Cellular senescence network SenNet publishes first comprehensive Human Senescence Atlas

When the NIH Cellular Senescence Network (SenNet) published the first comprehensive Human Senescence Atlas on the cover of Cell in June 2026, it marked more than another milestone in aging research.

It fundamentally changed how scientists and the nutrition industry understand cellular senescence. For years, senescent cells have been viewed as a single biological target. SenNet challenges that assumption.

By integrating single-cell sequencing, spatial multi-omics and AI-driven analysis across multiple human tissues, the consortium revealed that senescent cells differ markedly depending on where they reside.

Their molecular signatures, biological behaviors, and surrounding microenvironments vary from tissue to tissue, leading researchers to introduce the concept of distinct tissue-specific senotypes.¹

The significance of the atlas extends far beyond academic research. It suggests that healthy-aging interventions can no longer rely on the broad premise of clearing senescent cells. Future solutions will increasingly be judged by whether they target the right senescent cells in the right tissues.

For formulators and ingredient developers, SenNet signals the beginning of a new era: precision senescence.

A more precise view of cellular senescence – and the rise of senotypes

Cellular senescence is a natural protective mechanism. When cells accumulate excessive damage, they permanently stop dividing, preventing potentially harmful cells from proliferating. However, as immune surveillance declines with age, these senescent cells accumulate instead of being efficiently removed.

The result is the persistent release of pro-inflammatory factors collectively known as the senescence-associated secretory phenotype (SASP), contributing to chronic low-grade inflammation – or inflammaging – that has been linked to numerous age-related conditions.

This fundamental biology has been recognized for years. What SenNet changes is the level of precision.

Rather than treating senescent cells as one homogeneous population, the atlas demonstrates that senescent cells involved in skeletal muscle decline, vascular dysfunction, joint degeneration, or cognitive aging are biologically distinct. SenNet explicitly proposes that future interventions should be developed around tissue-specific senotypes rather than relying on universal senolytic strategies.¹

For the nutrition industry, this represents an important strategic shift. Broad anti-aging claims centered on cellular senescence support are likely to become less compelling. Instead, future healthy-aging products will increasingly require tissue-specific positioning supported by mechanistic evidence and physiological outcomes.

This raises an important question for ingredient developers: which natural ingredients are best positioned for this new direction? Increasingly, that question points to one botanical in particular: fisetin.

Why fisetin has become the benchmark natural senolytic

Over the past decade, researchers have evaluated numerous senolytic candidates, ranging from pharmaceutical compounds such as dasatinib and navitoclax to naturally occurring flavonoids including quercetin, piperlongumine, and fisetin. While many demonstrated senolytic activity under specific experimental conditions, relatively few combined efficacy, safety, and translational potential suitable for nutritional applications.

A major turning point came in 2018, when researchers led by the Mayo Clinic systematically screened ten naturally occurring flavonoids for senolytic activity. Published in eBioMedicine, the study identified fisetin as the most effective natural senolytic evaluated, demonstrating selective clearance of senescent cells while extending both healthspan and lifespan in aged and prematurely aged mice.³

Bar chart from the 2018 Mayo Clinic study ranking fisetin as the most effective natural senolytic among ten flavonoids for clearing senescent cells

Fisetin’s position has been built gradually – not on a single landmark study, but on years of accumulating evidence.

Over the past eight years, research has expanded across multiple experimental models, consistently showing that fisetin influences several interconnected features of cellular senescence, including senescent cell survival pathways, inflammatory signaling, and cellular stress responses. Rather than relying on isolated findings, fisetin has gradually built one of the most comprehensive evidence bases among naturally derived senolytic ingredients.

That growing body of evidence places fisetin in a strong position as the field moves toward precision senescence.

Muscle ageing and sarcopenia: The first blueprint for precision senolytics

If SenNet provides the roadmap for tissue-specific senescence, skeletal muscle is one of the first tissues where that roadmap is beginning to translate into practical evidence.

