hallmarks of aging.

 Q0.3. Alternatives. Currently, the alternatives to prolong life are CR, discussed above, and gene therapy, which will be described in the next section.

 Q0.4. Efficacy and Q0.5. Risks. The mechanisms of action of the drugs most seriously considered by experts as anti-aging are described below: metformin, rapamycin, resveratrol, senolytics, and senomorphics, although many other drugs are being considered (Kulkarni et al. 2022; Liu 2022).

Rapamycin

Rapamycin is an immunosuppressant prescribed to transplant patients and acts by inhibiting cell growth and as an immune modulator through the inactivation of mammalian target of rapamycin (mTOR), an important kinase involved in the regulation of various cellular processes (Campisi et al. 2019). It is currently being studied as a potential anti-aging drug, as it has been shown to significantly extend lifespan in yeast, flies, and mice (Campisi et al. 2019; DeVito et al. 2022; Ferrara-Romeo et al. 2020; Kulkarni et al. 2022; Li et al. 2021; Liu 2022; Qian and Liu 2018; Ros and Carrascosa 2020). Rapamycin can reproduce a state of nutrient scarcity in the cell, which triggers a compensatory response that is able to extend longevity in mice (López-Otín et al. 2023). It also stimulates autophagy (Mahmoudi, Xu and Brunet 2019; Qian and Liu 2018; Shetty et al. 2018), improves the immune response (Campisi et al. 2019; Ferrara-Romeo et al. 2020), reduces DNA damage accumulation (Kulkarni et al. 2022), helps to improve cognitive function and reduces cancer (Ferrara-Romeo et al. 2020; Li et al. 2021), and improves proteostasis and stem cell function in the epidermis, hematopoietic system, and intestine (López-Otín et al. 2023).

The use of rapamycin as an anti-aging therapy also has certain limitations. First, it has a great immunosuppressive effect that must be taken into account (Qian and Liu 2018). To solve this problem, drugs analogous to rapamycin are being synthesized, in addition to studying the best way to adjust the dose (Ros and Carrascosa 2020). Further, there are still mechanisms of action of rapamycin that need to be clarified since some unwanted effects have been detected. For example, subjecting male mice to long-term rapamycin overdose causes the inhibition of mTORC2 expression, which can result in metabolic dysfunction and decreased lifespan (Li et al. 2021). Rapamycin treatment has also been shown to be harmful in mice with short telomeres and telomerase deficiency (Ferrara-Romeo et al. 2020).

Metformin

Metformin is a drug that has been widely used for decades to treat type 2 diabetes (T2D). However, in recent years, there is considerable evidence to suggest that it could be prescribed as an anti-aging drug. It has been shown to extend the lifespan and healthspan in the nematode Caenorhabditis elegans and in mice (Kulkarni et al. 2022; Lagoumtzi and Chondrogianni 2021; Ros and Carrascosa 2020; Soukas, Hao and Wu 2019). In humans, the use of metformin has been shown to improve health status, extend the lifespan, and decrease mortality (Campisi et al. 2019; DeVito et al. 2022; Li et al. 2021; Mahmoudi, Xu and Brunet 2019; Ros and Carrascosa 2020; Soukas, Hao and Wu 2019).

Metformin has several mechanisms of action: it acts on the mitochondrial respiratory chain, reducing ROS levels (Li et al. 2021; Ros and Carrascosa 2020); inhibits the activity of the complex mTORC1 (Li et al. 2021; Soukas, Hao and Wu 2019); modulates age-related gene expression (Soukas, Hao and Wu 2019); and increases the population of beneficial bacteria in the intestine (intestinal microbiota), contributing to weight loss and the suppression of inflammation in people with T2D (Coman and Vodnar 2020; Du et al. 2021; Soukas, Hao and Wu 2019;). There is also evidence in worms and mice that metformin extends life by inducing a low-energy state that elicits a compensatory response to stress (Kulkarni et al. 2022; Li et al. 2021; Liang and Wang 2018; López-Otín et al. 2023; Qian and Liu 2018; Ros and Carrascosa 2020). More recently, a large-scale clinical trial known as Targeting Aging with Metformin (TAME), which follows the geroscience approach, is expected to launch, but food and drug administration approval for aging as a therapeutic indication is required (American Federation for Aging Research n.d.).

