Cellular Senescence and Senotherapeutics: The Expert Roundup

Future approaches may involve more precise targeting.

March 26, 2026

Cellular senescence, a state in which cells stop dividing but resist dying, accumulating in tissues over time, has emerged as one of the most promising targets in longevity medicine. Senescent cells actually serve important roles in development, wound healing, and cancer prevention, but as they accumulate with age or pathology, they become harmful: they secrete the senescence-associated secretory phenotype (SASP), a cocktail of pro-inflammatory factors, driving chronic inflammation, fibrosis, and tissue dysfunction, and “infecting” neighboring cells with senescence.

The seminal 2011 Baker et al. study showed that clearing senescent cells could extend healthspan in INK-ATTAC mice, giving rise to an entirely new therapeutic category. Since then, senolytics, which selectively kill senescent cells, and senomorphics, which modulate the SASP or reprogram senescent cells, have become major areas of research and investment.

The field is now transitioning from preclinical promise to clinical reality, with several companies advancing candidates into human trials across indications such as fibrosis, dermatology, and metabolic disease. However, significant challenges remain, including the lack of standardized biomarkers, the heterogeneity of senescent cell populations, and questions about safety and long-term efficacy. Some experts go as far as questioning the senescence paradigm itself. There have also been notable failures of senolytics in clinical trials, which has somewhat cooled down interest in the field.

Expert Perspectives on Senotherapeutics

We asked four leaders of senescence-focused biotech companies to discuss what drew them to the field, what makes their approaches unique, the obstacles they face on the path to the clinic, and what senotherapeutics might ultimately achieve for human health.

1. What do you find most compelling about senolytic/senomorphic therapies, and what convinced you that this path was worth pursuing seriously?

Marco Quarta, Co-Founder and CEO, Rubedo Life Sciences

What I find most compelling about senolytic and senomorphic therapies is their potential to address a root cause of aging. Cellular senescence is a causal driver of multiple chronic diseases, offering a rare medicinal opportunity to intervene upstream at a fundamental biological level rather than merely treating downstream symptoms.

My conviction grew from evidence showing how senescent cells actively orchestrate inflammation, fibrosis, and stem cell dysfunction. Recognizing that this biology is a major translational frontier led us to develop RLS-1496 at Rubedo. This first-in-class GPX4-modulating senotherapeutic emerged from ALEMBIC, our AI-driven multi-omics platform.

Seeing RLS-1496 progress into clinical trials across the U.S. and Europe has been the ultimate proof point. It transforms a fascinating scientific concept into a clinically actionable reality. For me, this confirms that the field is ready to move beyond discovery and into the lives of patients.

Lorna Harries, Professor of Molecular Genetics, University of Exeter; Founder, SENISCA

I first started thinking seriously about senescence as a drug target when the data emerged from the initial INK-ATTAC mouse studies. Until then, although there was evidence that these cells were deleterious, conclusive proof that they were drivers of aging rather than passengers was lacking. The work showing that removal of senescent cells improved functionality in multiple organ systems was very persuasive.

Going after the underpinning mechanisms of age-related disease rather than dealing with endpoint consequences is a much more efficient approach to medicine. At the moment, we patch up the consequences of ongoing disease after the event. Because the diseases of aging have common roots, many older people live with several chronic conditions and end up taking multiple drugs that can interact. Treatment is often delivered long after symptom onset, whereas an earlier, more proactive approach would allow us to reduce the drug burden on patients.

Robin Mansukhani, CEO, Deciduous Therapeutics

Senescent cells are a compelling area for novel therapies because they are an upstream, multi-indication target. Senescent cells commonly express multiple fibrotic and inflammatory pathways, whereas most therapies target only a single pathway. Our data supports senescence as a master regulator in both metabolic and fibrotic diseases.

Moreover, in the context of aging, most patients will have senescence-driven comorbidities. Systemically ablating senescent cells can have multi-indication impacts. Finally, with anti-senescence approaches, a single treatment often has durable effects lasting several months or more. Taken together, we believe an effective and safe anti-senescence approach could be revolutionary.

Adam Freund, Co-Founder and CEO, Arda Therapeutics

What I find most compelling isn’t the ‘senescence’ label, but the clinical power of targeted cell depletion. We’ve seen this work with B cells in autoimmunity, eosinophils in asthma, and myeloid cells in GvHD. If these relatively coarse strategies are effective, then a more targeted approach – the precise removal of only the most pathogenic cell states – likely represents a powerful therapeutic strategy that can be applied across multiple diseases and cell types.

2. How is your company unique in the senescence landscape – what is your technical approach, and why was it chosen?

Marco Quarta

Rubedo is unique because we rejected the idea of senescence as a monolith. Senescent cells are heterogeneous and context-dependent; they are only meaningfully druggable if you understand their specific vulnerabilities. Our philosophy is precision senotherapeutics: identifying functional dependencies and designing selective therapies matched to specific disease biology.

Our technical edge lies in ALEMBIC, which resolves cell heterogeneity at high resolution. This platform allowed us to identify GPX4-related biology as a critical vulnerability in certain senescent states. By focusing on how these stress-adapted cells survive, we can disrupt them with surgical precision.

