Advancing Geroscience Research – A Scoping Review of Regulatory Environments for Gerotherapeutics

Highlights

• •Aging lacks disease status, but new classifications are opening regulatory dialogue.
• •Regulatory frameworks are limited, yet trial innovations are moving the field forward.
• •Validated biomarkers are needed, and global efforts toward standardization are growing.
• •Public and policy support is low, but reframing geroscience can build engagement.

Abstract

Background

Globally, older adults are living longer but often in poorer health with multiple chronic conditions straining healthcare systems. Gerotherapeutics, which target the biological mechanisms of aging, could reduce this burden by extending healthspan. However, before therapies can be adopted, they must undergo rigorous study and regulatory approval; existing regulatory frameworks and the barriers to their development are unknown.

Objective

We conducted a scoping review of geroscience regulatory frameworks and identified barriers to their development.

Methods

A comprehensive government, academic, and grey literature search in the United States, Europe, Canada, and other regions including Medline and EMBASE (via OVID), Google Scholar, CINAHL, and CADTH Grey Matters was conducted. For inclusion of only recent literature, searches were limited to English-language publications from 2014 to 2024.

Results

In 3,780 publications screened for inclusion, no regulatory frameworks for gerotherapeutics were found. In the 34 included publications, 4 major barriers were identified: 1) lack of recognition of the biological processes of aging as targets for medical intervention; 2) absence of clear regulatory pathways to evaluate aging-focused therapies; 3) economic uncertainties, including high development costs and limited incentives due to unclear regulatory environments; and 4) insufficient public and policy engagement.

Conclusion

We did not identify any geroscience specific regulatory frameworks but identified barriers to their development. For biological aging to advance as a therapeutic target, stakeholders must develop comprehensive regulatory guidelines, incentivize research and conduct public education. Global collaboration is crucial to harmonize regulatory efforts and ensure equitable adoption of therapies, ultimately enhancing healthspan worldwide.

1. Introduction

The world’s population is aging, with the proportion of older adults rising in nearly every country. By 2030, those aged 60 and over will make up one-sixth of the global population, increasing to one-fifth by 2050 [1]. These demographic shifts affect nations unequally with some nations having more older adults than others and many countries report over 20% of their populations being older than 65 years old [2]. The fastest growing age cohorts are those in the extremes of extremes of age [2]. However, while life expectancy is longer, many older adults spend their later years in poor health with age-related comorbidities, disabilities, functional decline, frailty, and reduced quality of life (QoL) [3,4]. This challenges healthcare systems around the world which are primarily designed around acute care and are ill-equipped to address the growing burden of chronic conditions associated with aging.

To address the negative effects of increased longevity, there has been growing attention on healthy aging and maintenance of intrinsic capacity. Health aging is defined by the World Health Organization (WHO) as “the process of developing and maintaining the functional ability that enables well-being in older age” [5], while intrinsic capacity is defined as the sum of an individual’s physical and mental capacities [6]. While lifestyle interventions targeting physical activity, nutrition and social connectivity are widely recognized as first-line approaches for mitigating age-related decline [7], adherence to these interventions vary, limiting their long-term effectiveness at the population level [8]. Biological aging trajectories and responses to such interventions may also vary across sociodemographic groups, including by sex, socioeconomic status, and race or ethnicity [9]. Given these challenges, innovative strategies to reduce the burden of chronic disease and to extend healthspan, or the time spent in good health, are required. Geroscience, the study of the biological mechanisms of aging and how they contribute to aging related disease, offers promise in this regard [[10], [11], [12]].

