Genetic codes, biological age scores, wearable device logs, disease risk maps—these are the fuel powering the longevity revolution. But with great data comes great responsibility. In an industry that is both highly personal and deeply technical, data security is no longer optional—it is mission-critical.

The Golden Currency: Why Longevity Research Relies on Sensitive Data

Unlike other scientific fields, life extension depends on multi-layered personal data collected over time:
• Genetic sequences
• Epigenetic age tests
• Health records (EHRs)
• Wearable sensor data
• Cognitive and behavioral assessments

This data is:
• Highly identifiable
• Extremely valuable to hackers
• Legally protected under laws like HIPAA (USA) and GDPR (EU)

For researchers and biotech firms, protecting this data is not just good practice—it’s a legal, ethical, and brand-defining requirement.

The Business Risk: A Breach Could Kill Public Trust

Life extension companies are often startups, balancing innovation with limited resources. But even one data breach can:
• Destroy trust among participants and donors
• Lead to multi-million dollar fines under GDPR or HIPAA
• Invite negative media attention and lawsuits
• Result in loss of access to hospital data and research partnerships

This is why security must be embedded into the very architecture of research platforms—not added as an afterthought.

Regulatory Compliance: A Global Maze

• In the United States, HIPAA governs patient data. Noncompliance can mean up to $1.5 million per violation.
• In the European Union, GDPR treats health and genetic data as “special category” information with strict consent rules.
• Countries like Singapore, Canada, and Australia are building hybrid models that balance research with privacy.

A life extension company working globally must comply with multiple data regimes—often with overlapping or conflicting requirements.

Ethical Frontiers: Consent, Control, and Transparency

Longevity research poses unique ethical questions:
• Do participants know how their data will be used 10 years from now?
• Can they withdraw from a genetic study that has already generated AI predictions?
• How are researchers informing users about secondary data usage?

The concept of “informed consent” must evolve in the age of continuous data streaming and lifelong trials.

This article uncovers the hidden foundation of life extension research: where the data comes from. Understanding these sources is crucial, not only for researchers and clinicians—but for policymakers, funders, and the public who will live longer because of what this data reveals.

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Clinical Frontlines: Hospitals and Medical Facilities

Hospitals remain the most regulated, accurate, and biologically rich environments for collecting longevity data.
• Electronic health records (EHRs) offer real-time data on glucose levels, heart rhythms, and medication outcomes
• Clinical trials in oncology, geriatrics, and cardiology often generate side data relevant to aging mechanisms
• Biosample banks (blood, tissue, saliva) collected under strict protocols fuel aging biomarkers and AI modeling

However, access is tightly controlled by data protection laws (e.g., HIPAA, GDPR), requiring research teams to negotiate permissions and ethics board approvals.

Hospitals are gold mines—but only if you have the map and the key.

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The Digital Age: Online Databases and Direct-to-Consumer Platforms

We are living through a data revolution—with individuals increasingly uploading their health histories voluntarily. This has created a second major source of aging data:
• Online patient registries like PatientsLikeMe allow users to contribute chronic health data for open research
• DNA ancestry platforms like 23andMe offer optional research sharing pipelines (e.g., for Parkinson’s risk, telomere length)
• Health tracking apps like Whoop, Fitbit, and Oura Ring generate millions of datapoints per user per day

These platforms democratize data, but raise important concerns around accuracy, bias, and data ownership.

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Long-Term Observation: Aging Care Facilities and Retirement Homes

A third vital source comes from care environments for the elderly, where biological aging plays out daily and visibly.
• Functional aging metrics like grip strength, walking speed, cognitive tests, and frailty indexes are commonly recorded
• Longitudinal care records allow for real-world evidence on what interventions correlate with healthspan improvement or decline
• Digital transformation in aged care is enabling passive sensor monitoring for sleep, mobility, and safety patterns

This data is rarely standardized and often trapped in private systems—but holds enormous untapped potential for aging science.

