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Naked mole-rat

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categories: ["longevity", "foundations"]

categories: ["longevity", "foundations"]

tags: ["aging", "comparative biology", "cancer resistance", "model organism", "mortality", "biogerontology"]

tags: ["aging", "comparative biology", "cancer resistance", "model organism", "mortality", "biogerontology"]

summary: "A small eusocial African rodent whose flat mortality curve, tumour resistance and anoxia tolerance make it comparative biogerontology's central model organism."

summary: "A small eusocial African rodent whose flat mortality curve, tumour resistance and anoxia tolerance make it comparative biogerontology's central model organism."

updated: "2026-08-23"

updated: "2026-10-29"

humanEvidence: "No naked mole-rat-derived intervention has been tested in people; the only lifespan result outside the species is in transgenic mice."

humanEvidence: "No naked mole-rat-derived intervention has been tested in people; the only lifespan result outside the species is in transgenic mice."

---

---

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"rows": [

"rows": [

{ "label": "Species", "value": "Heterocephalus glaber" },

{ "label": "Species", "value": "Heterocephalus glaber" },

{ "label": "Native range", "value": "Horn of Africa" },

{ "label": "Native range", "value": "Horn of Africa" },

{ "label": "Adult mass", "value": "30–40 g" },

{ "label": "Adult mass", "value": "30-40 g" },

{ "label": "Max lifespan", "value": ">30 years, captive" },

{ "label": "Max lifespan", "value": ">30 years, captive" },

{ "label": "Social structure", "value": "Eusocial, one breeding female" },

{ "label": "Social structure", "value": "Eusocial, one breeding female" },

{ "label": "Notable traits", "value": "Tumour resistance, anoxia tolerance" },

{ "label": "Notable traits", "value": "Tumour resistance, anoxia tolerance" },

lines 28–39 → 28–394 unchanged lines not shown

```

```

**The naked mole-rat** (*Heterocephalus glaber*) is a small subterranean rodent of the Horn of

**The naked mole-rat** (*Heterocephalus glaber*) is a small subterranean rodent of the Horn of

Africa that serves as comparative biogerontology's central example of

Africa and comparative biogerontology's central example of

[[negligible-senescence|negligible senescence]] — a mammal whose measured risk of dying does not

[[negligible-senescence|negligible senescence]]: a mammal whose measured risk of dying does not

climb with age. It lives roughly ten times longer than a mouse of similar size, resists spontaneous

climb with age. It lives roughly ten times longer than a mouse of similar size, resists spontaneous

tumours, and survives oxygen deprivation that kills other mammals within minutes. Each of those

tumours, and survives oxygen deprivation that kills other mammals within minutes. Each of those

traits has a proposed mechanism and a body of laboratory work behind it. None has yet produced an

traits has a proposed mechanism and a body of laboratory work behind it, but none has yet produced

intervention tested in people.

an intervention tested in people.

## The animal

## The animal

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colonies of tens to a few hundred animals. They are eusocial: a single female breeds, and the rest

colonies of tens to a few hundred animals. They are eusocial: a single female breeds, and the rest

of the colony is reproductively suppressed and divided into castes that dig, forage and defend.

of the colony is reproductively suppressed and divided into castes that dig, forage and defend.

Jennifer Jarvis described the arrangement in 1981, the first time eusociality had been documented

Jennifer Jarvis described the arrangement in 1981, the first time eusociality had been documented

in a mammal.[^jarvis1981] They are hairless, effectively blind, and poikilothermic — body

in a mammal.[^jarvis1981] They are hairless, effectively blind, and poikilothermic: body

temperature tracks the burrow rather than being defended against it.

temperature follows the burrow instead of being held against it.

The relevant number is the mismatch between size and lifespan. A 35-gram rodent should live a few

What matters is the mismatch between size and lifespan. A 35-gram rodent would be expected to live

years; captive naked mole-rats have exceeded thirty, several times longer than allometry predicts

a few years; captive naked mole-rats have exceeded thirty, several times longer than allometry

for their mass and far beyond any other rodent. That gap is what drew biogerontology to the

predicts for their mass and far beyond any other rodent. That gap drew biogerontology to the

species, and it is the reason the animal appears in nearly every discussion of what sets

species, and it is why the animal appears in nearly every discussion of what sets

[[maximum-human-lifespan|species-specific lifespan]].

