From Network-Based Drug Discovery to Wellspan: Reframing the Goals of Longevity Medicine
In dialogue with: Andriy Yabluchanskiy and Mykola Iabluchanskyi. Ceiling of Life: Between the Dream of Immortality and the Risk of Wasted Years. 2025.
A recent network-medicine study by Gross and colleagues proposes a systematic strategy for identifying existing drugs that could be repurposed to influence biological mechanisms associated with aging. Its central contribution is methodological: aging is approached not as one pathway, one gene, or one disease, but as an interconnected network of biological processes.
This is an important step for geroscience. But it also brings into focus a question that molecular analysis cannot answer by itself: What should count as success when we intervene in the biology of aging?
The answer cannot be lifespan alone. Nor is healthspan, although indispensable, sufficient. The ultimate outcome of longevity medicine should be wellspan: the period during which a person remains present in their own life — capable of agency, relationship, participation, meaning, and continuity of self.
The network study offers an instrument for finding possible interventions. The concept of wellspan offers the criterion by which their value should eventually be judged.
What the Study Proposes
Gross and colleagues begin from a familiar difficulty in aging research. Thousands of genes have been associated with longevity, age-related disease, or biological processes involved in aging. Yet effective interventions that can safely and reliably alter aging trajectories in humans remain elusive.
One reason is that aging is multifactorial. Genomic instability, mitochondrial dysfunction, cellular senescence, altered intercellular communication, disturbed nutrient sensing, loss of proteostasis, telomere attrition, impaired autophagy, stem-cell exhaustion, extracellular-matrix changes, and epigenetic alterations do not operate as isolated entities. They overlap, interact, compensate for one another, and can amplify one another.
The study therefore maps 2,358 longevity-associated genes onto the human protein-interaction network. It identifies gene clusters associated with particular hallmarks of aging and shows that these clusters form distinct but interconnected biological modules. Together, these modules constitute a broader “longevity network.”
This matters because a drug does not need to target one aging-associated gene directly to have an effect on aging biology. It may act through neighboring targets, downstream pathways, or network-level interactions. The authors use this principle to screen 6,442 approved or experimental compounds for their proximity to hallmark modules.
They then add a second measure: pAGE, a transcription-based indicator intended to assess whether a drug-induced expression profile tends to counteract or reinforce age-associated gene-expression changes. A compound may be close to an aging-related network yet still push it in a potentially harmful direction. Network proximity identifies the potential for influence; pAGE attempts to estimate its direction.
The result is a drug-prioritization framework called SHARP — systematic hallmark-based aging repurposing. Its purpose is not to announce an anti-aging cure. Its purpose is to generate more plausible, testable, and biologically interpretable candidates for further study.
What the Study Does Not Prove
The distinction between a candidate and a treatment is essential.
The study does not show that its prioritized compounds extend human lifespan. It does not show that they extend healthspan. It does not establish that they preserve cognition, mobility, independence, or quality of life. It does not settle questions of dose, timing, duration, tissue specificity, drug interactions, long-term safety, affordability, or unequal access.
It offers a computational and systems-biological way to select hypotheses.
This is not a weakness of the study. It is the proper role of a discovery framework. But this limitation must remain visible, particularly in a field where the language of “anti-aging” is easily transformed into commercial promise long before clinical proof exists.
A molecular signature is not a person. A favourable gene-expression change is not yet a favourable life outcome. A drug that improves one hallmark may worsen another. A compound that helps one organ system may harm another. A therapy that delays mortality can still increase treatment burden, frailty, dependency, or cognitive decline.
Therefore, the scientific path must remain sequential:
First, identify a plausible molecular target.
Then demonstrate a consistent biological effect.
Then establish safety and tissue-specific consequences.
Then test functional outcomes in organisms and humans.
Finally, determine whether the intervention improves the lived course of life.
The final step is where longevity science becomes medicine.