Over the past decades, growing insight into the mechanism of aging including the biological processes that underlie multiple chronic conditions has facilitated the development of pharmacological interventions aimed at reducing the burdens of aging [13,14]. These interventions called geroprotectors or gerotherapeutics can be classified according to the mechanism or hallmark of aging that they target [15]. Examples include those that target cell senescence (senolytics), mitochondrial dysfunction (nicotinamide adenine dinucleotide (NAD⁺) boosters and altered nutrient sensing (mTOR inhibitors such as rapamycin) [16,17]. They are increasingly being investigated in humans. As a measure of momentum in the field, as of 2025, ClinicalTrials.Gov lists dozens of studies evaluating therapeutics that specifically target biological aging. This is likely to expand as knowledge of the biology of aging and interest in the field expands.

The advancement of geroscience has the potential to reshape healthcare by shifting the focus from reactively treating age-related diseases to proactively preserving health and functional ability. This shift could reduce the societal and financial costs associated with aging populations [18]. However, before gerotherapeutics can be adopted widely, extensive study of their effectiveness and safety is necessary. Regulatory approval from global agencies such as the United States Food and Drug Administration (FDA), Health Canada, and the European Medicines Agency (EMA) would be required to ensure their safe integration into healthcare systems. To do so, these agencies would need to expand their approval process which is currently disease-based.

While aging itself is not a disease, it is the largest risk factor for many chronic diseases and conditions, including frailty and diminished intrinsic capacity. Notably, the International Classification of Diseases (ICD-11) now includes “aging-associated decline in intrinsic capacity” (MG2A) as a classification, replacing the previous term “old age” [19]. This shift provides a potential regulatory foundation for future gerotherapeutic drug approvals, as it establishes a recognized target for interventions aimed at mitigating age-related declines. Similarly, sarcopenia, a condition characterized by the progressive loss of skeletal muscle mass and function, has been assigned an ICD-10-CM code (M62.84) although consensus on measurement remains elusive [20]. The distinction between disease and the aging process matters for regulators, as current therapeutic approvals are tied to specific conditions (e.g., sarcopenia), whereas therapies designed to target aging biology would fall outside existing disease-based frameworks. If aging is accepted as a therapeutic target, regulatory agencies may need to revise approval pathways, expand eligible endpoints, and support trial designs that reflect the complexity of aging biology rather than traditional single-disease models.

To investigate existing regulatory frameworks and policies that guide geroscience research we conducted a scoping review. Specifically, we sought to identify regulatory gaps and explore the challenges for the development of robust frameworks for geroscience. Herein, we report the findings and propose actionable strategies to advance the discovery and approval of gerotherapeutics.

2. Materials and methods

2.1. Eligibility criteria

A scoping review was conducted to identify regulatory frameworks and policies guiding gerotherapeutics research globally, with a focus on the gaps in existing frameworks and potential challenges that may hinder future development. The review drew from both academic and grey literature, with all study designs eligible, including qualitative and quantitative methods, as well as government reports, policy briefs, or industry publications. The methodological approach was informed by Arksey and O’Malley’s framework for conducting scoping reviews, providing a structured process for examining regulatory environments across multiple countries [21].

2.2. Information sources and search strategy

Two authors conducted searches across Medline and EMBASE (via OVID), Google Scholar, and CINAHL to identify relevant academic literature (see Appendix Supplementary Table 1). Keywords related to geroscience and longevity research including terms such as geroscience, biogerontology, gerotherapeutic, geroprotector, longevity, healthspan, lifespan, anti-aging, pharmacology and drug. Further, terms targeting regulatory contexts, such as public policy, regulatory agency, and regulatory framework, were also searched. Reference lists of included articles were manually searched to identify additional literature that may not have been captured by the search strategy.

Table 1.

Summary of publications discussing challenges for the development of regulatory frameworks for the field of geroscience.