The use of metformin to treat aging has some limitations. In the long term, it can cause vitamin B12 deficiency in diabetic patients (Li et al. 2021; Soukas, Hao and Wu 2019). The most important thing to note is that the mechanisms of action of the drug are still largely unknown (Ros and Carrascosa 2020; Soukas, Hao and Wu 2019). Researchers have identified 745 proteins that are altered after metformin intake (Soukas, Hao and Wu 2019), and it is not known whether its effect is always beneficial or can become harmful if taken preventively against aging (Li et al. 2021; Soukas, Hao and Wu 2019). Due to the heterogeneity and variety of modes of action of metformin, as well as other factors such as the dose, treatment time or the conditions of each patient (comorbidities, age, sex, genetic burden, etc.), an individualized approach may be needed to implement treatments with this drug (Soukas, Hao and Wu 2019).

Resveratrol

Resveratrol is an antimicrobial compound (phytoalexin) present in many plant species, such as grapes and peanuts. As a drug, it mediates the activation of the sirtuin family, proteins that epigenetically regulate gene silencing, contribute to healthy aging, and whose loss of function shortens the lifespan (López-Otín et al. 2023). It could therefore be used to reverse epigenetic DNA alterations through the regulation of histones (Campisi et al. 2019; Li et al. 2021; López-Otín et al. 2023).

Resveratrol has been shown to increase lifespan in mice and nonhuman primates (Campisi et al. 2019; Liu 2022; Qian and Liu 2018). Through different mechanisms, such as promoting proper elimination of ROS (Liu 2022), it can attenuate senescence, reduce inflammation, and improve some cognitive functions (Li et al. 2021; Mahmoudi, Xu and Brunet 2019; Ros and Carrascosa 2020), as well as protect against some age-related diseases (Qian and Liu 2018; Ros and Carrascosa 2020). Some beneficial effects of resveratrol are associated with the maintenance of healthy gut microbiota (Du et al. 2021).

However, conflicting conclusions have been observed in clinical trials with resveratrol in humans, which call into question its effectiveness as an anti-aging drug, having failed to demonstrate a significant improvement in health (Li et al. 2021). Furthermore, its low bioavailability limits its clinical application (Campisi et al. 2019; Li et al. 2021; Liu 2022), as do its low potency and limited target specificity (Campisi et al. 2019).

Senolytics and Senomorphics

Recent studies suggest that the control of cellular senescence significantly improves the healthspan and may prolong life and improve health status (Lagoumtzi and Chondrogianni 2021; Li et al. 2021; Shetty et al. 2018; Tchkonia, Palmer and Kirkland 2021). Senolytics selectively eliminate senescent cells by inducing apoptosis (Lagoumtzi and Chondrogianni 2021; López-Otín et al. 2023; Mahmoudi, Xu and Brunet 2019; Mkrtchyan et al. 2020; Neves and Sousa-Victor 2020; Qian and Liu 2018), while senomorphics affect their function by blocking the senescent-associated secretory phenotype but without killing the senescent cells (Lagoumtzi and Chondrogianni 2021; López-Otín et al. 2023). There are numerous examples of drugs that act as senolytics or senomorphics. Curcumin (Liu 2022), quercetin, and fisetin, among others (Blagosklonny 2021; Lagoumtzi and Chondrogianni 2021; Melo Pereira, Ribeiro and Logarinho 2019), are the most noteworthy. Metformin, rapamycin, and resveratrol, as previously described, also have a senolytic effect (Lagoumtzi and Chondrogianni 2021).

