#1

In a provocative new manifesto, leading biogerontologists David Gems and João Pedro de Magalhães attack the politically safe slogan that has come to dominate aging research: “We want to extend healthspan, not lifespan.” The authors argue this distinction is not only scientifically incoherent but ethically flawed. The central thesis is that aging is the cause of late-life disease; therefore, any intervention potent enough to genuinely delay pathology (extend healthspan) will inevitably delay death (extend lifespan).

The report contends that the “Healthspan Only” narrative is a defensive crouch adopted by researchers to avoid being labeled as charlatans or immortality-seekers. However, this cowardice creates a “false dichotomy” between aging and disease. Using the “One Hoss Shay” analogy (dying instantly in perfect health), they show that while compression of morbidity is the ideal, it is biologically implausible to arrest disease without pushing back the wall of mortality. The authors call for a paradigm shift: Biogerontology must explicitly reclaim the goal of life extension, framing it correctly as “saving lives” by delaying the lethal onset of senescence, just as oncology saves lives by delaying cancer death.

Open Access Paper: Against “Extending Healthspan but Not Lifespan” as a Goal for Biogerontology
Institution: Institute of Healthy Ageing, University College London (UK); University of Birmingham (UK).
Journal: Preprints.org (Preprint Repository).
Impact Evaluation: The impact score of this journal is N/A (Preprint Server), evaluated against a typical high-end range of 30–60+ (e.g., Nature, Cell). Therefore, this is a Non-Rated source, but relies entirely on the high authority of the authors (David Gems and João Pedro de Magalhães are elite figures in the field with h-indices >80).

Part 2: The Biohacker Analysis

Mechanistic Deep Dive

The authors dismantle the current “Geroscience” consensus through two key mechanistic lenses:

  1. The Aging-Disease Continuum: They argue that “aging” and “age-related disease” are the same biological phenomenon. You cannot treat the cause of heart disease, cancer, and Alzheimer’s (senescence) without extending the organism’s survival.
  2. Hyperfunction & Trade-offs: Drawing on Gems’ previous work on Hyperfunction Theory and Magalhães’ Tumor Suppression Theory, the paper suggests that the mechanisms killing us are often extensions of developmental programs.
  3. The Fraud of “Compressed Morbidity”: They critique the idea that we can simply keep people healthy until 85 and then have them drop dead instantly (“One Hoss Shay”). Current data suggests that while we can delay onset, the period of senescence often shifts with lifespan.
  • Organ Priority: The paper implies that systemic interventions (targeting insulin/IGF-1, mTOR) are necessary, rather than organ-specific “band-aids” which characterize Geriatric Medicine (as opposed to Biogerontology).

Novelty

  • Political Incorrectness: It openly challenges the funding strategy of the NIA and major nonprofits which explicitly forbid “life extension” as a stated goal.
  • Reunification: It formally attempts to merge the distinct goals of Geriatric Medicine (managing decline) and Biogerontology (altering the rate of aging), arguing that keeping them separate has stalled progress.

Critical Limitations

  • No New Data: This is a philosophy of science paper, not an experimental study. It offers no new molecules or trial results.
  • Speculative Ethics: The argument assumes that “saving lives” (life extension) is universally regarded as positive, glossing over the significant socioeconomic anxieties (overpopulation, inequality) that drive the “Healthspan Only” narrative.
  • Translational Gap: While logically sound, the paper does not offer a roadmap for how to get the FDA to approve a “Life Extension” endpoint, which is the primary regulatory hurdle forcing companies to use “Healthspan” proxies.

Part 4: The Strategic FAQ

  1. Q: If I only care about feeling good (Healthspan), why should I care about Lifespan extension?

    • A: Because you can’t have one without the other. The paper argues that “pure” healthspan extension (squaring the curve without moving the end point) is largely a myth. If you successfully slow aging, you will live longer. If you aren’t living longer, you likely haven’t slowed aging.

  2. Q: Isn’t “Life Extension” just for eccentric billionaires?

    • A: The authors frame it as “Saving Lives.” Just as we don’t consider heart surgery “for billionaires only,” treating the root cause of death (aging) is a humanitarian imperative.