First author and year	Countries	Academic or Grey	Source Type	Challenge/s
Bannister et al. 2014 [42]	UK	Academic	Observational Study	Economic and Industry
Barzilai et al. 2016 [27]	US	Academic	Review Article	Lack of Clear Regulatory Pathways; Economic and Industry
Boekstein et al. 2023 [22]	US	Academic	Correspondence Paper	Aging as a Target
Brouwers et al. 2024 [34]	Netherlands	Academic	Survey Study	Lack of Clear Regulatory Pathways
Burd et al. 2016 [28]	US/EU	Academic	Review Article	Lack of Clear Regulatory Pathways; Economic and Industry
Crane et al. 2022 [36]	UK	Academic	Review Article	Lack of Clear Regulatory Pathways; Economic and Industry
Cummings et al. 2023 [50]	Global	Academic	Review Article	Public and Policy Engagement
DeVito et al. 2022 [43]	Global	Academic	Symposium Report	Economic and Industry
Farrelly, 2024 [52]	US	Academic	Opinion Paper	Public and Policy Engagement
Fight Aging! 2023 [23]	Global	Grey	Opinion/Analysis	Aging as a Target
Fight Aging! 2024 [39]	US	Grey	Opinion/Analysis	Lack of Clear Regulatory Pathways
Fight Aging! 2024 [37]	US	Grey	Opinion/Analysis	Lack of Clear Regulatory Pathways
House of Lords Science and Technology Committee, 2021 [35]	UK	Grey	Committee Report	Lack of Clear Regulatory Pathways; Economic and Industry
Huffman et al. 2016 [46]	Global	Academic	Review Article	Economic and Industry
Justice et al. 2016 [29]	Global	Academic	Review Article	Lack of Clear Regulatory Pathways; Economic and Industry
Kaeberlein, 2017 [10]	US	Academic	Review Article	Lack of Clear Regulatory Pathways; Economic and Industry
Kalafut et al. 2022 [38]	US	Academic	Review Article	Lack of Clear Regulatory Pathways
Kulkarni et al. 2022 [40]	US	Academic	Review Article	Lack of Clear Regulatory Pathways; Economic and Industry
Le Couteur et al. 2022 [47]	Global	Academic	Review Article	Economic and Industry
Leng et al. 2019 [53]	Global	Academic	Review Article	Economic and Industry
Leone et al. 2024 [44]	US	Academic	Review Article	Economic and Industry
Longo et al. 2015 [30]	General	Academic	Review Article	Lack of Clear Regulatory Pathways; Economic and Industry
Marín Penella, 2024 [24]	Europe	Grey	Opinion Paper/Policy Argument	Aging as a Target
Morsli et al. 2021 [41]	UK/EU	Academic	Review Article	Lack of Clear Regulatory Pathways; Economic and Industry
Newman et al. 2016 [31]	Global	Academic	Review Article	Lack of Clear Regulatory Pathways
Nuffield Council on Bioethics, 2023 [48]	UK	Grey	Policy Report	Public and Policy Engagement
Rolland et al. 2023 [16]	US, EU	Academic	Review Article	Aging as a Target; Lack of Clear Regulatory Pathways; Economic and Industry
Sierra et al. 2021 [45]	US	Academic	Review Article	Economic and Industry
Standal, 2024 [25]	Global	Academic	Literature Review	Aging as a Target; Lack of Clear Regulatory Pathways; Public and Policy Engagement
Syed et al. 2022 [26]	UK	Academic	Mixed-Methods Study	Economic and Industry
The Royal Society, 2024 [49]	UK	Grey	Policy Report	Public and Policy Engagement
Tournas et al. 2019 [32]	US	Academic	Review Article	Lack of Clear Regulatory Pathways
United States Congress, House, Subcommittee on Investigations and Oversight, 2022 [51]	US	Grey	Congressional Report	Public and Policy Engagement
Vaiserman et al. 2017 [33]	US	Academic	Review Article	Lack of Clear Regulatory Pathways; Public and Policy Engagement

Note: EU = European Union; General = No country indicated in publication; Global = Indicated data from multiple countries; UK = United Kingdom; US = United States.