A more comprehensive study of these types of drugs is still required to be able to demonstrate their effectiveness in prolonging the life- and healthspan (Melo Pereira, Ribeiro and Logarinho 2019). Some senolytics are now in clinical trials (López-Otín et al. 2023). It is important to note and carefully investigate possible adverse effects that may occur as a result of chronic administration of senomorphics or permanent elimination of senescent cells (Lagoumtzi and Chondrogianni 2021; Li et al. 2021; McHugh and Gil 2018). Beyond studying their efficacy, the tolerability, safety, and specificity of these drugs should be analyzed in detail to allow their use (Lagoumtzi and Chondrogianni 2021; Li et al. 2021).

 Q0.6. Inequalities and Q0.7. Social and environmental impact. The answers provided for these questions in the previous section also apply to pharmacological interventions. However, looking ahead to the near future, the conditions of inequality that would arise if use of this type of medication were to become widespread would be made worse with respect to people who may not have access. As described, many variables can affect the efficacy of the drug and personalized medicine could be a more realistic and effective option, which would further hinder equal access to treatment. This would inevitably lead to a division in society between those who do have access to treatment, who would enjoy greater benefits, and those who do not.

 Q0.8. Legality. Although some of the drugs are already on the market for treatment of some diseases, no drug has been approved by the competent authorities for specific use as an anti-aging treatment.

 Q0.9. Financial cost. The financial cost associated with these treatments cannot be known today.

 Q0.10. Accessibility. Not on the market.

Anti-aging Gene Therapy

Q0.1. Description. Cell reprogramming is a promising technique that reverts somatic cells to an undifferentiated and pluripotent state through epigenetic changes, giving rise to what are known as induced pluripotent stem cells (Alle et al. 2021; de Lima Camillo and Quinlan 2021). Using four transcription factors – Oct4, Sox2, Klf4, and c-Myc (known as Yamanaka factors) – cell rejuvenation can be achieved by inducing the expression of pluripotency marker genes (Takahashi and Yamanaka 2006). It has been shown that, using the clustered regularly interspaced short palindromic repeats technique, the pluripotency network is activated with only the overexpression of Oct4 or Sox2 (de Lima Camillo and Quinlan 2021). The cellular reprogramming of senescent cells and progenitor cells becomes more important because of its long-term impact (López-Otín et al. 2023). Additionally, gene therapies that specifically target some of the 12 hallmarks of aging have been proposed. Thus, gene therapy strategies are being developed that activate telomerase or that inactivate the histones involved in cell senescence (López-Otín et al. 2023).

 Q0.2. Purpose. The main objective is to reverse the biological hallmarks of aging present in the body to return to a state of young health, thus significantly extending the healthy lifespan.

 Q0.3. Alternatives. The alternatives are the nutritional and pharmacological strategies described above.

 Q0.4. Efficacy. Cell reprogramming has been shown to reduce the negative effects of aging in different tissues by restoring cell functionality through a process of dedifferentiation–redifferentiation (Alle et al. 2021; López-Otín et al. 2023; Mahmoudi, Xu and Brunet 2019). In order to give this technique a therapeutic anti-aging use, partial reprogramming should be implemented, in such a way that the age-related epigenetic changes are reversed without reaching dedifferentiation (Alle et al. 2021; de Lima Camillo and Quinlan 2021; Zhang et al. 2022). This strategy has already been shown to drastically reduce the aged phenotype and age of the DNA, achieving an improvement in longevity and, in general, health (Alle et al. 2021; de Lima Camillo and Quinlan 2021; Mahmoudi, Xu and Brunet 2019; Melo Pereira, Ribeiro and Logarinho 2019; Zhang et al. 2022). Recently, aging has been reversed through partial cell reprogramming techniques in mice safely and effectively in the long term, avoiding the appearance of tumors (Browder et al. 2022). The partial reprogramming technique can be complemented with techniques for introducing juvenile factors, which have also been shown to improve health and extend the lifespan in mice. This other technique involves transplanting organs from young organisms to older individuals, forming “heterochronic age chimeras” (Zhang et al. 2022).