Loss of muscle function, or sarcopenia, is closely associated with frailty, mobility decline, and loss of independence, making healthy muscle aging one of the fastest-growing areas within the longevity nutrition market.

In 2025, researchers from the University of Colorado Boulder and the National Institute on Aging published a study in Aging Cell comparing intermittent fisetin supplementation with both genetically engineered senescent-cell clearance and the pharmaceutical senolytic ABT-263.⁴

In naturally aged mice, fisetin produced comparable improvements in grip strength and frailty scores while reducing markers of cellular senescence within skeletal muscle. Notably, no comparable benefits were observed in young healthy animals, supporting the hypothesis that fisetin acts through senescence-related mechanisms rather than serving as a general performance enhancer.

Earlier cell-based studies have reported similar protective effects in aging skeletal muscle models exposed to oxidative stress.⁵⁻⁶

Although current evidence remains limited to preclinical studies, it illustrates the direction SenNet envisions: evaluating senolytics according to specific tissues, biological pathways, and measurable functional outcomes rather than broad anti-aging claims alone.

Building the benchmark for natural senolytic ingredients

As senolytics transition from an emerging research concept into a defined ingredient category, expectations are rising across every dimension of product development. Demonstrating senolytic activity is no longer enough.

Increasingly, ingredient suppliers are expected to provide a complete scientific foundation – from tissue-specific validation and human clinical evidence to manufacturing quality, regulatory readiness, and long-term research commitment.

This broader shift reflects the direction SenNet has established for the field. As healthy-aging science moves toward precision senescence, the ingredients most likely to succeed will be those supported not only by compelling mechanisms, but also by evidence that connects specific tissues with measurable physiological outcomes.

BeFisetin® was developed with this long-term vision in mind.

Bonerge’s research strategy has evolved alongside this shift toward precision senescence. BeFisetin has completed two randomized human clinical studies, including one specifically designed to evaluate intestinal cellular senescence – an area that closely aligns with SenNet’s emphasis on tissue-specific senotypes.

Rather than treating senescence as a single systemic process, this research strategy reflects a growing recognition that different tissues require different evidence.

Scientific validation, however, is only one part of the equation. For ingredient developers, credibility also depends on whether that science can be translated into consistent manufacturing quality and regulatory confidence.

BeFisetin is built on quality, regulatory, and clinical readiness:

≥98% fisetin content, from a fully traceable botanical source and verified against certified reference standards
The only fisetin ingredient with Self-Affirmed GRAS status
FDA GRAS and New Dietary Ingredient (NDI) submissions underway to support broader commercialization
Additional human clinical studies in progress to expand tissue-specific evidence across future healthy-aging applications

Rather than pursuing a single product claim, Bonerge’s objective is to help establish the scientific benchmark for the next generation of natural senolytic ingredients – where tissue-specific clinical evidence, verified quality, and regulatory preparedness together define long-term credibility.

Preparing for the precision senescence era

The publication of the Human Senescence Atlas represents more than a scientific achievement – it provides a new roadmap for healthy-aging innovation.

Instead of asking whether an ingredient can target senescent cells, formulators will increasingly ask which senescent cells, in which tissues, and with what functional outcomes.

That transition favors ingredients supported by tissue-specific evidence rather than broad anti-aging narratives. It also raises expectations for ingredient quality, regulatory readiness, and clinical validation.

Fisetin’s evolution over the past eight years – from a promising natural flavonoid to one of the most extensively studied natural senolytic candidates – offers an early glimpse of where the category is heading.

As precision senescence evolves from an emerging scientific concept into a product development framework, ingredients supported by tissue-specific evidence, rigorous clinical validation and robust quality systems will be best positioned to define the next generation of healthy-aging innovation.

Bonerge is committed to helping formulators accelerate that transition through BeFisetin, supported by technical dossiers, clinical data and formulation expertise.

Find out about BeFisetin here.

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