Grey literature searches, using the same keywords, were conducted through Google and CADTH Grey Matters to locate health-related publications. We also examined websites of agencies with potential to support geroscience initiatives through their existing drug evaluation and approval processes. This included Health Canada, the FDA, the EMA, the United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA), India’s Central Drugs Standard Control Organization (CDSCO), and Australia’s Therapeutic Goods Administration (TGA).

2.2.1. Inclusion and exclusion criteria for the selection of studies

The search was limited to English-language publications from 2014 to 2024, ensuring the inclusion of literature relevant to recent developments in the field of geroscience. Studies focusing on human subjects were prioritized and if they focussed only on animal literature, they were excluded. While grey literature, predominantly consisting of opinion and policy analysis pieces, was considered for inclusion, academic articles that were editorials or opinion-based were excluded.

2.3. Data extraction and analysis

Two authors independently performed the data extraction. The initial screening involved reviewing titles and abstracts to assess relevance, followed by full-text screening of potentially eligible publications. Extracted data included key insights regarding the state of the regulatory environment, as well as challenges and strategies for advancing geroscience research.

3. Results

3.1. Study characteristics

The search on the combined databases yielded 3,778 studies. No publications described regulatory frameworks or policies for the field of geroscience or gerotherapeutics, but 34 publications focused on describing challenges for the development of these frameworks (Fig. 1). The majority of the publications (n = 26; 76%) included were academic articles and were from the United States (n = 14; 41%; Table 1).

Fig. 1.

Flow chart for study inclusion.

3.2. Challenges for the development of regulatory frameworks for the field of geroscience

The development of regulatory frameworks for gerotherapeutics faces significant challenges, which can be grouped into four main areas: 1) defining aging as a target for medical intervention (n = 6); 2) the lack of clear regulatory pathways (n = 16); 3) economic and industry-related obstacles (n = 15); and 4) public and policy engagement (n = 4; Table 1).

3.2.1. Defining aging as a target for medical intervention

A significant challenge in geroscience is the lack of formal recognition of aging as a treatable condition and concerns that an indication for aging per se would pathologize older adults and exacerbate widespread ageism. Regulatory bodies such as the FDA, the EMA and Health Canada do not classify aging as a disease, which complicates the approval process for therapies targeting aging although the targeting the underlying mechanisms of aging could still be beneficial in preventing age-related diseases [[22], [23], [24]]. This absence of classification limits the development of standardized clinical trial endpoints and regulatory pathways [16,25,26]. For example, only one study—the Targeting Aging with Metformin (TAME) trial—has been approved by the FDA to investigate an intervention targeting multiple age-related diseases rather than a single condition [27]. While the TAME trial does not classify aging as a treatable disease, it provides a precedent for evaluating therapies that address the biological mechanisms of aging, potentially shaping future regulatory frameworks.

3.2.2. Lack of clear regulatory pathways

The absence of standardized regulatory frameworks poses an additional barrier to licensing aging-related interventions. Current regulatory systems are structured for disease-specific therapies and lack mechanisms to evaluate treatments targeting mechanism of aging as a systemic biological process [[27], [28], [29], [30], [31], [32], [33]]. For example, the FDA does not offer clear guidelines for therapies aimed at aging itself, creating uncertainty in clinical trial design and approval [31,34,35]. Further, regulatory inconsistencies and lack of a harmonized approach across countries is a key barrier and contributes to increased development costs and complicates global approval processes [16,27,[36], [37], [38]]. Emerging programs such as the United States’ Advanced Research Projects Agency for Health (ARPA-H) Proactive Solutions for Prolonging Resilience (PROSPR) initiative aim to address these gaps by developing novel clinical trial models and biomarker frameworks that could support regulatory innovation, particularly for interventions targeting resilience and healthspan [39].

Repurposed drugs, such as metformin, face additional regulatory challenges to receive an aging related indication despite their potential for lower development costs [31,40]. While already approved for other indications, these drugs must still demonstrate efficacy in aging-related outcomes [41]. Unlike novel compounds, repurposed drugs do not typically qualify for new regulatory exclusivity, making them less attractive for private investment [29]. As a result, securing funding for large-scale trials often requires alternative strategies, including public funding mechanisms or intellectual property protections for reformulated versions of older drugs [27].