[[maximum-human-lifespan|species-specific lifespan]].

```timeline

```timeline

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academic laboratories and later at [[calico]], which recruited her and the animals in the 2010s.

academic laboratories and later at [[calico]], which recruited her and the animals in the 2010s.

The other major line runs through Vera Gorbunova and Andrei Seluanov's laboratory at Rochester,

The other major line runs through Vera Gorbunova and Andrei Seluanov's laboratory at Rochester,

which supplied the cell-biology side. Nearly all published naked mole-rat demography traces back

which supplied the cell-biology side. Nearly all published naked mole-rat demography traces back

to a small number of captive colonies, which is both why the records are so complete and why they

to a small number of captive colonies. That concentration explains why the records are so

are contested.

complete, and also why they are contested.

## The mortality curve

## The mortality curve

In almost every mammal studied, the chance of dying in the next interval rises roughly

In almost every mammal studied, the chance of dying in the next interval rises roughly exponentially

exponentially with age after maturity — the Gompertz pattern, which in humans amounts to a doubling

with age after maturity. This is the Gompertz pattern, which in humans amounts to a doubling every

every seven or eight years. Ruby, Smith and Buffenstein compiled 3,329 naked mole-rat records with

seven or eight years. Ruby, Smith and Buffenstein compiled 3,329 naked mole-rat records with

resolved birth and death dates and found no such rise: the daily hazard stayed below one in ten

resolved birth and death dates and found no such rise: the daily hazard stayed below one in ten

thousand across the whole observed range, with no detectable increase after sexual maturity at

thousand across the whole observed range, with no detectable increase after sexual maturity at about

about six months.[^ruby2018]

six months.[^ruby2018]

> [!key] What the claim is

> [!key] What the claim is

> The result is about the *shape* of the mortality curve, not about immortality. Naked mole-rats

> The result concerns the *shape* of the mortality curve and says nothing about immortality. Naked

> die — of infection, of injury, occasionally of cancer. What is absent is the acceleration, which

> mole-rats die of infection, of injury, and occasionally of cancer. What is absent is the

> is the demographic signature aging normally leaves.

> acceleration in death rates, the demographic signature aging normally leaves.

The analysis drew a formal published comment. Dammann and colleagues argued in 2019 that the

The analysis drew a formal published comment. Dammann and colleagues argued in 2019 that the

dataset is skewed toward recent births: about 87% of the animals were observed for eight years or

dataset is skewed toward recent births: about 87% of the animals were observed for eight years or

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eighteen years.[^dammann2019] They also noted a long stretch of the colony history with no recorded

eighteen years.[^dammann2019] They also noted a long stretch of the colony history with no recorded

deaths, which would depress hazard estimates, and showed with data from a related genus that

deaths, which would depress hazard estimates, and showed with data from a related genus that

simulated record loss inflates median survival substantially. The original authors had already

simulated record loss inflates median survival substantially. The original authors had already

conceded that they could not rule out an as-yet-undetectable Gompertzian component. The honest

conceded that they could not rule out an as-yet-undetectable Gompertzian component. On the current

summary is that the curve is flat over the range that has been well observed, and that range does

evidence the curve is flat over the range that has been well observed, and that range does not yet

not yet cover old age as the species defines it.

cover old age as the species defines it.

## Cancer resistance

## Cancer resistance

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experimental transformation.[^tian2013] The responsible enzyme, hyaluronan synthase 2, differs from

experimental transformation.[^tian2013] The responsible enzyme, hyaluronan synthase 2, differs from

its mouse counterpart, and the animals also degrade the polymer more slowly.

its mouse counterpart, and the animals also degrade the polymer more slowly.

