Updated June 2026. Originally published May 2019.
Reversing aging in humans by 2030–2035, pets now?
Your comprehensive guide to the 12 hallmarks of aging and the companies racing to defeat death
For hundreds of years, scientists have predicted finding a way to reverse aging within 5–10 years. They still believe that timeline is accurate. (Yes, really. And no, we’re not holding our breath either — but the science is getting interesting enough that maybe you should start doing some planks.)
We sit at an inflection point where we can:
- See how the body works at the molecular level
- Modify our genomes and microbiomes
- Analyze vast amounts of data with powerful computing and machine learning
- Produce synthetic biology at the nanoscale level
- Share and collaborate on science globally
Scientists have figured out how to increase the lifespan of roundworms by 500%. Researchers have also reversed some aspects of aging and disease in dogs and mice. Pet-focused therapies have advantages — owners can treat animals without the same FDA regulatory burden that applies to human medicines. Rejuvenate Bio and Phibro Animal Health are developing a cardio-protective gene therapy to stop mitral valve heart failure in dogs. Animal Biosciences offers a daily longevity supplement for dogs, cats, and horses called LeapYears. Loyal is furthest along: in February 2025, its LOY-002 drug received FDA “Reasonable Expectation of Effectiveness” designation for healthy lifespan extension in dogs — the first time the FDA formally recognized lifespan extension as a valid clinical goal, establishing a potential regulatory pathway for human longevity medicines. Loyal raised $100 million in February 2026 to advance LOY-002 toward FDA approval.
(Of note, although we haven’t yet achieved age-reversal, owning pets can increase longevity. Just choose the right ones — dogs are great, tigers are problematic.)
What’s new since our last update
The field just reached a milestone it has been working toward for decades. On June 9, 2026, Life Biosciences dosed the first human participant in a Phase 1 clinical trial of ER-100, a cellular rejuvenation therapy using partial epigenetic reprogramming. This is the first time a cellular reprogramming drug has ever entered human clinical trials with FDA authorization. The therapy uses three of the four Yamanaka transcription factors (OCT4, SOX2, KLF4) to reset the epigenetic age of retinal cells, targeting open-angle glaucoma (OAG) and non-arteritic anterior ischemic optic neuropathy (NAION). Life Biosciences received FDA investigational new drug (IND) clearance on January 15, 2026. We cover this under Hallmark #7 below.
Unity Biotechnology shut down. The most prominent public senolytic company — which raised nearly $300 million before its 2018 IPO — dissolved in September 2025 after failing to meet primary endpoints in its diabetic macular edema trial. Its shares went worthless. Unity’s closure doesn’t invalidate the biology of senolytics; it demonstrates how hard clinical translation is, even when the foundational science is compelling.
GLP-1 drugs are emerging as longevity interventions. Semaglutide (Ozempic, Wegovy) and related GLP-1 receptor agonists — originally developed for diabetes and obesity — now show effects across multiple hallmarks of aging simultaneously: reducing chronic inflammation, improving cardiovascular outcomes, showing neuroprotective signals, and reversing fatty liver disease. For more on the brain-related implications, see Outthink Your Brain.
ARPA-H launched PROSPR. In December 2024, the Advanced Research Projects Agency for Health launched the PROSPR (PROactive Solutions for Prolonging Resilience) program with an explicit goal: extend American healthspan by 20 years. The program awarded $144 million to aging intervention projects in early 2025, including mTORC1-targeting work by Cambrian Bio — a meaningful signal that the US government now treats aging biology as a national health priority.
Measuring your biological age
To determine whether aging can be reversed, you first need to know where you’re starting from. Biological age testing compares your physiological state to your chronological age — a fifty-year-old may have the relative health of someone meaningfully younger or older. Many companies now offer biological age tests, though all have limitations. Keep Health’s guide to measuring your biological health covers what these tests actually tell you and what they don’t.
Some scientists believe there are simpler, cheaper, and more accurate proxies: asking “How old do people think you look?” and checking “How fast do you walk?” Both show surprisingly strong correlations with actual biological age. (So if strangers keep offering you their seat on the bus, maybe it’s time to pick up the pace.)
The 12 + 1 hallmarks of aging
Once you know your biological age, these twelve biological hallmarks explain what to address. Scientists originally identified nine hallmarks in a landmark 2013 Cell paper by López-Otín and colleagues. A 2023 update in Cell expanded the list to twelve, adding disabled macroautophagy, dysbiosis, and splitting chronic inflammation into its own category. We add one more that the scientific community has clearly missed.