Lorna Harries

I think our work is quite different from other players in the space. We were among the first academic teams to demonstrate that senescence was not irreversible and have been researching the underpinning biology of the systems we are targeting in an academic setting for decades. This has allowed us to identify a novel and unique point of traction that works with the cells’ own biology.

We have a unique single-gene reprogramming approach that works with the underpinning biology of the genes in question to restore their natural, endogenously regulated gene expression. It’s not an overexpression or a knockdown of genes involved in senescence; it’s a resetting of the cell’s ability to properly regulate them.

Robin Mansukhani

It is well understood that an effective immune system can quickly recognize and ablate senescent cells. However, this immune function – specifically that of iNKT cells – becomes compromised over time. We did the heavy lifting to understand which immune cells (Natural Killer T cells) were responsible for senescence removal. Subsequently, we designed a novel small molecule that specifically restores NKT function, leading to single-dose disease efficacy in metabolic and fibrotic diseases.

Adam Freund

Most companies in the senescence space are built on a “senescence-first” hypothesis: starting with senescent cell markers and then searching for diseases where those markers are expressed. However, Arda’s approach is fundamentally “disease-first.” Rather than searching for senescent cells, Arda’s platform identifies and targets disease-driving cell states, irrespective of their relationship to traditional senescence markers.

3. What is your strategy for bringing your therapy to the clinic, including target indications and work with partners and regulators?

Marco Quarta

Our strategy focuses on indications where senescence is measurable and clearly pathogenic, such as dermatology and fibrotic disease. For RLS-1496, we utilized a unique design, skipping healthy volunteers to test the drug directly on various patient groups in a “basket trial.” By testing both chronic skin lesions and healthy skin, we are simultaneously evaluating effects on disease and skin aging.

Lorna Harries

Our technology has the potential to impact multiple age-related diseases and beyond. We are developing oligonucleotide therapeutics for aging diseases, starting with idiopathic pulmonary fibrosis (IPF) due to its clear association with senescence. The barrier is not whether the drug works, but how we can efficiently deliver it. Oligonucleotides have advantages over conventional small molecules in precision and safety.

Robin Mansukhani

We focus on senescence-driven indications such as lung fibrosis and various metabolic diseases. Our goal is to demonstrate significant improvement over the current standard of care in specific disease indications. We plan to collect multiple disease readouts in our first clinical studies.

Adam Freund

We are pursuing precision cell depletion across multiple inflammatory and immunological indications, with an initial focus on fibrosis. Each program is optimized for its specific disease context, including target selection, molecule design, and clinical and regulatory strategy.

4. How close do you think we are to seeing multiple approved senolytic/senomorphic therapies, and what most limits the pace of progress today?

Marco Quarta

We are significantly closer to approved therapies than we were even three years ago. The shift from “conceptual excitement” to “mechanical execution” is evident. However, the pace is still limited by translational complexity, as senescence manifests differently across tissues and disease stages.

Lorna Harries

We are still some way off, but more early entries into the clinic are emerging. A major hindrance is the lack of validated biomarkers linking senescent cell reduction to main disease outcomes in trials.

Robin Mansukhani

The primary bottleneck is safety. Many senolytic therapies come from repurposed cancer drugs and have narrow therapeutic windows. However, newer next-generation therapies exhibit cleaner safety profiles, which will help facilitate early proof of concept.

Adam Freund

We are far from seeing a wave of approvals. The field is bottlenecked by a focus on a narrow “senescence-first” framework. Until the field moves towards a more encompassing understanding of specific pathology, significant translational failures are likely to continue.

5. What do you expect senolytic/senomorphic therapies will be able to do for humans in the short and long term?

Marco Quarta

In the short term, I expect senotherapeutics will show immense value in treating diseases like fibrosis, chronic inflammation, and metabolic disorders. In the long term, we envision a preventive medical paradigm that allows us to delay or attenuate age-related conditions by targeting biomarkers related to cellular senescence.

Lorna Harries

These approaches could be transformational, offering better options for specific age-related diseases. If successful, early treatment could delay the onset of subsequent diseases, significantly reducing healthcare costs and improving quality of life.

Robin Mansukhani

I believe that with strong safety and efficacy profiles, anti-senescence therapies will be revolutionary and widely adopted, providing single-agent therapies with multi-indication impacts.

Adam Freund

In the long term, success will look like a suite of highly specific, cell-centric therapies designed to deplete exactly pathogenic populations driving diseases, rather than a single drug addressing all senescent cells.

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About the Author

Arkadi Mazin is a seasoned journalist and op-ed author with a passion for learning and exploration. His interests span from politics to science and philosophy. Having studied economics and international relations, he is particularly interested in the social aspects of longevity and life extension. He strongly believes that life extension is an achievable and noble goal that has yet to take its rightful place at the very top of our civilization’s agenda – a situation he is eager to change.

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  • Latest Research in Longevity
  • Advancements in Senotherapeutics
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