The absolute version of the claim did not survive. Delaney and colleagues reported two tumours in

The absolute version of the claim has not held up. Delaney and colleagues reported two tumours in

zoo-housed naked mole-rats in 2016, and further neoplasms have since been described in captive

zoo-housed naked mole-rats in 2016, and further neoplasms have since been described in captive

colonies.[^delaney2016] "Cancer-resistant" is defensible; "cancer-proof" is not, and the shift

colonies.[^delaney2016] "Cancer-resistant" is defensible and "cancer-proof" is not. The difference

matters, because a species with zero tumours and a species with rare tumours imply different

matters, because a species with zero tumours and a species with rare tumours imply different

mechanisms.

mechanisms.

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Sealed burrows crowded with animals run low on oxygen. Park and colleagues reported that naked

Sealed burrows crowded with animals run low on oxygen. Park and colleagues reported that naked

mole-rats tolerate hours of severe hypoxia and survive eighteen minutes of total anoxia without

mole-rats tolerate hours of severe hypoxia and survive eighteen minutes of total anoxia without

apparent injury, by switching glycolysis from glucose to fructose — a route that bypasses the

apparent injury by switching glycolysis from glucose to fructose, a route that bypasses the

phosphofructokinase step where glycolysis normally shuts itself down.[^park2017] The animals

phosphofructokinase step where glycolysis normally shuts itself down.[^park2017] The animals

express the fructose transporter GLUT5 broadly and accumulate fructose in the brain under anoxia.

express the fructose transporter GLUT5 broadly and accumulate fructose in the brain under anoxia.

The finding is cited as a possible template for limiting damage in stroke and cardiac arrest, and

The finding is cited as a possible template for limiting damage in stroke and cardiac arrest, and

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[[mitochondrial-dysfunction|mitochondrial]] insults that would be expected to shorten life, and

[[mitochondrial-dysfunction|mitochondrial]] insults that would be expected to shorten life, and

show the same [[cellular-senescence|senescent-cell]] accumulation and

show the same [[cellular-senescence|senescent-cell]] accumulation and

[[telomeres-and-telomerase|telomere]] biology only partly resembling the mouse's. The genome, published

[[telomeres-and-telomerase|telomere]] biology only partly resembling the mouse's. The genome, published

in 2011, was read for candidate adaptations rather than delivering a single one.[^kim2011]

in 2011, yielded a list of candidate adaptations, not a single explanation.[^kim2011]

> [!note] What the species does not settle

> [!note] What the species does not settle

> A flat mortality curve is not the same as an absent aging process. Naked mole-rats do show

> A flat mortality curve is not the same as an absent aging process. Naked mole-rats do show

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## What transfers to humans

## What transfers to humans

Nothing, so far. The one result that crossed a species boundary is Zhang and colleagues' transgenic

So far, nothing has transferred to people. The one result that crossed a species boundary is Zhang

mouse carrying the naked mole-rat hyaluronan synthase gene: tumour incidence in animals over 27

and colleagues' transgenic mouse carrying the naked mole-rat hyaluronan synthase gene: tumour

months fell from 83% to 49%, median lifespan rose about 4% and maximum about 12%, with the

incidence in animals over 27 months fell from 83% to 49%, median lifespan rose about 4% and maximum

transcriptional signature shifting toward reduced inflammation.[^zhang2023] That is a real effect

about 12%, with the transcriptional signature shifting toward reduced inflammation.[^zhang2023] The

and a small one, and it is mouse-to-mouse.

effect is real but small, and it was obtained entirely in mice.

> [!caution] A title worth reading closely

> [!caution] A title worth reading closely

> The preprint of the 2023 study was called "Increased hyaluronan by naked mole-rat HAS2 extends

> The preprint of the 2023 study was called "Increased hyaluronan by naked mole-rat HAS2 extends

> lifespan in mice". The version published in *Nature* is called "improves healthspan in mice".

> lifespan in mice". The version published in *Nature* is called "improves healthspan in mice".

> The lifespan numbers are in both; the framing changed in review, which is a fair signal of how

> The lifespan numbers are in both. The framing changed in review, a fair signal of how much weight

> much weight a 4% median gain in one mouse strain will carry.