3.2.3. Economic and industry challenges

Economic barriers in geroscience research and development of gerotherapeutics are considerable. High development costs, extended clinical trial timelines, and uncertainty regarding regulatory approval and market pathways discourage investment in aging-related therapies [28,29,[41], [42], [43], [44], [45]]. The commercial viability of repurposed drugs in geroscience research is limited by challenges such as difficulty in securing sufficient investment and demonstrating clear economic returns [16,36,40,46,47]. Innovative trial designs necessary for gerotherapeutics have been reported to increase financial strain on developers [27,29]. Additionally, disparities in funding allocation have been noted as a contributing factor to limited progress in the field [35].

3.2.4. Public and policy engagement

Limited public engagement and policy support have been identified as barriers to advancing geroscience. Ethical and societal concerns surrounding lifespan extension present challenges for prioritizing aging-related interventions [48,49]. Public skepticism regarding the feasibility and desirability of targeting aging has also been cited as a challenge to gaining policy support [50]. A key aspect of this skepticism relates to concerns over who would benefit from these interventions and whether they would primarily serve those with greater financial and healthcare access [48]. Equity concerns, including the potential for longevity interventions to disproportionately favor wealthier individuals, have been raised in policy discussions [51]. The framing of geroscience as either extending lifespan or improving healthspan further shapes public perception [50,52]. While interventions to prevent diseases such as cancer and heart disease are widely supported, positioning these treatments within the framework of slowing aging itself elicits both enthusiasm and skepticism [25,33]. This polarization may contribute to the limited governmental engagement in the field of geroscience [51], despite evidence that public understanding plays a critical role in shaping policy for aging research [33,52]. Communication challenges further influence public perception and policy development [16,25]. Additionally, gaps in public engagement have been identified as a barrier to aligning societal priorities and geroscience advancements [23].

4. Discussion

In this scoping review, we did not find any regulatory frameworks by government agencies, such as the FDA or the EMA, for gerotherapeutics. While there has been progress, including discussions on refining clinical trial designs in the United States and Europe, we identify the challenges faced by the field that need to be addressed going forward. These include the lack of recognition of aging as a therapeutic target, unclear regulatory pathways, economic constraints, and insufficient public and policy engagement. Table 2 summarizes these barriers and highlights potential solutions drawn from the literature to guide future efforts in gerotherapeutic development. Collectively, these barriers have hindered and unless addressed, will continue to hinder the development and implementation of interventions targeting the biological mechanisms of aging.

Table 2.

Key challenges and solutions to advance gerotherapeutic development.

Barrier 1: Aging as a Therapeutic Target	Barrier 2: Lack of Clear Regulatory Pathways	Barrier 3: Economic and Industry Related	Barrier 4: Public and Policy Engagement
Solution 1a: Formally recognize mechanisms of aging as legitimate targets for intervention.	Solution 2a: Develop regulatory frameworks that accommodate interventions targeting aging biology rather than single diseases.	Solution 3a: Clarify that not all aging trials require long-term follow-up to demonstrate meaningful benefit.	Solution 4a: Launch public education campaigns that frame geroscience as improving healthspan, not just lifespan.
Solution 1b: Integrate aging into conceptual models of chronic disease to catalyze intervention before disease onset.	Solution 2b: Incorporate adaptive approval pathways and innovative trial designs suitable for gerotherapeutics.	Solution 3b: Provide targeted incentives such as public–private partnerships, dedicated grant programs, or tax credits to reduce investment risk.	Solution 4b: Address ethical concerns (e.g., fairness, access, resource allocation) in public-facing communications.
Solution 1c: Support development of clinical endpoints that reflect the multifactorial and progressive nature of aging.	Solution 2c: Support initiatives to test and refine real-world endpoints and biomarkers for regulatory use.	Solution 3c: De-risk early-stage development by supporting platform trials or shared infrastructure for aging studies.	Solution 4c: Position gerotherapeutics as a public health strategy for reducing the burden of chronic disease and disability.
Solution 1d: Encourage regulatory acceptance of aging-related composite outcomes.	Solution 2d: Provide regulatory guidance on trial design, endpoint selection, and aging-related indications to reduce uncertainty.	Solution 3d: Foster clearer pathways to approval to encourage commercial interest and reduce perceived regulatory risk.	Solution 4d: Develop accessible messaging to engage both the general public and policymakers.
	Solution 2e: Promote inclusion of aging in regulatory science agendas at agencies such as FDA and EMA.		Solution 4e: Strengthen advocacy coalitions to align geroscience with broader aging and health equity agendas.