Think of these twelve hallmarks as the Avengers of Aging — except instead of fighting Thanos, they quietly destroy your body from the inside. The good news: multiple companies compete to bring you solutions for each one. We present them in alphabetical order, along with the brave souls trying to fix them.
#1: Altered intercellular communication
When your cells forget how to talk to each other (like a bad group chat)
As cells age, they fail to communicate properly. This breakdown affects tissue function and contributes to age-related decline. Cell-to-cell signaling pathways become disrupted, coordination problems spread throughout the body, and eventually the whole system starts to resemble a group project where nobody’s reading the messages.
The players: Research is ongoing, but no major companies have specifically targeted this hallmark yet. Most work continues in academic labs trying to understand which signals get scrambled first and why.
#2: Cellular senescence
When zombie cells refuse to die and ruin everything for everyone
Although the body naturally removes old cells as we age, some survive and cause dysfunction. These “senescent cells” are like that coworker who should have retired years ago but just won’t leave — except instead of boring you with old stories, they’re actively poisoning your tissues with pro-inflammatory molecules.
Eating colorful fruits and vegetables helps: Fisetin slows aging by aiding in removing senescent cells, though diet alone isn’t sufficient. An important balance point: cells need to become senescent as a barrier to cancer. People with low senescence carry a high risk of neoplasms. (Balance, as always, is key.)
UPDATE — Unity Biotechnology closed September 2025. The company that pioneered senolytics and raised nearly $300 million before its 2018 IPO dissolved in September 2025. Its final trial — testing the senolytic UBX1325 in diabetic macular edema — failed to meet its primary endpoint. While disappointing, the underlying senolytic hypothesis remains scientifically valid; the challenge is clinical translation, not the biology. Unity’s closure cleared the public senolytics field, leaving private companies to carry forward.
The senolytic warriors:
- Partnered with Astellas Pharma in March 2025 to develop next-generation senolytics targeting fibrotic diseases
- Also developing ER-100, its epigenetic restoration therapy — now in Phase 1 human trials (see Hallmark #7)
- Well-funded and scientifically ambitious
- Launched a clinical trial in January 2025 with 108 participants testing Fisetin, Urolithin A, and Ergothioneine
- Evaluating combined effects on skin health and organ rejuvenation taken orally
[Mayo Clinic / Dr. James Kirkland](https://www.mayoclinic.org/)
- The foundational researcher in senolytic science, Dr. Kirkland has been at this longer than most
- Tested dasatinib combined with quercetin and fisetin in multiple senolytic drug clinical trials. Results were mixed
- A February 2025 pilot study showed intermittent dasatinib/quercetin (DQ) treatment may improve cognition in older adults at risk for Alzheimer’s
- Formed the Translational Geroscience Network to coordinate anti-aging work across 8 research institutions
- Using its ALEMBIC™ AI platform to discover novel senolytic agents
- Targeting age-related skin conditions like dermatitis and psoriasis via small molecule senolytics
- $40 million raised in a Series A round in April 2024
Oisín Biotechnologies (Seattle, founded 2016)
- Technology can selectively kill any cell class with high p16 expression (a senescence marker)
- Also targeting visceral fat removal and muscle addition via follistatin therapy
- Challenge: “Not every cell that expresses high p16 is senescent; and not every senescent cell has high p16”
Senisca (UK-based)
- Based on University of Exeter research by Dr. Lorna Harries
- Found that stopping ERK and AKT pathways reduces senescent cells
- Raised $2 million in 2022 and $4 million in March 2024; still preclinical but progressing
#3: Chronic inflammation
Your immune system’s version of never letting go of grudges
Chronic, harmful inflammation can have many causes: virus or bacteria, autoimmune disorders, sugary and fatty foods, or how you handle stress. As cells age and fail to communicate properly, low-grade chronic inflammation (scientists call it “inflammaging” — they do have a sense of humor) increases throughout the body, contributing to tissue damage and age-related diseases. This persistent inflammatory state links to cardiovascular disease, Alzheimer’s, diabetes, and basically every disease you’d rather not get.