A Necessary Corrective Framework
The purpose of this commentary is not to oppose the network-medicine approach. On the contrary, its recognition that aging is multicausal, networked, and resistant to single-target solutions is an important advance. The study gives geroscience a more refined way to formulate and prioritize molecular hypotheses.
But every powerful method needs an explicit framework of correction. A network score, a transcriptomic reversal, or a positive pAGE value may identify a biologically plausible candidate; none of these outcomes alone can determine whether the intervention improves the life of the person who receives it. The missing corrective questions are therefore clinical, ethical, and existential — not because they are less scientific, but because they define what medical success means.
Before a proposed gerotherapeutic is presented as beneficial, researchers, clinicians, regulators, and funders should ask:
What is being extended? Is the intervention expected to extend survival, disease-free time, functional capacity, or the period of meaningful self-directed life?
For whom does it work? Do effects differ by age, sex, genetic profile, multimorbidity, frailty, socioeconomic circumstances, or baseline functional reserve?
At what cost? What are the risks of adverse effects, cancer promotion or suppression, metabolic disturbance, neuropsychiatric effects, polypharmacy, burdensome monitoring, and drug interactions?
In which tissues and over what duration? Could a molecular effect that appears favourable in one cell type or organ produce harm elsewhere or after long exposure?
Does it compress or extend morbidity? Does the intervention shorten the period of disability before death, or does it prolong survival while increasing dependency, frailty, and medical burden?
Does it preserve wellspan? Does the person retain mobility, cognition, communication, decision-making capacity, social connection, purpose, and the ability to recognize their life as their own?
Who has access? Will an intervention widen disparities by becoming available only to affluent populations while more basic conditions of healthy aging remain unmet?
Who defines benefit? Are older adults, people living with chronic disease, and caregivers involved in defining the outcomes that matter?
These questions do not weaken the molecular project. They protect it from premature interpretation and from a reduction of medicine to measurable biological change alone. A drug-repurposing framework is most valuable when it is embedded in a clinical pathway that examines target engagement, organism-level function, real-world safety, functional independence, patient-reported outcomes, and the preservation of wellspan.
The correction proposed by Ceiling of Life is therefore simple: every attempt to extend lifespan should be assessed simultaneously for its effects on healthspan and wellspan. An intervention that adds years while diminishing autonomy, meaning, cognition, or relational life may lengthen biological existence but fail the more demanding test of human benefit.
Three Measures of Aging
A central problem in public discussion of aging is that several different realities are compressed into one word: longevity.
The first is lifespan: the total duration of biological life, from birth until death.
The second is healthspan: the period in which disease, disability, and ongoing medical dependence do not substantially determine daily life. It is the interval in which health remains sufficiently intact that the body is not the main obstacle to living.
The third is wellspan: the period in which a person remains recognizably themselves, even if disease is present. Wellspan includes the ability to make meaningful choices, sustain relationships, participate in society, preserve a sense of identity, and experience one’s life as one’s own.
These three measures often diverge.
A person may live longer without remaining healthy. A person may be chronically ill while still living with autonomy, dignity, and meaning. Another person may remain biologically alive after cognition, communication, mobility, and self-determination have profoundly deteriorated.
Therefore, lifespan alone is an incomplete outcome. It tells us that the organism has survived. It does not tell us whether the person has been able to live.
Why Healthspan Is Necessary but Not Enough
Healthspan is rightly becoming a central objective of geroscience. Preventing cardiovascular disease, diabetes, cancer, stroke, dementia, frailty, falls, disability, sensory loss, and functional decline can transform the experience of aging.
But healthspan is not the full measure of a life.
Many people live well with chronic disease. A person with hypertension, diabetes, an implanted pacemaker, a prosthetic joint, an insulin pump, renal impairment, or a previous myocardial infarction may retain strong agency, social connection, intellectual activity, work, creativity, family life, and a clear sense of personal identity.
Such a person may no longer be in perfect health, but may still possess substantial wellspan.