Regulatory barriers remain a foundational obstacle. Regulatory pathways are complex, multistage and encompass everything from adequate pre-clinical study, sequential phased trial designs utilizing appropriate endpoints including validated biomarkers, regulatory classification and market approval [54]. All of these would need to be tailored to an aging intervention. The traditional focus by regulatory agencies on well-defined diseases and disease-specific endpoints has resulted in the absence of regulatory frameworks for this indication [27,28]. A starting point for regulatory agencies and therapeutics for aging may be the inclusion of age-related decline in intrinsic capacity (MG2A) in the ICD-11 as a replacement of “old age” [55]. Preservation of intrinsic capacity can be measure of health span and it is quantifiable although the measurement instruments need refinement [56]. However, if the goal of gerotherapeutics is to prevent chronic disease, then this indication would not be adequate since the indication would only be met if the occurrence of chronic disease had functional impact, which in many instances is impacted by the social and health care circumstances of the individual. Further, the development of gerotherapeutics regulatory frameworks will require integration of aging within the conceptual causal pathways of chronic disease. Recognizing aging as a legitimate therapeutic target would provide researchers and stakeholders with clarity, enabling the design of interventions that reflect the multifactorial and individual-specific nature of aging [24].

As regulatory frameworks develop and evolve, incorporating adaptive approval pathways and trial designs that accommodate the complexity of aging will be key to accelerating progress. Innovative regulatory pathways are in place in agencies around the world in response to unmet needs or perceived urgency such as the EMA’s Adaptive Pathway or the FDA Accelerated Approval Program. While these would be difficult to adapt to an aging indication since they are based on regulatory processes already in place, they demonstrate the willingness of agencies to adapt to needs or new evidence. This could be provided by the PROSPR program in the United States that aims for the development of novel clinical trial designs, real-world resilience metrics, and biomarker strategies as a strategy for accelerating gerotherapeutic development [39]. Although its success remains to be seen, PROSPR offers a model for how regulatory and scientific innovation could converge to support healthspan-focused therapies. Without regulatory frameworks, researchers and industry stakeholders will likely face continued uncertainty, limiting progress in translating geroscience advances into clinical practice.

Methodological considerations further complicate trial development. Although measuring aging is not inherently difficult—given the availability of deficit accumulation indices and multimorbidity assessments—these models do not yet fully align with conventional approval processes structured around single-disease interventions [40,41]. The challenge is defining appropriate validation methods for gerotherapeutics, particularly the selection of clinical endpoints and surrogate markers [16]. The TAME trial incorporated multiple chronic conditions, which are routinely measured and familiar into a composite endpoint, and may represent a feasible pathway for evaluating gerotherapeutics [27]. While TAME provides an important precedent that could shape future regulatory pathways, the utilization of composite endpoints requires careful consideration. In particular, the interpretation of a composite endpoint outcome for aging research requires considerations such as, are all the elements patient centered and important to patients and their caregivers? Are all the outcomes of equal importance? In response to an intervention, are they all expected to respond in the same direction [57]? A priori, planning for the analysis of composite outcomes and their components will be important and this should be published before the conclusion of a trial. Involvement of patients and families in the selection of composite outcomes measures will be important for their formulation. Further, to ensure the validity and interpretability of composite endpoints for geroscience trials, validation in databases outside the trial, such as those of longitudinal studies of aging, with subsequent publication, would allow scientific debate and re-use of the endpoint across trials.