New development: GLP-1 receptor agonists like semaglutide have demonstrated meaningful anti-inflammatory effects in large-scale cardiovascular trials, reducing systemic inflammation markers alongside their metabolic benefits. Researchers now view GLP-1 drugs as potential multi-hallmark interventions, not just metabolic medicines.
The anti-inflammatory brigade: Researchers are attempting to prevent immune system decline and dysfunction. See Keep Health’s Immunity Against Aging for the latest. Multiple pharmaceutical companies are working on anti-inflammatory drugs, but most still target specific diseases rather than aging itself.
#4: Disabled macroautophagy
When your cellular recycling program goes on permanent strike
Macroautophagy is the cell’s recycling and cleaning system. When working properly, cells break down and recycle damaged components, proteins, and organelles. As we age, this autophagy process becomes less efficient, letting damaged mitochondria, misfolded proteins, and cellular debris pile up. Think of it as forgetting to take out the trash for 30 years.
The autophagy activators:
- Research from 2024 confirmed spermidine is essential for fasting-mediated autophagy and longevity
- Acute nutrient deprivation immediately increases spermidine biosynthesis in yeast, flies, mice, and humans
- External supplementation may compensate as endogenous spermidine levels decline with aging
- Sam Altman’s personal $180 million investment funds this multi-approach longevity company
- Phase 1 human trials started for RTR242, a pill designed to boost autophagy for Alzheimer’s disease prevention
- In August 2025, Retro announced that its OpenAI partnership made cellular reprogramming 50 times more efficient
- Working on enhancement of chaperone-mediated autophagy (a specific type of autophagy)
- Also developing epigenetic restoration therapies — including ER-100, now in Phase 1 human trials
#5: DNA damage / genomic instability
When your genetic instruction manual gets coffee stains and torn pages
Free radicals, reactive oxygen species, and reactive nitrogen species accumulate as we age. When mitochondria become inefficient and dysfunctional, they produce an altered form of oxygen that damages DNA and proteins. A balance between free radicals and antioxidants is necessary for proper physiological function; when free radicals overwhelm the body’s ability to regulate them, oxidative stress ensues.
The DNA defenders:
NAD+ boosters — The leading potential solution for DNA protection and repair is NAD+. See our article on Nicotinamide Riboside for the full picture on NAD+ precursors.
SIRT6 research — Vera Gorbunova’s lab found that the gene sirtuin 6 (SIRT6) drives more efficient DNA repair in longer-lived species. Enhancing SIRT6 activity in humans is an active research target. (If we could just borrow some genes from naked mole rats, we’d be set.)
Matter Bio — Focused specifically on increasing genomic stability to unlock healthy longevity, targeting the reversal of age-accumulated somatic DNA mutations. Still early-stage but addressing a fundamental aging mechanism.
#6: Dysbiosis
When your gut microbiome becomes a hostile real estate market
Your gut microbiome — the trillions of bacteria, fungi, and other microorganisms living in your digestive system — plays a crucial role in aging. As we age, diversity and balance of beneficial gut bacteria decline while harmful bacteria increase. This imbalance contributes to inflammation, immune dysfunction, and metabolic problems. The gut-brain axis means that microbiome health affects not just digestion but also brain function, mood, and overall health. Your gut bacteria are basically running a shadow government, and with age, that government becomes increasingly corrupt.
The microbiome managers:
Probiotics and prebiotics — Multiple companies are developing age-specific probiotic formulations, though the science is still catching up to the marketing. Key targets include maintaining beneficial species like Akkermansia muciniphila and various Lactobacillus strains.
Fecal Microbiota Transplantation (FMT) — Yes, it’s exactly what it sounds like. Research shows it can improve healthspan in mice, and human trials are ongoing for various age-related conditions. You cannot source this from your neighbor.
Microbiome sequencing companies — Companies like Viome offer microbiome testing to identify dysbiosis, though converting those results into actionable interventions remains somewhat unclear.
#7: Epigenetic alterations
When your genes start reading the wrong instruction manual
Environmental factors — diet, temperature, oxygen levels, light cycles, and mutagens — change how genes are expressed. These alterations accumulate over a lifetime. Multiple concurrent mutations in cell division genes cause cancers. Research has also found that wrinkly cell membranes press on genes and accidentally activate parts that should stay dormant in certain cell types. (Your nucleus is basically a crumpled paper bag pressing random genetic buttons.)