  3. Q: Does the FDA recognize “Lifespan” as an endpoint?

    • A: No. This is perhaps part of the problem. You currently must target a specific disease (e.g., TAME Trial targeting diabetes/comorbidities) to get approval, forcing companies to play the “Healthspan” game.

  4. Q: What specific drugs do the authors implicitly endorse?

    • A: They reference the NIA ITP, which points directly to Rapamycin, Acarbose, and 17-alpha Estradiol as the only reproducible lifespan extenders in mammals.

  5. Q: Is “Compression of Morbidity” impossible?

    • A: Not impossible, but the authors suggest it’s rare. Usually, life extension stretches the entire timeline—youth, middle age, and decline. You might be frail for longer in absolute years, but less frail relative to your age.

  6. Q: What is the “One Hoss Shay” reference?

    • A: It’s a poem about a carriage built so perfectly it lasted 100 years and then fell apart all at once. It is the idealized (and likely unrealistic) model of “Healthspan only” where you die instantly without prior sickness.

  7. Q: Are there conflicts with Metformin?

    • A: Potentially. While Metformin is the poster child for “Healthspan” (TAME trial), the ITP failed to show lifespan extension in mice with Metformin alone. This paper’s logic would downgrade Metformin compared to Rapamycin.
3 Likes
#2

I agree that almost universally things that improve healthspan will increase lifespan.

One possible area where I’m not seeing this is female HRT, I typically state that this is something that for most women improves quality of life, but I don’t have evidence yet for life extension.

There are a bunch of things that improve quality of life that shorten lifespan, but they don’t truly increase healthspan (for example overdoing growth hormone and TRT might make one’s quality of life seem better for some people, but will decrease healthspan ultimately).

4 Likes
#3

Yes - while I generally agree with the paper, I would also say there are edge cases that might increase healthspan or quality of life, perhaps Growth Horming / IGF-1 for men, but potential even shorten lifespan. These might be rational decisions (to dose with these compounds) to make, for some responders.

1 Like
#4

Aging is not age related disease.

Age related disease is a measure disease over time.

Idade is a measurement of time.

Aging is disease with age (time) without an exposure.

A disease with age with an exposure, is not aging.

Therefore vast majority of cases of atherosclerotic heart disease is not caused by aging, it’s caused primarily by LDL-C/APOB, diabetes, hypertension, etc, exposures.

People are still living in the 90’s without understanding powerful recent mendelian randomization studies showing true causes of age-related disease: whether it is from aging, or an exposure.

1 Like
#5

@A_User , you seem to be denying the “Geroscience Hypothesis” - or am I wrong here?

The Geroscience Hypothesis

The Geroscience Hypothesis posits that fundamental biological aging processes are the primary root cause of most chronic pathologies. It argues that aging is not merely a passive decline, but a modifiable risk factor. Therefore, therapeutically targeting the underlying mechanisms of aging will simultaneously delay the onset and severity of multiple age-related comorbidities (e.g., cardiovascular disease, cancer, Alzheimer’s) more effectively than treating each disease in isolation.

This framework shifts medicine from a reactive “whack-a-mole” approach—treating specific diseases after diagnosis—to a systemic, preventative paradigm. The hypothesis relies on manipulating the Hallmarks of Aging, which include:

  • Genomic Instability: Accumulation of DNA damage.
  • Cellular Senescence: Accumulation of “zombie” cells that secrete inflammatory factors (SASP).
  • Mitochondrial Dysfunction: Loss of cellular energy efficiency.
  • Loss of Proteostasis: Failure in protein maintenance and clearance.

The clinical goal is the compression of morbidity : extending healthspan (the period of life spent in good health) so that physical decline is confined to a short period immediately preceding death, rather than a prolonged period of frailty.

Sources:

#6

That’s too vague, which chronic pathologies and under what time period?

Aging is not causing the vast majority of ASCVD people have today. See any mendelian randomization study published in NEJM, The Lancet, Nature, etc, on HMGCR or PCSK9 targets. Targeting these is not targeting aging.

But I do believe in aging causing ASCVD that does not look like the cases we have today. Those same processes might be causing other diseases at the same time.

#7

No one ever died of good health.