The validation and standardization of biomarkers also remain key challenges. Reliable biomarkers are another essential component for advancing gerotherapeutics. Biomarkers provide insights into the biological processes of aging and their relationships with health outcomes, serving both to evaluate interventions and identify individuals who may benefit from specific therapies [58]. Biomarkers can be categorized into those reflecting the pathophysiology targeted by treatments (e.g., senescent cell burden for senolytics), those measuring biological age (e.g. DNA methylation clocks) and those serving as disease risk markers (e.g. markers of cardiovascular risk). While these categories have some overlap, it is important for the field to come to a consensus as to which category of biomarker should be measured at different stages of the research. For example, in an early phase trial of senolytics, measuring senescent cell burden may be sufficient but in a later phase trial, disease risk markers may be necessary. Omics data, which analyze biological systems on a molecular level, offer promising opportunities for identifying these biomarkers, yet significant hurdles remain such as lack of standardization with use of variable methodology, platforms, and protocols, reproducibility and lack of datasets for validation [59,60]. The lack of consensus on validated biomarkers complicates clinical trials, increasing their size and duration. Prioritizing biomarker standardization and their integration into regulatory frameworks would accelerate therapeutic development [61].

Trial design and regulatory acceptance are closely linked. Although preventive therapies for chronic diseases have been approved in the past, regulatory agencies have yet to receive similar compelling evidence for aging. Moving forward the provision of clearer guidance on trial design for aging preventative therapies and approval processes would encourage greater activity in gerotherapeutics [16]. Personalized treatment approaches and combination therapies will likely be necessary [62], adding complexity to the field but also expanding potential therapeutic strategies. While these factors present challenges, they are not insurmountable—many fields, including oncology and cardiology, have transitioned from broad early treatments to highly personalized and combinatorial approaches over time [63,64].

Lack of regulatory frameworks should be addressed in a multi-phase process going forward. Given the early stage of gerotherapeutic studies, the first step is reaching consensus on the design of early phase studies including intermediate outcomes and biomarkers followed by developing consensus on the design of later stage trials for efficacy and effectiveness. More information on trial design will come from the TAME trial and PROSPR program which occur in diverse settings, collect outcomes that are meaningful across systems such as resilience and multi-disease delay and are intentionally building tools that can be reused and adapted. Further, the development of core outcome measures and common data elements for geroscience studies would facilitate this, as done for other fields [65]. Finally, and in parallel, advocacy for inclusion of prevention for the maintenance of healthy aging and prolongation of healthspan as a formal target for gerotherapeutics is needed at regulatory bodies to avoid classifying aging as a disease. Support from national organizations such as the United States National Institute of Aging or internationally the WHO Clinical Consortium on Aging would greatly facilitate this.

In addition to regulatory and methodological challenges, economic barriers represent a significant challenge to the development of gerotherapeutics. The high cost of conducting clinical trials, combined with the financial risks associated with extended timelines, discourages investment in the field [66]. While some interventions for aging may require long-term studies to assess disease prevention or mortality outcomes, trial length ultimately depends on the selected endpoint and study design. Contrary to common assumptions, not all aging trials require extended follow-up periods. Some clinically meaningful endpoints, such as physical function, reversal of muscle loss and hospitalization, can be measured over shorter time frames and could support faster regulatory approval. The perception that aging trials must be long-term along with the lack of regulatory guidance on aging-related indications contributes to uncertainty, making investors hesitant to support these interventions [28]. Addressing these economic challenges will require targeted incentives, such as public-private partnerships (e.g., NIH’s Translational Geroscience Network), grant programs, and tax credits, to de-risk investment and foster innovation [35,36]. Models from oncology (e.g., Moonshot), rare diseases (e.g., Orphan Drug Act), and initiatives like the NIH’s Translational Geroscience Network demonstrate how targeted incentives and coordinated efforts can de-risk innovation. However, these approaches typically support disease-specific therapies and may not fully translate to gerotherapeutics, which target upstream aging processes and lack established regulatory or reimbursement pathways. Further while these solutions are widely discussed, meaningful implementation has been slow, leaving progress stagnant [35].