UPDATE — June 9, 2026: The first human receives a cellular reprogramming drug. Life Biosciences dosed the first participant in its Phase 1 trial of ER-100 on June 9, 2026 — the most significant development in this field since the Yamanaka factors were discovered. ER-100 uses three of the four Yamanaka transcription factors (OCT4, SOX2, KLF4, or OSK) to reset the epigenetic age of retinal cells, targeting open-angle glaucoma and NAION. FDA IND clearance arrived on January 15, 2026. The trial evaluates safety, tolerability, and visual function endpoints, with 5-year follow-up. Life Biosciences, co-founded by Harvard’s David Sinclair, argues that using only three of the four Yamanaka factors — and controlling expression through doxycycline — meaningfully reduces the tumor risk that has plagued earlier reprogramming research.
The epigenetic reprogrammers:
- First company to enter human clinical trials with a cellular epigenetic reprogramming therapy (June 9, 2026)
- ER-100 Phase 1 trial targets optic neuropathies using OSK transcription factor expression
- Co-founded by David Sinclair (Harvard Medical School), whose work on epigenetic aging clocks frames the company’s entire approach
- The best-funded private longevity company in the world, having raised $5.56 billion with Jeff Bezos among backers
- Appointed Dr. Joan Mannick as Chief Medical Officer in mid-2025 — a clear signal of approaching clinical development
- Published landmark 2024 Science Translational Medicine mouse study showing partial reprogramming extended lifespan and improved health markers
- Human safety testing in ex vivo organs reportedly began in August 2025
- Not yet in human clinical trials for in vivo applications, but positioning for that move
- Co-founded by Coinbase CEO Brian Armstrong; raised $130 million in 2025 (largest longevity round of the year) and a further $435 million in a Series C in 2026
- Screened over 3,000 transcription factor combinations; identified more than 20 capable of restoring youthful function in hepatocytes and T cells
- By December 2025, reported being “close” to clinic-ready epigenetic reprogramming therapies
- Eli Lilly participated in its 2026 Series C — meaningful validation from big pharma
- Raised $16 million seed in October 2024
- Uses machine learning to find safer and more efficient genes for reprogramming
- More targeted approach than Altos, focused specifically on the epigenetic clock developed by Steve Horvath
- Working on cellular reprogramming alongside autophagy and plasma therapeutics
- In August 2025, announced its OpenAI partnership made reprogramming 50 times more efficient
- Already in human trials with RTR242 for autophagy; reprogramming human trials to follow
#8: Loss of proteostasis
When your proteins lose their shape and their minds
Proteostasis — the stability and proper folding of proteins throughout the cell — breaks down with biological age. Proteins need correct folding, correct location, correct concentration, and timely degradation when done. When proteostasis fails, misfolded proteins accumulate and cause diseases like Alzheimer’s, Parkinson’s, and other neurodegenerative conditions.
See Keep Health’s Keep Your Proteins in Shape article for the companies working on this hallmark. NAD+ precursors, particularly nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), support the mitochondrial function underpinning proteostatic maintenance.
#9: Mitochondrial dysfunction
When your cellular power plants start blacking out
Mitochondria are the energy-producing organelles in each cell. As we age, mitochondrial function declines — they become less efficient, produce more reactive oxygen species, and trigger systemic inflammation. Nicotinamide riboside (NR) produces NAD+, the communication molecule between the cell nucleus and mitochondria. When NAD+ levels drop, mitochondrial communication falters and dysfunction follows.
The mitochondria mechanics:
NAD+ supplements — NR and NMN are the leading consumer-accessible interventions, though the research on whether oral supplementation meaningfully raises intracellular NAD+ in humans is still developing.
Mitrix Bio — Growing mitochondria for transplantation to bolster energy production and regenerate aged or dysfunctional tissues. One challenge: 10% of your body weight is mitochondria, and your immune system mounts a response when it detects free-floating mitochondria in your bloodstream.
Hydrogen sulfide rejuvenation — Small quantities of hydrogen sulfide can rejuvenate mitochondria in animal models. Still primarily a research-stage approach.
#10: Deregulated nutrient sensing
When your body stops knowing how hungry it is
Nutrient sensing pathways — including mTOR, AMPK, sirtuins, and insulin/IGF-1 signaling — regulate how cells respond to food availability. When these pathways become dysregulated with age, cells fail to adapt properly to nutrient conditions, contributing to metabolic disease, impaired cellular maintenance, and accelerated aging.
