The plan to end aging

Plan A · Repair

The plan to end aging.

How to address aging as a root cause:

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Pencil sketch of one woman walking toward the viewer at five ages, younger each time, with blue line-art of cells, a heart and a liver flowing between them

01 Why aging is the target

In Humans, aging increases your risk of death.

Mortality

Chance of Death By Age

90year old1 in 6chance of death this year
0%4%7%11%14%18% 0102030405060708090 Age (years) Chance of death per year

Chance of death per year. Source: @statto, as shown in the deck. Hover a point or pick an age.

But in some species, aging doesn't mean a greater chance of disease or death.

We can get older healthfully.

Negligible senescence

Human vs. mole rat.

0%1%2%3%4%5% Age (years) Chance of death per year Humans Mole rats

The naked mole rat’s chance of dying barely changes with age. Ours climbs after 65. Negligible senescence, as charted in the deck.

Source and limits: the comparison is the deck’s chart of negligible senescence in the naked mole rat. It shows that a flat mortality curve exists in another mammal. It does not show that humans can be rejuvenated, or by what mechanism.

02 The race to 160

Lifespan is Malleable

We have already doubled human lifespan twice thanks to sanitation, public health, and biomedicine.

We believe it is possible to double it again. To allow humans to live to 160+.

But it requires a new approach: repair.

~20 Hunter-gatherer ~40 Industrial ~80 Modern 160+ The 3Rs ×2 ×2 Repair 122 record
~20 → ~40 → ~80 → 160+

Two doublings mostly prevented early death. The third requires repair.

The 20 → 40 → 80 figures are life expectancy at birth, not maximum lifespan. The longest verified human life is 122. 160+ is the goal the plan sets, not a result.

03 Plan A

Reprogram. Regenerate. Replace.

the three levers that can dramatically move the needle on human lifespan

Reprogram Reset cell state Regenerate Rebuild in place Replace Swap the component Reset what is salvageableRegenerate what is missingReplace what is irreparable One maintenance system
Reprogram · Regenerate · Replace

Three levers. One maintenance system.

See the slide
Deck illustration: a human figure in the center with three circled levers around it. Reprogram, an old cell becoming a young cell. Replace, a worn heart swapped for a new one. Regenerate, scar tissue rebuilt into healthy tissue.
From the deck. Reset what is salvageable · Regenerate what is missing · Replace what is irreparable.

04 Lever one · Reprogram

Yamanaka factors reset cell identity.

Four transcription factors reopen the pluripotency program.

Deck slide: Yamanaka factors resetting cell identity. 1 adult somatic cell. 2 deliver OSKM: OCT4, SOX2, KLF4, c-MYC. 3 epigenetic reset: somatic program off, pluripotency network on. 4 iPSC: self-renewal and many cell fates. Stop early for partial reprogramming; continue to completion for iPSC. Full reprogramming erases the original cell identity.
From the deck. Stop early → partial reprogramming. Continue to completion → iPSC.
  1. 1 Adult somatic cell A differentiated cell with its identity set.
  2. 2 Deliver OSKM OCT4SOX2KLF4c-MYC
  3. 3 Epigenetic reset Somatic program off. Pluripotency network on.
  4. 4 iPSC Self-renewal + many cell fates
Deck slide: an aged neuron receives a brief OSK pulse of OCT4, SOX2 and KLF4 and becomes the same cell in a younger state. A dashed branch marked stop before pluripotency leads away from a blank pluripotent cell.

Partial vs. full reprogramming

The same four factors. Two very different stopping points.

  • Partial reprogrammingA brief OSK pulse (OCT4 · SOX2 · KLF4), stopped before pluripotency. Same cell, younger state.
  • Full reprogrammingContinue to completion and the cell becomes an iPSC: self-renewal and many cell fates. Full reprogramming erases the original cell identity.

Status: the deck presents the mechanism and the partial-versus-full distinction. It does not state a development stage for partial reprogramming in people, so none is claimed here.

05 Lever two · Regenerate

Biology already knows how to rebuild.

Shared genes. Different control.

Deck slide: hydra with whole-body renewal, planarian with body regeneration, axolotl with limb regeneration, zebrafish with heart repair, and a human outline sharing the same DNA strand. Shared genes, different control.
  • HydraWhole-body renewal
  • PlanarianBody regeneration
  • AxolotlLimb regeneration
  • ZebrafishHeart repair

The human program is still there

Capacity exists, but it is uneven and declines with age.

  • Development builds
  • Skin renews
  • Bone repairs
  • Liver restores mass
  • Heart scars
Deck slide: development builds organs, skin renews, bone repairs, liver restores mass, heart scars. Capacity exists but it is uneven and declines with age.
Deck slide: the same injury can end two ways. Tissue damage leads either to fibrosis, through inflammation and collagen to lost function, or to regeneration, through resolution and patterning to restored function. The therapeutic target is the decision process.

The same injury can end two ways

Tissue damage, then a decision.

Fibrosis

  1. Inflammation
  2. Collagen
  3. Lost function

Regeneration

  1. Resolution
  2. Patterning
  3. Restored function
The therapeutic target

The therapeutic target is the decision process.