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Institutional Archives: Existing Longevity Research Repositories

Many decades of research already exist, locked in public or semi-public databases. These archives are beginning to power meta-studies, AI pattern discovery, and retrospective modeling:
• The UK Biobank holds genetic, lifestyle, and health data from over 500,000 individuals
• The Framingham Heart Study (USA) provides over 70 years of cardiovascular aging data
• The National Institute on Aging (NIA) hosts accessible datasets on dementia, functional aging, and metabolic health

These sources are gold standards—but require careful navigation to extract usable data and align formats.

For centuries, medicine was guided by anecdotes and observations. Today, it is powered by data. In the frontier field of life extension, where biology meets computation, the collection of clean, high-resolution data is not just a necessity—it is a make-or-break foundation.

But data isn’t cheap.

From multi-omics biomarker panels to wearable stress sensors, the tools required to gather biological evidence are expensive, complex, and resource-intensive. This article explores why, in many longevity labs today, data collection can consume over 50% of total research budgets—and why this is not necessarily a bad thing.

The Shift Toward Quantified Biology

Unlike traditional drug discovery, life extension research requires ongoing, longitudinal, and multivariate tracking:
• Epigenetic age clocks must be validated against time-series samples.
• Blood biomarkers for inflammation, lipids, glucose, and cellular debris require cold-chain management and lab testing.
• Metabolomic and transcriptomic data demand cloud-scale storage and AI-assisted analysis.

This means that before any meaningful insights can emerge, vast amounts of high-quality data must be captured and cleaned.

The True Cost of Reliable Longevity Data

• Human sample collection (blood, saliva, etc.) involves clinics, ethics approvals, cold storage, and testing fees.
• Wearable integration (heart rate variability, circadian rhythm tracking) requires device partnerships, onboarding participants, and syncing APIs.
• Subject interviews and video documentation require trained personnel, transcription, and secure data archiving.

Even for a mid-sized longevity study, data collection may cost more than the experimental intervention itself.

In short: the experiment is the tip of the iceberg—data is the entire structure below.

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LongevityDataCosts Summary of data collection vs research costs in this field

EpigeneticClockExplained Explainer card on how DNA methylation clocks are validated

MultiOmicsForAging Interactive look at blood, transcriptome, and microbiome data

AIInBiomarkerTracking Shows AI usage in analyzing time-series biological markers

WearableDataSources Overview of smart devices used in longevity research

DataPrivacyInResearch Highlights ethical handling of participant health data

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A Global Race for Data Sovereignty in Aging

Nations are beginning to recognize that owning aging data may be a geopolitical advantage:
• China’s national longevity genome databases are publicly funded and increasingly commercialized.
• USA-based platforms like Calico (Alphabet) or Altos Labs operate closed data ecosystems but with large AI integration capacity.
• Europe maintains strict GDPR protections, slowing open-data development but preserving individual rights.

This geopolitical angle means that data collection is not just about science—it’s about sovereignty, economics, and power.

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Ethical Considerations in Massive Data Collection

The hunger for data comes with risk:
• Participant identity must be anonymized
• Consent protocols must be continuous, not one-time
• AI interpretation of health signals must be auditable

Funding agencies and research boards are now requiring detailed data ethics plans before approving budgets.

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•   DNA Methylation Age Clocks – Steve Horvath Lab
•   AI + Aging Research (Nature Reviews)
•   Global Alliance for Genomics and Health – Data Ethics
•   WHO – Ethics & Big Data in Health Research

In longevity science, the pursuit of better data is not a burden—it is the breakthrough. Every extra dollar spent on accurate, transparent, and ethical data collection accelerates the discovery of treatments that may one day add healthy decades to human life.

Data is not a side task in life extension.
It is the lifeblood of the entire movement.

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Would you like to move to Article 4 next?

Question 4: “Where do you collect data for life extension research?”
(Hospitals, online databases, aging care facilities, existing archives, etc.)

In a groundbreaking endeavor, scientists at the University of Rochester have successfully transferred a longevity gene from naked mole rats to mice, leading to enhanced health and a longer lifespan for the mice.

Naked mole rats, known for their long lifespans and exceptional resistance to age-related diseases, have long captured the attention of the scientific community. By introducing a specific gene responsible for enhanced cellular repair and protection into mice, the Rochester researchers have opened exciting possibilities for unlocking the secrets of aging and extending human lifespan.