Intermittent fasting and caloric restriction activate AMPK and sirtuins while suppressing mTOR, mimicking some of the nutrient-sensing corrections that extend lifespan in model organisms. Rapamycin, an mTOR inhibitor, is the most studied pharmacological intervention for this hallmark, with ongoing human trials. Berberine also activates AMPK through a mechanism similar to metformin.
Cambrian Bio received an ARPA-H PROSPR grant in early 2025 to develop mTORC1-targeting interventions for healthspan extension — the clearest signal yet that mTOR modulation is moving toward human clinical validation with federal backing.
#11: Stem cell exhaustion
When your body’s repair crew goes on strike permanently
Five types of stem cells replenish tissues throughout the body: hematopoietic stem cells (blood), mesenchymal stem cells, neural stem cells, epithelial stem cells, and others. As we age, these stem cells accumulate damage and lose their ability to divide and differentiate. Tissue maintenance fails, regeneration slows, and the body’s capacity to recover from injury and disease declines.
To keep blood stem cells healthy until bone marrow rejuvenation techniques become widely available, the Cleveland Clinic recommends a diet rich in protein — lean meats, fish, beans, nuts, milk, eggs — combined with healthy levels of iron and vitamins B9 and B12. See Bloody Good Health for more on bone marrow aging.
Cellular reprogramming approaches — including those pursued by Life Biosciences, Altos Labs, and Retro Biosciences — may ultimately address stem cell exhaustion by restoring cellular youth at the epigenetic level, though this remains a longer-term goal than their current disease-specific clinical programs.
#12: Telomere shortening / attrition
When your chromosomes start unraveling at the ends
Telomeres are the protective caps at the ends of each DNA strand. They gradually shorten as cells divide, eventually reaching a length at which DNA dysfunction occurs. Critically short telomeres drive cellular senescence, mitochondrial dysfunction, and chronic inflammation — connecting this hallmark to several others above.
Elizabeth Blackburn’s Nobel Prize-winning work on telomeres and telomerase remains the foundational science. To understand how lifestyle and psychological habits protect telomeres in practice, The Telomere Effect — co-authored by Blackburn — is an accessible, research-based guide.
Life Length offers telomere measurement as part of biological age profiling. Keep Health’s Biological Age Tests article covers what telomere length testing can and can’t tell you.
#13: The Keep Health bonus hallmark — failure to exercise
The one the scientists left out
We add one hallmark the 2023 Cell paper conspicuously omitted: not exercising. No intervention in the longevity toolkit has a stronger, more consistent, more replicated evidence base than regular physical activity. Exercise improves mitochondrial function, reduces chronic inflammation, supports telomere maintenance, enhances insulin sensitivity, activates autophagy, and reduces senescent cell burden — hitting at least six of the twelve official hallmarks simultaneously.
Keep Health’s articles on strength training, walking, VO2 max, flexibility, and proper breathing cover the most impactful ways to apply this across your life.
The bottom line on reversing aging in 2026
The field reached a genuine milestone on June 9, 2026, when the first human received a cellular reprogramming therapy with FDA authorization. Life Biosciences’ ER-100 trial is Phase 1 — safety and tolerability are the primary endpoints, not efficacy — and many such early trials fail. But the transition from animal models to human patients is real, and the scientific community has been working toward exactly this moment since Yamanaka won the Nobel Prize in 2012.
Unity Biotechnology’s closure, meanwhile, is a useful reminder that the gap between compelling aging biology and successful clinical translation remains wide. Senescent cells do drive aging. Clearing them helps in animal models. Translating that into a drug that works in specific human tissues, with acceptable safety and clear endpoints, is a different and harder problem.
The most realistic near-term path to human longevity medicines runs through disease-specific applications — glaucoma, Alzheimer’s, kidney disease, cardiovascular disease — rather than through programs that explicitly target “aging” as such. That’s partly because the FDA doesn’t yet classify aging as a disease, though Loyal’s LOY-002 milestone in dogs may eventually create a regulatory path that changes this.
For further reading on the scientific and investment landscape, see Keep Health’s related articles on Cellular Reprogramming, Preventing Age-Related Diseases, Investment Opportunities, and Anti-Aging Companies.
As your reward for reading this far, watch Nobel laureate Shinya Yamanaka’s original TED Talk on the discovery of induced pluripotent stem cells — the foundational work behind every cellular reprogramming therapy described above. Then do some planks.