 Q0.5. Risks. Although this therapy is really promising (Mahmoudi, Xu and Brunet 2019; Melo Pereira, Ribeiro and Logarinho 2019), it is not without significant limitations. First, low efficacy has been reported, as well as heterogeneity in results depending on cell age, teratoma formation, and persistence of certain epigenetic marks (Alle et al. 2021; Mahmoudi, Xu and Brunet 2019). Moreover, there are also difficulties in providing this therapy (de Lima Camillo and Quinlan 2021). In conclusion, much of the biological foundations of rejuvenation remains unknown, and the current side effects induced by these interventions (especially reprogramming) currently preclude their clinical application in humans (Zhang et al. 2022).

 Q0.6. Inequalities and Q0.7. Social and environmental impact. Apply the answer provided for these two questions in the section “Pharmacological Interventions” here.

 Q0.8. Legality. Gene therapy in humans is currently not legalized, mainly due to concerns regarding the safety of the technique.

 Q0.9. Financial cost. Sufficient data are not available today to estimate the economic cost associated with this therapy.

 Q0.10. Accessibility. Not on the market.

Analysis of the Interventions According to the Four Principles Proposed by Sgreccia

Principle 1. Principle of Defense of Physical Human Life

Nutritional interventions comply with the first principle of personalist bioethics, since they do not put the life of any human being at risk, either in the development or in the implementation of the technique. As for pharmacological interventions, given that they are currently in the experimental phase, the risks are not considered acceptable due to the great lack of knowledge of the short- and long-term health implications. For this reason, these types of therapy do not currently comply with the first personalist principle because people's lives are put at risk. In the same way, genetic techniques to treat aging are not acceptable from the perspective of personalist bioethics in their current state of development. Although they are very promising, the health risks to those undergoing therapy are unacceptable.

Based on the guidelines, the assessment of the pharmacological and genetic interventions would be concluded here, classifying them as unacceptable. However, in order to be able to apply the guidelines preemptively and to discern whether they could be considered as ethically acceptable if they were safe, the following questions will be answered under the assumption that their safety has already been proven.

An important aspect to assess in genetic interventions is the use of embryos (Q1.2). Techniques based on iPSC cells would avoid their use to obtain pluripotent cells with regenerative capacity. However, the use of embryonic cells is still considered a potential treatment for the development of rejuvenation techniques. Moreover, as research in this field advances, there is the possibility of testing therapies in human embryos to evaluate their efficacy or even replacing induced pluripotent stem cells with cells derived from embryos because they work better in terms of safety and efficacy. In this case, they would not be considered licit practices from the personalist perspective because they undermine the dignity of the human being in an embryonic state, being treated as manipulable and disposable biological material.

Principle 2. Principle of Totality or Therapeutic Principle

With respect to nutritional interventions, it is concluded that they are not entirely therapeutic since they do not seek to cure a specific disease. Nevertheless, they are intended to restore the proper functioning of cells and tissues, which may present some deterioration due to the passage of time, contributing to the onset and/or progression of various diseases. Although the aging phenotype cannot yet be observed in the person, this therapy could reverse nonvisible cell damage to prevent or delay the onset of noticeable complications. A point in its favor is that it does not alter the morphology or the normal physiology of human nature, and the risk–benefit balance would be favorable in principle.

With regard to pharmacological interventions, in the hypothetical case where it was rigorously proven that they were safe techniques, they would not undermine the integrity of the individual, thus respecting the second personalist principle. Considering genetic interventions, it should be taken into account that genome modification is considered an invasive intervention that affects physical integrity, so it would not be considered licit to perform it preventively; it should be carried out only for a genuinely therapeutic purpose, acting on the cause of an existing impairment to alleviate it, provided it has met the condition that there was no other less invasive alternative. Moreover, it should be added that genetic interventions are also considered those that seek to silence or activate genes that are naturally found in our genome. If this genetic modulation is performed reversibly, it would not alter the genetic integrity of the individual; if it were irreversible, it would indeed alter it and should be performed only for therapeutic purposes and when there are no comparable alternatives.