“Our study provides a proof of principle that unique longevity mechanisms that evolved in long-lived mammalian species can be exported to improve the lifespans of other mammals,” says Vera Gorbunova, the Doris Johns Cherry Professor of biology and medicine at Rochester.

Gorbunova, along with Andrei Seluanov, a professor of biology, and their colleagues, report in a study published in Nature that they successfully transferred a gene responsible for making high molecular weight hyaluronic acid (HMW-HA) from a naked mole rat to mice. This led to improved health and an approximate 4.4 percent increase in the median lifespan for the mice.

A unique mechanism for cancer resistance
Naked mole rats are mouse-sized rodents that have exceptional longevity for rodents of their size; they can live up to 41 years, nearly ten times as long as similar-sized rodents. Unlike many other species, naked mole rats do not often contract diseases—including neurodegeneration, cardiovascular disease, arthritis, and cancer—as they age. Gorbunova and Seluanov have devoted decades of research to understanding the unique mechanisms that naked mole rats use to protect themselves against aging and diseases.

University of Rochester researchers successfully transferred a longevity gene from naked mole rats to mice, resulting in improved health and an extension of the mouse’s lifespan. Credit: University of Rochester photo / J. Adam Fenster

The researchers previously discovered that HMW-HA is one mechanism responsible for naked mole rats’ unusual resistance to cancer. Compared to mice and humans, naked mole rats have about ten times more HMW-HA in their bodies. When the researchers removed HMW-HA from naked mole rat cells, the cells were more likely to form tumors.

Gorbunova, Seluanov, and their colleagues wanted to see if the positive effects of HMW-HA could also be reproduced in other animals.

Transferring a gene that produces HMW-HA

The team genetically modified a mouse model to produce the naked mole rat version of the hyaluronan synthase 2 gene, which is the gene responsible for making a protein that produces HMW-HA. While all mammals have the hyaluronan synthase 2 gene, the naked mole rat version seems to be enhanced to drive stronger gene expression.

The researchers found that the mice that had the naked mole rat version of the gene had better protection against both spontaneous tumors and chemically induced skin cancer. The mice also had improved overall health and lived longer compared to regular mice. As the mice with the naked mole rat version of the gene aged, they had less inflammation in different parts of their bodies—inflammation being a hallmark of aging—and maintained a healthier gut.

A fountain of youth for humans?

The findings open new possibilities for exploring how HMW-HA could also be used to improve lifespan and reduce inflammation-related diseases in humans.

“It took us 10 years from the discovery of HMW-HA in the naked mole rat to showing that HMW-HA improves health in mice,” Gorbunova says. “Our next goal is to transfer this benefit to humans.”

They believe they can accomplish this through two routes: either by slowing down the degradation of HMW-HA or by enhancing HMW-HA synthesis.

“We already have identified molecules that slow down hyaluronan degradation and are testing them in pre-clinical trials,” Seluanov says. “We hope that our findings will provide the first, but not the last, example of how longevity adaptations from a long-lived species can be adapted to benefit human longevity and health.”

Reference: “Increased hyaluronan by naked mole-rat Has2 improves healthspan in mice” by Zhihui Zhang, Xiao Tian, J. Yuyang Lu, Kathryn Boit, Julia Ablaeva, Frances Tolibzoda Zakusilo, Stephan Emmrich, Denis Firsanov, Elena Rydkina, Seyed Ali Biashad, Quan Lu, Alexander Tyshkovskiy, Vadim N. Gladyshev, Steve Horvath, Andrei Seluanov and Vera Gorbunova, 23 August 2023, Nature.
DOI: 10.1038/s41586-023-06463-0

The study was funded by the National Institutes of Health.