Deck slide in three panels. 1 Nature’s proof: axolotl forelimb regeneration from stump to early blastema to patterning and outgrowth to patterned limb; zebrafish heart regeneration from injury to cardiac progenitors activating to tissue restored. 2 Humans retain parts: liver, skin, bone, muscle, fingertip. 3 Therapeutic hypothesis: immune and fibrosis control, progenitor activation, positional and bioelectric cues, nerves and matrix support, turning scar tissue into an organized blastema-like repair zone. Local, transient, self-limiting.

1 Nature’s proof

Many species naturally regenerate complex tissues.

Axolotl forelimbStump → Early blastema → Patterning & outgrowth → Patterned limb

Zebrafish heartInjury → Cardiac progenitors activate → Tissue restored

Observed in other species

2 Humans retain parts

We can naturally repair and renew many tissues.

  • Liver
  • Skin
  • Bone
  • Muscle
  • Fingertip

Observed in humans

3 Therapeutic hypothesis

We can mobilize regeneration where it is currently limited.

  • Immune + fibrosis control
  • Progenitor activation
  • Positional / bioelectric cues
  • Nerves + matrix support

Scar→Regeneration

Local · Transient · Self-limiting

Hypothesis, not a demonstrated therapy

06 Lever three · Replace

Grow a young part. Swap it in.

When repair is insufficient, replace the failing biological component. From cell engineering to functional replacement.

Deck slide: an aged figure with a damaged liver; patient skin cells become iPSCs, then cells, tissue and a new liver, transplanted into a restored figure. Aged or damaged tissue, patient cells to iPSCs, cells tissues organs, transplant to restored function.
  1. 1Aged / damaged tissue
  2. 2Patient cells → iPSCs
  3. 3Cells · tissues · organs
  4. 4Transplant → restored function

Replacement · Xenotransplantation Early clinical use

Pig organs engineered for human recipients.

69 edits in the eGenesis kidney platform.

  1. 0 Pig antigen genes disabled Reduce antibody recognition.
  2. 0 Human genes added Improve immune and blood compatibility.
  3. 0 Viral copies inactivated Reduce risk from endogenous pig retroviruses.
Early clinical use

Human kidney transplants have begun.

Immunosuppression and long-term safety monitoring remain necessary.

Deck illustration: a pig beside an engineered kidney being placed into a human outline
Deck illustration: human stem cells injected into an animal blastocyst, and a pig with a glowing human pancreas growing inside it

Replacement · Stanford / Nakauchi lab Preclinical

Human tissue grown inside an animal host.

Blastocyst complementation, in three moves.

  1. 1Create an empty organ nicheDisable the host’s ability to make a specific organ or cell type.
  2. 2Add human stem cellsDonor cells could fill the vacancy as the host develops.
  3. 3Recover replacement tissueGoal: patient-matched tissue grown within an animal.
Preclinical

Proof in rodents. Human organs remain a goal.

2026 advance: protecting donor cells from early immune clearance.

Replacement · Renewal Bio Preclinical R&D

Development as a bioreactor.

Patient iPSCs → controlled self-organization → embryo model → organ progenitors (blood, liver, pancreas, neural tissue) → future replacement therapies. Preclinical R&D. Not a reproductive program. Scientific foundation: Prof. Jacob Hanna, Weizmann Institute.

Deck slide: Renewal Bio, development as a bioreactor. Patient iPSCs, controlled self-organization in a vessel, an embryo model, dishes of organ progenitors for blood, liver, pancreas and neural tissue, and a human outline for future replacement therapies. Preclinical R&D, not a reproductive program.
  1. 01Patient iPSCs
  2. 02Controlled self-organization
  3. 03Embryo model
  4. 04Organ progenitorsBloodLiverPancreasNeural tissue
  5. 05Future replacement therapies
Each development stage unlocks new clinical cell types. The shaded band is where the program stood in the 2024 deck. Source: Renewal Bio, 2024.

In the record

  • CellCeci n’est pas un embryon de sourisVol. 185 No. 18 · September 1, 2022
  • NatureEmbryo models: stem cells form structures that mimic two-week-old human embryos19 October 2023
  • CNNA synthetic embryo, made without sperm or egg, could lead to infertility treatments
  • NBC NewsScientists use stem cells to create synthetic mouse embryos
  • CNN HealthScientists report creation of first human synthetic model embryosJune 15, 2023
  • The New York TimesScientists Debut Lab Models of Human Embryos
  • ABC Science‘Synthetic human embryos’ were created using stem cells. What are they, and why were they made?June 20, 2023

Covers and headlines as shown in the deck. The embryo-model work is from the Hanna lab; the stembroid data in the deck is marked confidential and is not reproduced here.

07 Why now

The breakthrough is convergence.

Every technology takes us a step closer. But we need to remain focused on the larger goals.

Single-cell measurement AI biology Gene delivery Cell engineering Developmental biology Immune control Reprogram Replace Regenerate
Six inputs · three outputs

No single technology is enough.

Hover an input or an output.

08 NFX Bio

Who’s building it.

Keep going

Longevity is a society-scale problem.

Living longer and healthier lives will have dramatic impacts on the economy beyond just biotech.

Read the results →
Omri Amirav-Drory

The talk

Omri Amirav-Drory, PhD

General Partner at NFX, where he leads NFX Bio. This site follows his talk. Where we added a sentence of our own, it’s plain-language framing, not new science.

Omri on nfx.com ↗