This is why medicine should not divide people simplistically into “healthy” and “diseased.” Health and disease coexist within the same person, often throughout life. The task of medicine is not only to remove disease — frequently an impossible goal — but to guide its course so that it does the least possible harm to function, autonomy, and meaningful participation.
In this sense, treatment is successful not only when it normalizes a laboratory value or prevents death. It is successful when it helps preserve the person.
The Risk of Longer but Emptier Life
The dream of longevity contains a hidden danger. If medicine focuses only on prolonging biological survival, it may create more years without creating more life.
Modern medicine has become remarkably skilled at supporting failing organs, replacing joints, implanting devices, controlling blood pressure and glucose, treating infections, restoring circulation, prolonging ventilation, and sustaining bodily processes under conditions that would previously have led quickly to death.
These achievements are real and valuable. But they have also enlarged a difficult territory: years in which the body survives while mobility, cognition, communication, independence, and personal continuity diminish.
The greatest risk is not age itself. Old age can contain wisdom, affection, time for reflection, freedom from earlier pressures, intergenerational connection, and new forms of contribution.
The risk is a prolonged final period in which a person is alive but increasingly absent from their own life: unable to decide, unable to communicate, unable to recognize loved ones, unable to remain connected to the values and relationships that once constituted their identity.
This is the gap between lifespan and wellspan.
A society that celebrates survival without asking what kind of life is being preserved may mistake biological persistence for human success.
From Network Biology to Human Outcomes
The network-medicine framework can become more clinically powerful when it is linked to a hierarchy of outcomes.
The first level is where network science is strongest. The final level is where geroscience must arrive if it is to justify its promises.
A therapy should not be judged only by whether it alters molecular pathways associated with aging. It should be judged by whether it helps people preserve the capacities that make time valuable: walking, thinking, remembering, communicating, choosing, loving, working, creating, and belonging.
A Research Agenda for Wellspan
If wellspan becomes an explicit goal, it changes the design of longevity research.
Clinical trials should measure not merely mortality and biomarkers, but also:
Physical function, gait speed, strength, balance, endurance, and fall risk.
Cognitive function, memory, executive capacity, communication, and preservation of independence.
Frailty, multimorbidity, hospitalization, institutionalization, and treatment burden.
Sensory function, including hearing and vision, because sensory loss can accelerate social withdrawal and cognitive decline.
Pain, sleep, fatigue, mood, and symptom burden.
Capacity for self-care and participation in daily activities.
Social connection, loneliness, caregiving needs, and community participation.
Patient-reported outcomes: whether people feel their lives remain meaningful and recognizably their own.
This does not reduce scientific rigor. It strengthens it. A molecular intervention that cannot demonstrate benefit at the level of lived function may be biologically interesting, but it has not yet demonstrated its full medical value.
The same principle applies to safety. An intervention that lengthens life but creates severe adverse effects, increases polypharmacy, worsens confusion, reduces mobility, or imposes an exhausting treatment regimen may shorten wellspan even if it extends survival.
The Proper Ambition of Geroscience
The proper ambition of geroscience is not immortality.
Nor is it simply the extension of average lifespan, maximum lifespan, or time until death. These numbers matter, but they are not enough.
The proper ambition is to reduce the gap between the years biology makes possible and the years people can live as active subjects of their own lives.
This means preventing premature death where possible. It means extending healthspan through prevention, treatment, rehabilitation, and social support. It also means preserving wellspan when healthspan has ended — helping people remain autonomous, connected, and meaningful even in the presence of chronic disease.
Network-based drug discovery may become an important contributor to this project. It can identify promising molecular routes, reveal connections among mechanisms of aging, and speed the selection of compounds for rigorous testing.
But it cannot determine the final goal on its own.
That goal must remain human: not merely longer survival, but longer life in the fullest sense — life in which the person remains present, capable of relation, capable of choice, and capable of recognizing the time they have been given as their own.
You can learn more by reading our e-book or listening to our audiobook
Andriy Yabluchanskiy together with Mykola Iabluchanskyi
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