> a 4% median gain in one mouse strain will carry.

Moving further would mean a [[gene-therapy-for-aging]] problem: delivering or editing a synthase

Moving further would mean a [[gene-therapy-for-aging]] problem: delivering or editing a synthase

gene in human tissue, with the difficulties that [[somatic-gene-therapy|somatic delivery]] always

gene in human tissue, with the difficulties that [[somatic-gene-therapy|somatic delivery]] always

brings. The alternative is a small molecule that raises high-mass hyaluronan without the risks that

brings. The alternative is a small molecule that raises high-mass hyaluronan without the risks that

come with a matrix polymer implicated in tissue remodelling, and no such compound has been

come with a matrix polymer implicated in tissue remodelling, and no such compound has been

described. Hyaluronic acid is already used in

described. Hyaluronic acid is already used in medicine, in dermal fillers and joint injections, at

medicine, in dermal fillers and joint injections, at molecular masses far below the naked

molecular masses far below the naked mole-rat's and with no claim on aging. The species' broader

mole-rat's and with no claim on aging. The species' broader contribution is evidential rather than

contribution is evidential rather than pharmacological. It is the strongest existing argument that

pharmacological: it is the strongest existing argument that mammalian mortality acceleration is not

mammalian mortality acceleration is not obligatory, the premise on which the

obligatory, which is the premise the [[geroscience-hypothesis]] rests on.

[[geroscience-hypothesis]] rests.

## Limits of the model

## Limits of the model

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the species barely exist. Eusociality confounds it further: breeders and non-breeders differ

the species barely exist. Eusociality confounds it further: breeders and non-breeders differ

physiologically, and a caste system with reproductive suppression has no human analogue, so the

physiologically, and a caste system with reproductive suppression has no human analogue, so the

comparison that matters, between this rodent and other rodents, has a social variable tangled into

comparison that matters, between this rodent and other rodents, has a social variable tangled into

it. And the animal is separated from humans by tens of millions of years of

it. The animal is also separated from humans by tens of millions of years of evolution, so nothing

evolution, which is why nothing here reads as directly as a mouse result does, for better and

here reads across as directly as a mouse result does, for better and worse.

worse.

The deeper limit is the one every comparative programme hits. Long-lived species each solved the

Every comparative programme meets a deeper limit. Long-lived species each solved the problem

problem differently, so there is no shared mechanism to copy, and a trait that evolved inside one

differently, so there is no shared mechanism to copy, and a trait that evolved inside one genome

genome does not necessarily do anything useful inside another. Borrowing a gene from an extreme

does not necessarily do anything useful inside another. Borrowing a gene from an extreme organism

organism is a strategy with a poor record — the same difficulty applies to

has a poor record as a strategy, and the same difficulty applies to

[[tardigrade-genes|tardigrade damage-suppression genes]].

[[tardigrade-genes|tardigrade damage-suppression genes]].

## Outlook

## Outlook

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counterargument is that a decade of it has already produced one modest mouse study, and that

counterargument is that a decade of it has already produced one modest mouse study, and that

interventions with human data behind them, such as [[caloric-restriction|dietary restriction]] and

interventions with human data behind them, such as [[caloric-restriction|dietary restriction]] and

[[exercise-and-aging|exercise]], remain the comparator any naked mole-rat-derived candidate would

[[exercise-and-aging|exercise]], remain the comparator any naked mole-rat-derived candidate would

have to beat, as does [[rapamycin]] in the animal literature. Neither position has been settled by evidence,

have to beat, as does [[rapamycin]] in the animal literature. Evidence has settled neither

and no [[aging-biomarkers|biomarker]] currently in use would detect the difference early enough to

position, and no [[aging-biomarkers|biomarker]] currently in use would detect the difference early

adjudicate it in a human trial.

enough to adjudicate it in a human trial.

## See also

## See also

removed, struck through added, underlinedLine numbers count the serialised markdown of each revision, frontmatter included.

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