Published online 2014 Dec 18. doi: 10.4161/auto.36413

PMCID: PMC4502795

PMID: 25484097

Caloric restriction mimetics: natural/physiological pharmacological autophagy inducers

Guillermo Mariño,^1,2 Federico Pietrocola,^1,3 Frank Madeo,^4,* and Guido Kroemer^1,2,5,6,*

Author information Article notes Copyright and License information PMC Disclaimer

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Abstract

Nutrient depletion, which is one of the physiological triggers of autophagy, results in the depletion of intracellular acetyl coenzyme A (AcCoA) coupled to the deacetylation of cellular proteins. We surmise that there are 3 possibilities to mimic these effects, namely (i) the depletion of cytosolic AcCoA by interfering with its biosynthesis, (ii) the inhibition of acetyltransferases, which are enzymes that transfer acetyl groups from AcCoA to other molecules, mostly leucine residues in cellular proteins, or (iii) the stimulation of deacetylases, which catalyze the removal of acetyl groups from leucine residues. There are several examples of rather nontoxic natural compounds that act as AcCoA depleting agents (e.g., hydroxycitrate), acetyltransferase inhibitors (e.g., anacardic acid, curcumin, epigallocatechin-3-gallate, garcinol, spermidine) or deacetylase activators (e.g., nicotinamide, resveratrol), and that are highly efficient inducers of autophagy in vitro and in vivo, in rodents. Another common characteristic of these agents is their capacity to reduce aging-associated diseases and to confer protective responses against ischemia-induced organ damage. Hence, we classify them as “caloric restriction mimetics” (CRM). Here, we speculate that CRM may mediate their broad health-improving effects by triggering the same molecular pathways that usually are elicited by long-term caloric restriction or short-term starvation and that imply the induction of autophagy as an obligatory event conferring organismal, organ- or cytoprotection.

Keywords: acetyl-coenzyme A, acetyl transferase, acetylation, deacetylase, deacetylation

Abbreviations: AcCoA, acetyl coenzyme A; CRM, caloric restriction mimetics; EGCG, epigallocatechin-3-gallate

Macronutrient scarcity constitutes one the most common inducers of macroautophagy (to which we refer as autophagy). In teleological terms, the prime finality of autophagy is the mobilization of the cell’s reserves and hence the conversion of macromolecules into energy-rich substrates that are required for maintaining essential functions, the avoidance of cell death, and the adaptation to stress.^1,2 Starvation of human cells (by their culturing in nutrient-free medium) or starvation of mice (by removing food from the cages for 24 h, granting access only to water) results in the preponderant depletion of 1 intracellular metabolite, acetyl coenzyme A. Kinetic experiments performed in vitro, on human cell lines cultured in the absence of nutrients indicate that depletion of the nucleocytosolic pool of AcCoA occurs before ATP is reduced, NADH is oxidized, and amino acids are depleted from the intracellular metabolome, at the same time as autophagy becomes detectable.³ Specific depletion of cytosolic AcCoA pools by inhibition of its mitochondrial synthesis (from pyruvate, branched amino acids or lipid ß-oxidation) or its transfer from the mitochondrial matrix to the cytosol (which requires the conversion of AcCoA to citrate in the matrix, the export of citrate by the citrate carrier, and final conversion of citrate to AcCoA by ACLY [ATP citrate lyase]) is sufficient to induce autophagy even in conditions in which ATP and NADH levels are normal.³ Moreover, external provision of AcCoA (e.g., by microinjection of the metabolite into the cytoplasm) is sufficient to prevent starvation-induced autophagy.³

Altogether, these observations point to the idea that starvation causes autophagy because it results in the early depletion of AcCoA.^3,4 This adds to other mechanisms through which caloric restriction or starvation can stimulate autophagy, namely the induction of the deacetylase activity of sirtuins (as a result of changing NADH/NAD⁺ ratios and increased SIRT1 expression),⁵ the activation of AMPK activity (as a result of changing ATP/ADP ratios),⁶ and the inhibition of MTORC1 (as a result of amino acid depletion).⁷ The available evidence indicates that the principal acetylransferase that is required for the AcCoA-mediated repression of autophagy is EP300,³ an acetyltransferase that can transfer acetyl groups from AcCoA to autophagy core proteins including ATG5, ATG7, ATG12, and LC3, thus inhibiting their pro-autophagic activity.⁸ Specific AcCoA depletion or direct inhibition of EP300 by genetic or pharmacological methods causes the rapid activation of AMPK and the inactivation of MTORC1, suggesting that these nutrient sensors are functionally connected to each other.³

The aforementioned results suggest a strategy for the identification of drugs that mimic the effects of starvation with regard to the depletion of AcCoA and the consequent deacetylation of cellular proteins. Within this framework, there would be 3 categories of “caloric restriction mimetics” (CRMs): (i) agents that reduce the concentration of cytosolic AcCoA; (ii) inhibitors of autophagy-repressive acetyltransferases including EP300; and (iii) activators of autophagy-stimulatory deacetylases including SIRT1.⁹ It is reasonable to expect that CRMs falling in one of these 3 categories would elicit the same biochemical pathways that are usually stimulated by starvation and hence induce an autophagic response that is exempt from major toxicological side effects (Fig. 1).