Principle 3. Principle of Freedom and Responsibility

Assuming, as previously described, that it is a completely free decision and that the health implications are known, nutritional interventions are considered to respect and foster the freedom and responsibility of the person since they allow realization of the person according to their natural purposes, without endangering or damaging the life and/or personal identity (intimate experiences, memories, etc.) of themselves or others. Using this technique, the person can achieve their legitimate goal, leaving aside the use of artificial techniques or substances that could be unnecessary and resorting to safer ways. With regard to pharmacological interventions, they would also adhere to this principle. It would be essential that all relevant information be described in the package insert. Finally, with regard to gene therapy interventions, it is critical to consider how this therapy is used. It will only be licit when it is applied to tissues of the adult body that are not involved in reproduction and provided that the use of embryos is avoided in the development of therapies.

It should also be noted that, compared to the other alternatives (drugs and gene therapy), nutritional interventions are the least invasive and less artificial option. Thus, if the efficacy and benefits obtained are comparable, it would be the preferable option since it would likely alter the organic integrity of the individual as little as possible. However, once objective results are available, the risks/benefits of each option will have to be assessed, as well as variables such as efficacy, treatment duration, form of administration, frequency required, and so forth.

Principle 4. Principle of Sociability and Subsidiarity

Nutritional interventions would also respect this principle since they involve a diet that people can opt for on a voluntary basis. Assuming the possibility of having access to suitable foods, the only impediment to accessing it could be lack of knowledge, lack of will, or some physiological or health condition preventing it. As for pharmacological interventions, even if these drugs were affordable for the population of average socioeconomic level, it would entail a cost for the individual that could become a fixed and prolonged expense over time. The objective pursued, to restore an impaired state of health (even at a cellular level not yet perceptible), is acceptable since it is not a question of trying to increase the chances of success in a competitive environment, improve only aesthetically without therapeutic reasons, and so on. Nonetheless, it cannot currently be ruled out that, in future, these interventions will provide a competitive advantage.

Finally, based on the therapies currently being developed, it can be assumed that genetic interventions would not be widely affordable for people due to their high cost. This factor, together with the fact that the other two alternatives are expected to be more affordable, leads us to consider that this type of intervention would not comply with the fourth principle. However, they are still at too early a stage of development to know what the estimated cost would be, which is based on many factors (public or private funding, technology used, treatment time and dose required, etc.).

Table 2 compares the results obtained after subjecting each of the intervention groups to the guidelines for the ethical assessment of interventions on the human body.

Table 2.

Comparison of the Answers to the Guidelines for the Ethical Assessment of Interventions on the Human Body Applied to the Three Types of Anti-aging Interventions Examined: (1) Nutritional Interventions; (2) Pharmacological Interventions; and (3) Genetic Interventions.