Public attitudes and limited policy engagement present additional barriers to advancing gerotherapeutics. Researchers have struggled to convey the potential of gerotherapeutics in a way that resonates with the public and policymakers, contributing to a lack of political will to support aging-related research [16]. Debates over whether aging should be classified as a disease further complicate this landscape, creating additional barriers to consensus [25]. Ethical concerns about lifespan extension, such as equitable benefits and resource allocation, have contributed to persistent doubts about the field and slowed policy development [48,49]. Economic inequality and limited access to healthcare providers or clinical trials, particularly among socioeconomically disadvantaged and racialized populations, could shape both the development and uptake of gerotherapeutics [16,17].

Public engagement and education campaigns that geroscience is fundamentally focused on preventing age-associated disease and reducing the burden of chronic conditions, with the goal of extending healthspan and promoting resilience in aging populations rather than merely prolonging life are essential [52]. These efforts must be coupled with strategies to address ethical concerns and position geroscience as a public health priority [33]. Important lessons from cancer prevention and vaccine promotion efforts can inform these efforts. Further, we must communicate how increased healthspan and delayed onset of multimorbidity could yield substantial cost savings to public healthcare systems, particularly by reducing hospitalizations and long-term care needs. Economic modeling and health services research will be important for quantifying the potential system-level benefits of gerotherapeutics and strengthening the value proposition for investment [41]. Clear, accessible, and tailored communication strategies will be required to foster public understanding and help align societal goals with advancements in geroscience. Tailoring could include education as to the importance of the difference between healthspan and lifespan to general audiences, cost saving for healthcare funders, reduced need for long-term care for healthcare planners, and improved participation of older individuals in the workforce and as volunteers to communities and employers. Further, engagement strategies with advocacy groups for older individuals such as AARP in the United States, CanAge in Canada and the International Federation of Aging, will be important for advancing the premise of geroscience.

Key strengths of this review include its comprehensiveness, the inclusion of grey literature and focus on the most recent and up-to-date literature. Limitations include the restriction to the English language literature, although this is unlikely to have significantly impacted the findings [67,68].

5. Conclusion

Geroscience has the potential to transform societal aging by extending healthspan and enhancing quality of life. Achieving these outcomes requires the establishment regulatory pathways for approving therapies directed at aging, sustainable funding, and public engagement. These barriers are interconnected but can be addressed through global collaboration to develop and harmonize regulatory frameworks, advancement of geroscience trial methodology and increased recognition of the value that healthy aging offers societies. Focused, coordinated action across these areas is essential to translate geroscience research into tangible benefits for aging societies worldwide.

CRediT authorship contribution statement

JM: Project lead, conceptualization, writing, review and final editing, CLS: methodology, writing- original draft preparation, reviewing and editing, JCN, YR, CM, ALL, RAM, GD, PK, BV: writing, review and editing.

Funding source

This work was supported by the Canadian Frailty Network.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Glossary

Geroprotectors or gerotherapeutics

interventions targeting molecular mechanisms involved in the aging process.

Geroscience

an interdisciplinary field dedicated to understanding the biological relationship between aging and age-related diseases.

Healthy Aging

“the process of developing and maintaining the functional ability that enables well-being in older age”.

Intrinsic Capacity

the sum of an individual’s physical and mental capacities.