Figure 1.

Caloric restriction and its pharmacological mimetics. (A) General outline of the mechanisms of health improvement by caloric restriction (CR). (B) Molecular mechanism of autophagy induction by CR. (C) Mechanism of action of caloric restriction mimetics (CRMs). (D) Hypothetical mechanisms of anti-aging effects of CR and CRMs.

Indeed there is a vast literature showing that there are multiple CRMs that can be used in humans. As an example, hydroxycitrate, an inhibitor of ACLY that causes cytosolic AcCoA depletion, protein deacetylation, and massive autophagy in all studied organs in mice,³ is also an over-the-counter weight loss agent commercialized in the US.¹⁰ A variety of agents known to inhibit EP300 are being used in traditional medicine or are obtainable without a prescription. This applies to anacardic acid (6-pentadecyl-salicylic acid from the nutshell of the cashew, Anacardium occidentale),¹¹ curcumin (from the South Asian spice turmeric, Curcuma longa, one of the principal ingredients of curry powder),¹² and garcinol (from the fruit of the Kokum tree, Garcina indica).¹³ All these agents are also potent inducers of protein deacetylation and autophagy when added to cultured human cells.³ Similarly, epigallocatechin-3-gallate (EGCG, one of the major active compounds contained in green tea) can inhibit a range of acetyltransferases¹⁴ including EP300.¹⁵ Spermidine (a polyamine contained in all organisms, but found at particular high concentrations in some health-related products such as durian fruit, fermented soybeans, and wheat germs) was first characterized as a histone acetyl transferase inhibitor.¹⁶ Spermidine potently induces protein deacetylation and autophagy in vivo, in mice or in cultured human cells.¹⁷ Finally, resveratrol exemplifies a widely used over-the-counter drug that can stimulate the deacetylase activity of SIRT1, thereby causing general protein deacetylation and autophagy.^17-19 Nicotinamide is another potential SIRT1 activator that is sold over the counter in the US²⁰ and that induces autophagy in rodents.²¹

What could be the therapeutic indications for the use of such CRMs? CR or intermittent fasting are known for their wide life-span-extending and health-improving effects that can be measured in an objective fashion in multiple model organisms including rodents²² and primates.²³ Beyond their capacity to reduce aging and aging-associated pathologies (such as neurodegeneration, type-2 diabetes, and cancer), fasting also has an important preconditioning effect, protecting different organs from ischemic insult. This applies to the heart^24,25 brain,²⁶ liver,²⁷ and kidney.²⁸ There is emerging evidence that autophagy is involved in starvation-mediated organ protection.^25,28 Moreover, fasting can reduce the subjective and objective toxicity of cytotoxic anticancer chemotherapies, both in humans and in mouse models, at the same time that it improves treatment outcome in mice.^29,30 It is tempting to speculate that CRMs could be used for the same therapeutic indications in which fasting has proven to be useful. In accord with this idea, several CRMs can increase the health span and life span of rodents (as demonstrated for EGCG, spermidine and resveratrol),^31-33 reducing the advancement of neurodegenerative diseases (as shown for spermidine, nicotinamide and resveratrol), likely through their capacity to induce autophagy.^34,35 Moreover, several CRMs (including EGCG and resveratrol) have potent preconditioning effects in ischemia,^36,37 which, at least on theoretical grounds, might be due to the induction of cytoprotective autophagy.³⁸

Future studies should address the following major questions:

• Do all beneficial effects of CRMs result from the induction of autophagy, or are there any autophagy-independent effects? This question should be addressed in suitable mouse models in which autophagy can be genetically inhibited in a spatially- and temporarily-controlled fashion.
• Which are the CRMs that are optimally suitable for a precise indication (anti-aging effects, neuro-, cardio-, hepatoprotection, adjuvant treatment of anticancer chermotherapy), comparing them in preclinical tests to their positive control, that is fasting or caloric restriction? Ideally, this problem should be addressed in a systematic fashion involving the simultaneous comparison of multiple CRMs.
• Is it possible to develop more specific CRMs, such as inhibitors of EP300 that fail to affect other acetyltransferases or truly specific inhibitors of ACLY, with the scope of optimizing their efficacy?
• Is it possible to combine several mechanistically distinct CRMs (such as those depleting AcCoA, inhibiting acetyltransferases, or activating deacetylases) to obtain synergistic effects for maximal induction of therapy-relevant autophagy?

We surmise that responding to these questions will boost the rational development of new indications for old drugs, as well as the development of novel CRMs with a broad therapeutic potential.

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Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

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Funding

GK is supported by the Ligue contre le Cancer (équipe labelisée); Agence Nationale de la Recherche (ANR); Association pour la recherche sur le cancer (ARC); Cancéropôle Ile-de-France; Institut National du Cancer (INCa); Fondation Bettencourt-Schueller; Fondation de France; Fondation pour la Recherche Médicale (FRM); the European Commission (ArtForce); the European Research Council (ERC); the LabEx Immuno-Oncology; the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); the SIRIC Cancer Research and Personalized Medicine (CARPEM); and the Paris Alliance of Cancer Research Institutes (PACRI). FM is supported by FWF grants LIPOTOX, P23490-B12, I1000 and P24381-B20.

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Abstract

Hundreds of millions of people now die over the age of 80 years primarily due to twentieth century progress in hygiene, chemotherapy, and immunology. With a longer average lifespan, the need to improve quality of life during the latter decades is more compelling. “Aging — The Epidemic of the New Millenium,” a recent international conference (Monte Carlo, June 17–18, 2000), showed with peculiar clarity that a safe and efficient drug strategy to slow the age‐related decay of brain performance is still missing. This review summarizes the physiologic and pharmacologic arguments in favor of a peculiar lifelong prophylactic medication with reasonable chances to keep in check brain aging and decrease the precipitation of age‐related neurological diseases.

SUMMARY AND CONCLUSIONS

The specific brain activation mechanism (“drive”) that ensures that living beings surmount every obstacle to reach a goal, even if life is in the balance, roots in the existence of “enhancer‐sensitive” neurons in the brain that are ready to increase their activity with lightning speed in response to endogenous “enhancer” substances, of which phenylethylamine (PEA) and tryptamine are the presently known examples. PEA and tryptamine enhance the impulse‐propagation‐mediated release of catecholamines and serotonin in the brain (CAE/SAE effect). This is the best model for studying the enhancer regulation in the mammalian brain, which starts working at the discontinuation of breast feeding. Weaning is the beginning of the developmental (“uphill”) period of life and is characterized by significantly higher brain activity levels that last until the sexual hormones dampen this regulation, thereby terminating the uphill period. This is the prelude of the postdevelopmental (“downhill”) phase of life and the beginning of the slow brain aging process from which there is no escape until natural death.

It has been proposed that enhancer compounds can delay the natural age‐related deterioration of brain performance and keep the brain on a higher activity level during postdevelopment longevity. PEA, a substrate of MAO‐B, and tryptamine, a substrate of MAO‐A, are rapidly metabolized, short‐acting endogenous enhancer compounds. PEA and its long‐acting derivatives, amphetamine and methamphetamine, which are not metabolized by MAO, are enhancer substances at low concentrations but also potent releasers of catecholamines and serotonin from their pools at higher concentrations. The catecholamine‐releasing effect masked for decades the enhancer property of these compounds.

(‐)Deprenyl (selegiline) is the first PEA derivative free of the catecholamine‐releasing property and made possible the discovery of the enhancer regulation in the brain. This drug is presently the only clinically used enhancer compound. (‐)Deprenyl is also a highly potent, selective inhibitor of MAO‐B and is metabolized to amphetamines. Tryptamine is an endogenous enhancer substance free of the catecholamine/serotonin‐releasing property. The newly developed tryptamine derivative (‐)BPAP is the first highly selective enhancer substance. It is also much more potent than (‐)deprenyl.