	1	2	3
First principle. Questions to evaluate whether the technique violates the principle of defense of physical human life.
Q1.1. Will the intervention endanger your life or that of another human being?	No	Yes	Yes
Q1.2. Has it originated from illicit practices with respect to the value of human life?	No	No	No
Q1.3. Are the risks to your physical, mental, or spiritual health greater than the benefits? (Assess whether the technique has been correlated with the onset of any disease or disorder, or if it is an experimental intervention).	No	Yes	Yes
Q1.4. Is it an intervention to save life or significantly improve a seriously impaired state of health, even if it carries risks?	-	No	No
Q1.5. Is there a consensus from a medical professional perspective to conclude that it is the solution with the best prognosis with respect to the preservation of life and health, among all possible alternatives, including that of not performing any intervention?	-	No	No
Second principle. Questions to assess whether the technique violates the principle of totality or therapeutic principle.
Q2.1. Is it part of the treatment of a properly diagnosed disease or pathology?	No	No	No
Q2.2. Is it intended to reduce unusual discomfort or pain, or to restore an impaired body part in yourself or another person?	Yes	Yes	Yes
Q2.3. Do you expect to be able to perform the same natural organic functions of a healthy individual after the intervention?	Yes	Yes	Yes
Q2.4. Does the technique involve amputation, disfigurement, or replacement of a healthy part of the body (limb, organ, tissue, genome, etc.)?	No	No	Yes
Q2.5. Is the normal morphology and/or physiology of human nature altered?	No	No	No
Third principle. Questions to evaluate whether the technique violates the principle of freedom and responsibility.
Q3.1. Is it a germline genetic modification technique that involves in vitro generation of embryos?	No	No	No
Q3.2. If you are pregnant, could the effects of the technique be harmful to your baby and could you postpone it? (Consider the medical criteria to understand the risks to the baby of both performing the technique and not performing it),	No	No	No
Q3.3. Is the enhancement aimed at the promotion of the person's own ends, to their growth in virtues and to love as a guiding element of their actions?	Yes	Yes	Yes
Q3.4. Have you opted for the technique that you are now assessing after learning about and evaluating all possible alternatives according to their characteristics (methodology, persistence, nature, etc.), their risks and their expected results?	Yes	Yes	Yes
Q3.5. Is the decision you are assessing born of your free will and a personal reflection irrespective of the social pressure that family, friends, trends, etc. may exert?	Yes	Yes	Yes
Q3.6. Will your will and your perception of reality remain unchanged after the practice? (Consider the possibility of generating serious changes in habitual behavior or addictions or obsessions by wanting to repeat the practice).	Yes	Yes	Yes
Q3.7. Have you been duly informed of all potential short-, medium-, and long-term side effects; rights; and obligations, and do you assume them responsibly? Do you know your country's legislation in this regard?	Yes	Yes	Yes
Q3.8. Will your personal identity be protected (intimate experiences, memories, etc)?	Yes	Yes	Yes
Fourth principle. Questions to assess whether the technique violates the principle of sociability and subsidiarity.
Q4.1. Is it a technique inaccessible to the population of average socioeconomic status because high purchasing power is needed and there is no public funding option?	No	Yes/No	Yes
Q4.2. Will it provide a clear competitive advantage to achieve goals (jobs, awards, sports medals, etc.) much more easily than people who have not undergone the technique?	No	Yes/No	Yes/No
Q4.3. Is the main purpose of the technique therapeutic, even if it has as an unintended effect by itself having some enhanced natural human capacity with respect to the average of the surrounding population? (Consider whether the goal sought is to restore an impaired state of health).	-	Yes	Yes
Q4.4. Do you consider that the cost of the technique is optimal with respect to the benefits it provides and the possible alternatives that are more affordable or that involve less distinction with respect to the capabilities of the average society?	-	Yes	No

Unacceptable

Acceptable

Conclusions

From a personalist perspective, the body is not a mere instrument of the self but an essential expression of the person. Any biomedical intervention, including anti-aging therapies, must therefore respect the dignity, integrity, and finality of the human body. Based on the analysis carried out from the four principles of personalist bioethics proposed by Sgreccia (2012), we conclude that interventions that consist of healthy control of the diet based on CR, combining it with an active lifestyle that includes physical exercise, seems to be the option that presents fewer bioethical drawbacks today. This strategy promotes noninvasive and natural care of physical and mental health, if followed in a controlled and nonobsessive manner, with the healthy intention of maintaining an optimal state of health that allows one to enjoy the gift of life while accepting and embracing one's own weakness and vulnerability, as well as that of others.

In view of the above considerations, gene therapies are ruled out based on the current data, mainly for safety reasons. Drug-based treatments are not currently considered licit at this time either, although it should not be forgotten that many of the drugs that are considered potential anti-aging therapies are already marketed for other purposes (such as metformin prescribed for T2D, for example); therefore, it can be assumed that their use in humans could become licit if a dosing regimen that guarantees safety and efficacy for patients can be defined, taking into account the biological conditions of each person. This requires relevant clinical trials that analyze the long-term effects of the drugs.