Enhancer substances that keep the enhancer‐sensitive neurons on a higher activity level slow the age‐related deterioration of the mammalian brain. Maintenance of rats on (‐)deprenyl during post‐developmental longevity slows the age‐related decline of sexual and learning performances and prolongs life significantly. Patients with early Parkinson’s disease who are maintained on (‐)deprenyl need levodopa significantly later than their placebo‐treated peers and they live significantly longer when on levodopa plus (‐)deprenyl than patients on levodopa alone. In patients with moderately severe impairment from Alzheimer’s disease, treatment with (‐)deprenyl slows the progression of the disease.

(‐)BPAP is an especially promising prophylactic antiaging compound that may provide the opportunity to shift the functional constellation of the brain during postdevelopmental longevity towards the one characteristic to the uphill period of life. According to the available experimental and clinical data, it is reasonable to expect that daily administration of an enhancer drug [e.g., (‐)deprenyl 1 mg or (‐)BPAP 0.1 mg] from sexual maturity until death will improve quality of life in the latter decades, shift the time of natural death, decrease the precipitation of age‐related depression, and reduce the prevalence of Parkinson’s disease and Alzheimer’s disease.

Keywords: Selegiline, Deprenyl, Antiaging drugs, BPAP

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Selected References

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Once the mice were weaned at around four weeks after birth, the researchers moved them into a hypoxic chamber with an oxygen concentration of just 11 percent, the equivalent of the oxygen levels at the base of Mount Everest.

Rather than decreased barometric pressure — the reason for such low oxygen tension at high altitudes — the hypoxic chamber’s low oxygen content was caused by dilution with nitrogen gas.

The median life span of these mice living at normal 21 percent oxygen was just shy of 16 weeks. However, animals housed in the hypoxic chamber lived to about 24 weeks, on average, or about 50 percent longer than expected.

The maximum life span of these animals also increased under low-oxygen conditions — by about 30 percent, or about 31 weeks, compared with 26-week life spans of their peers living in normal oxygen concentrations.

Life span wasn’t the only outcome that changed for the animals residing under oxygen restriction, Rogers explained.

Mice living in the reduced oxygen environment also preserved neurologic function longer, as measured by their performance on a standard test of coordination and strength.

Seeking to understand the mechanism behind these effects, the researchers examined food intake to see if the animals ate less, since caloric restriction has proved to be a potent life span extender in multiple animal models.

To the researchers’ surprise, mice living in the hypoxic chamber ate slightly more food than those living under normal oxygen concentrations. A search for unusual gene activity, DNA damage, or changes in signaling pathways in the oxygen-restricted mice turned up some tantalizing clues but no definitive answers, Rogers said.

Future studies, he added, should examine whether oxygen restriction can similarly extend life span in wild-type mice, should seek to define what mechanisms might be responsible for the life-extending effects of restricted oxygen, and determine whether these mechanisms affect all organs.

Authorship, funding, disclosures

Additional authors included Hong Wang, Timothy Durham, Jonathan Stefely, Norah Owiti, Andrew Markhard, Lev Sandler, and Tsz-Leung To.

This work was funded by a gift from the J. Willard and Alice S. Marriott Foundation to Mootha. Mootha is an Investigator of the Howard Hughes Medical Institute. Rogers is supported by the Parker B. Francis Family Foundation Fellowship.

Mootha is on the scientific advisory board of 5am Ventures. He is listed as an inventor on patents filed by Massachusetts General Hospital on the therapeutic uses of hypoxia.

Study in mice suggests that oxygen restriction could extend life span
by CHRISTEN BROWNLEE May 23, 2023 Research
4 min read

At a glance:

• Living in a low-oxygen environment extended life spans, preserved neurologic function in mice.
• Findings add to a growing body of research showing oxygen restriction may ward off neurologic decline and extend life span in animal models.
• Mechanisms behind the protective effects of oxygen deprivation remain to be elucidated.