Therefore, nutritional interventions, by supporting natural physiological processes, align more closely with personalism. In contrast, irreversible genetic modifications or pharmacological manipulations are more dangerous, and they risk reducing the body to a manipulable object, especially when performed without clear therapeutic justification.

From a broader philosophical and long-term perspective, in personalist thought, the concept of person is threefold (body, mind, and spirit), understanding these three dimensions as part of an indissoluble unit. Therefore, the proposed therapy must also contemplate the psychological and spiritual consequences that may result from following it. Accordingly, it must be borne in mind that the fact of fighting against the passage of time, wanting to avoid, ultimately, death, can affect the mental and spiritual health of the person. Undergoing these anti-aging therapies can generate an obsession with controlling one's lifespan and physical life, wanting to take ownership of it without accepting the reality that it is limited and finite. The drive toward radical life extension or rejuvenation may stem from a technocratic mindset that seeks mastery over natural limits. Personalist bioethics calls instead for discernment: not all that is technically possible is ethically desirable. Subordinating human identity to a paradigm of indefinite optimization potentially undermines existential acceptance of finitude, vulnerability, and the meaning of aging within the human life cycle. Today, aging and death are inevitable. However, understanding life as a gift, accepting that it is limited, gives it a new and deeper meaning that can inspire us to live more fully.

Hence, it should be reaffirmed that, although it is good to try to stay healthy, promote health, and cure diseases since it implies a respect for physical life, we must also know how to embrace the weakness of human nature that is accentuated in a special way in old age. In this respect, it is important to consider the difference between what we might call aging and old age. When it comes to anti-aging therapies, we run the risk of consolidating a mentality of rejection toward frailty, vulnerability, old age, and death, these being characteristics of the human condition that must be accepted in order to foster full respect for the dignity of people, not conditioned by their state of health. The consequences of such an approach could lead to discriminatory attitudes that would be exacerbated if the final cost of treatment meant that it was not accessible to the entire population. However, from a personalist bioethics, it is considered acceptable and advisable to act against physical decline, whether associated with the years or another cause, while distinguishing this concept (aging) from that of old age, which does not have to be associated with a state of ill health but rather with a life experience that is valuable for society.

Additionally, genetic and pharmacological interventions, particularly if costly or limited to a privileged few, could reinforce socioeconomic disparities. Thus, even if proven safe, their liceity would depend not only on individual autonomy but also on considerations of justice, solidarity, and equitable access—key elements of the principle of sociability and subsidiarity.

Beyond being able to determine when a treatment is acceptable or not, a deeper approach to issues such as aging and death leads us to wonder about the value with which we treat life. The principle of defense of human life is not only about not putting it at risk but also about respect for each person in their life and in their inherent dignity, which leads us to seek the good for them: the realization of the fullness of their being.

Biographical Notes

Ana Rodríguez-Díaz, MS, is a biomedical engineer from the Polytechnic University of Valencia and holds a master's degree in bioethics from the Catholic University of Valencia. Her areas of interest in the field of bioethics include ethics of anti-aging therapies and transhumanism and practical application of personalism to bioethical analysis.

Esperanza Marín-Conde, MS, is a bioethics professor in the medicine degree at the CEU Cardenal Herrera University. She holds a degree in biomedical engineering from Carlos III University of Madrid and a master's degree in bioethics from the Catholic University of Valencia. Currently, she is pursuing her doctoral studies at the University of Valencia in her areas of interest: the relationship between ethics and technology, and bioethics applied to technological developments, especially those that directly affect human nature.

Lucía Gómez-Tatay, PhD, is professor of biology (degree in medicine, degree in dentistry) and bioethics (degree in philosophy, degree in biotechnology, master's degree in bioethics) and member of the Observatory of Bioethics at the Catholic University of Valencia “San Vicente Mártir.” Her research focuses on the ethics of biotechnology developments, particularly synthetic biology, gene editing, or human–animal chimera production. Her other areas of interest include ethics of mitochondrial replacement and practical application of personalism to bioethical analysis.