A strain of mice born with abnormally short life spans defied expectations and lived 50 percent longer than expected when put in an environment with low oxygen roughly equivalent to a Mount Everest base camp, Harvard Medical School scientists report in a new study.

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The findings, published May 23 in PLOS Biology, add to a growing list of approaches shown to lengthen life in animal models and provide the first demonstration that oxygen restriction could extend life span in a mouse model of aging.

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Epidemiological observations have offered tantalizing clues to a curious phenomenon — people who reside at high altitudes tend to live longer and appear less prone to developing certain diseases.

In the new study, researchers sought to determine whether they could replicate this finding in animals.

“Epidemiological studies have hinted that populations that live at higher altitudes tend to live longer and stay healthier as they age. We wanted to test whether, in a more controlled setting, restricting oxygen appears to do the same in our mouse model of aging”,” said study senior author Vamsi Mootha, professor of systems biology in the Blavatnik Institute at Harvard Medical School.

Since time immemorial, humans have sought to cheat — or at least delay — death by extending their natural life spans, said study first author Robert Rogers, a postdoctoral researcher in the Mootha Lab.

This quest may be within closer reach with a mounting body of research over the past few decades that has identified a number of ways that significantly lengthen the lives of cells in petri dishes and common lab animals such as roundworms, fruit flies, and mice.

These strategies include caloric restriction and use of the diabetes medication metformin, the immunosuppressive drug rapamycin, and aspirin — all of them in various stages of testing in animal models and humans.

Some studies have suggested that oxygen restriction — limiting the concentration of oxygen in the ambient air at a level significantly below that at sea level, about 21 percent — can also extend life span in a variety of models, including fruit flies, worms, yeast, and mammalian cells in lab dishes. Thus far, however, oxygen restriction has remained unexplored in mammalian aging.

To test this idea, Mootha, Rogers, and their colleagues worked with a strain of mice that age prematurely. These animals succumb to age-related diseases at about 3 or 4 months of age, compared with normal, or “wild type” mice, who live about two years.

Once the mice were weaned at around four weeks after birth, the researchers moved them into a hypoxic chamber with an oxygen concentration of just 11 percent, the equivalent of the oxygen levels at the base of Mount Everest.

Rather than decreased barometric pressure — the reason for such low oxygen tension at high altitudes — the hypoxic chamber’s low oxygen content was caused by dilution with nitrogen gas.

The median life span of these mice living at normal 21 percent oxygen was just shy of 16 weeks. However, animals housed in the hypoxic chamber lived to about 24 weeks, on average, or about 50 percent longer than expected.

The maximum life span of these animals also increased under low-oxygen conditions — by about 30 percent, or about 31 weeks, compared with 26-week life spans of their peers living in normal oxygen concentrations.

Life span wasn’t the only outcome that changed for the animals residing under oxygen restriction, Rogers explained.

Mice living in the reduced oxygen environment also preserved neurologic function longer, as measured by their performance on a standard test of coordination and strength.

Seeking to understand the mechanism behind these effects, the researchers examined food intake to see if the animals ate less, since caloric restriction has proved to be a potent life span extender in multiple animal models.

To the researchers’ surprise, mice living in the hypoxic chamber ate slightly more food than those living under normal oxygen concentrations. A search for unusual gene activity, DNA damage, or changes in signaling pathways in the oxygen-restricted mice turned up some tantalizing clues but no definitive answers, Rogers said.

Future studies, he added, should examine whether oxygen restriction can similarly extend life span in wild-type mice, should seek to define what mechanisms might be responsible for the life-extending effects of restricted oxygen, and determine whether these mechanisms affect all organs.

Authorship, funding, disclosures

Additional authors included Hong Wang, Timothy Durham, Jonathan Stefely, Norah Owiti, Andrew Markhard, Lev Sandler, and Tsz-Leung To.

This work was funded by a gift from the J. Willard and Alice S. Marriott Foundation to Mootha. Mootha is an Investigator of the Howard Hughes Medical Institute. Rogers is supported by the Parker B. Francis Family Foundation Fellowship.

Mootha is on the scientific advisory board of 5am Ventures. He is listed as an inventor on patents filed by Massachusetts General Hospital on the therapeutic uses of hypoxia.