Aging and Cancer Extra Edition – Part 1 What Are “Anti-Aging Drugs”? An Introductory Guide from Metformin and mTOR to Senolytics and “Rejuvenation”

Introduction: Why Are “Anti-Aging Drugs” a Hot Topic Now?

When you hear “anti-aging drugs” or “rejuvenation pills,” you might imagine dubious supplements or flashy beauty ads. However, what many academic groups, pharmaceutical companies, and biotech startups are seriously pursuing today is quite different: scientifically grounded medicines that target the biology of aging.

There are two important points to keep in mind:

• Aging itself is not yet recognized as a “disease” by regulators.
• However, drugs that modulate core mechanisms of aging may have broad effects on age-related diseases (diabetes, cardiovascular disease, dementia, cancer, etc.).

In this series, we have explored the links between aging and cancer from molecular mechanisms to clinical practice and public health. In this first Extra Edition, building on that foundation, we will address, at an introductory level:

• What do we actually mean by “anti-aging drugs”?
• Which biological pathways do they target?
• What has been shown in mice, and what can we realistically say in humans?
• How do scientific “aging interventions” differ from typical “anti-aging supplements”?

1. What Exactly Are “Anti-Aging Drugs”?

1-1. Aging Is Not Yet a Recognized Disease

First, some regulatory context. At present, agencies such as the FDA and PMDA do not recognize:

• “Aging” or “senescence” as a standalone disease entity.

As a result:

• It is not currently possible to obtain formal approval for a drug with “aging” itself as the indication.

At the same time, aging research has identified a number of shared mechanisms, often summarized as the “hallmarks of aging”, including:

• DNA damage and repair defects
• Telomere shortening
• Mitochondrial dysfunction
• Epigenetic alterations
• Cellular senescence
• Chronic low-grade inflammation

These hallmarks are tightly linked to age-related diseases such as cancer, cardiovascular disease, diabetes, and neurodegeneration.

1-2. A Practical Definition of “Anti-Aging Drugs”

Given this background, it is practical to define current “anti-aging drugs” as follows:

• Drugs that target fundamental biological mechanisms of aging (the hallmarks of aging), and thereby have the potential to influence the onset, progression, or treatment response of age-related diseases.

In other words:

• They are not drugs “approved for aging” as an indication.
• Instead, they are developed and approved for specific conditions—such as diabetes, heart failure, fibrosis, or frailty—while mechanistically acting on aging pathways.

This is the core of what we currently mean by “anti-aging drugs” in a real-world, regulatory sense.

2. Five Major Categories of Aging-Targeted Interventions

There are many candidate interventions, but from an introductory viewpoint, we can group them into five broad categories:

• ① mTOR and metabolic modulators (rapamycin, metformin, GLP-1 agonists, etc.)
• ② Senolytics and senomorphics (drugs that eliminate or modulate senescent cells)
• ③ NAD⁺, sirtuins, and mitochondrial modulators
• ④ Regenerative approaches: stem cells, MSCs, plasma factors
• ⑤ Reprogramming and partial “rejuvenation”

We will walk through these categories one by one, focusing on mechanisms and concepts rather than investment or hype.

3. Category ①: mTOR and Metabolic Pathways – Rapamycin, Metformin, GLP-1

3-1. mTOR Inhibition: A Classic Longevity Target

mTOR is a central regulator of growth, protein synthesis, and metabolism—often described as a “nutrient sensor” that turns on growth programs when resources are abundant. Rapamycin and its analogs (“rapalogs”) inhibit mTOR.

In multiple animal models, including mice, rapamycin has been shown to:

• Extend lifespan even when treatment starts in midlife
• Delay the onset of various age-related pathologies

As a result, rapamycin is often cited as one of the most robust pharmacologic longevity interventions in preclinical research.

In humans, however:

• Clinically used doses (for organ transplantation or cancer) carry significant risks—such as infections and metabolic side effects.

This has led to interest in:

• Low-dose or intermittent dosing to see whether immune function, frailty, or infection resistance can be improved with acceptable safety.

Such trials are ongoing but still in relatively early stages.

3-2. Metformin: The Most Famous Longevity Candidate Among Diabetes Drugs

Metformin is a first-line treatment for type 2 diabetes. Large observational studies have suggested that:

• Diabetic patients on metformin may have lower all-cause mortality than non-diabetic individuals not taking the drug.

These findings, though not definitive, drew attention to metformin as a potential “longevity drug” in humans.

Mechanistically, metformin appears to modulate aging-related pathways through:

• Activation of AMPK
• Effects on mitochondrial metabolism and oxidative stress
• Possible reduction of chronic inflammation

This led to the proposal of the TAME (Targeting Aging with Metformin) trial, designed to evaluate whether metformin can delay multiple age-related diseases in humans. The concept remains influential, even as details of trial implementation continue to evolve.

3-3. GLP-1 Receptor Agonists: From Obesity Treatment to “Metabolic Rejuvenation”

GLP-1 receptor agonists and related agents were originally developed as diabetes medications. Recently, they have gained widespread attention as powerful treatments for obesity and cardiometabolic risk.

Large clinical trials have shown:

• Substantial weight loss
• Reduction in cardiovascular events
• Benefits in kidney function and liver fat in some studies

Although they are not classic “anti-aging drugs,” they can be viewed as interventions that:

• Correct accelerated “metabolic aging” driven by obesity and insulin resistance.

From the perspective of aging and cancer, GLP-1 drugs may potentially:

• Reduce the risk of obesity-associated cancers
• Improve treatment tolerance by improving physical and metabolic reserve

These ideas are still under investigation, but the concept of “metabolic rejuvenation” is increasingly discussed.

4. Category ②: Senolytics and Senomorphics – Managing Senescent Cells

4-1. What Are Senescent Cells?

Cellular senescence is a state in which cells permanently stop dividing but do not die. Senescent cells typically:

• Remain metabolically active
• Secrete pro-inflammatory cytokines and other factors (the SASP: senescence-associated secretory phenotype)

In youth, senescence can play helpful roles in:

• Tumor suppression
• Wound healing and tissue remodeling

However, when senescent cells accumulate with age, they may contribute to:

• Chronic inflammation
• Fibrosis
• Organ dysfunction

and are believed to facilitate the development of age-related diseases, including cancer.

4-2. Senolytics: Drugs That Selectively Eliminate Senescent Cells

Senolytics are designed to exploit survival pathways that senescent cells rely on—such as BCL-2 family proteins—to selectively induce senescent cell death, while sparing normal cells.

Examples include:

• Combining dasatinib (a cancer drug) with quercetin (a plant polyphenol)
• Newer small molecules that selectively inhibit BCL-xL or related targets

Clinical trials are underway in conditions such as:

• Idiopathic pulmonary fibrosis
• Diabetic complications
• Ophthalmologic diseases (e.g., diabetic macular edema)

The hope is that clearing senescent cells will reduce inflammation and improve tissue function; however, large-scale human data are still limited.

4-3. Senomorphics: Reprogramming the Behavior of Senescent Cells

In contrast to senolytics, senomorphics do not necessarily kill senescent cells. Instead, they aim to:

• Reduce harmful SASP factors
• Shift senescent cells toward a less inflammatory, less damaging phenotype

Because senescent cells also have physiological roles, such as in wound healing, an overly aggressive removal strategy could be harmful. Senomorphics are therefore an attractive option when:

• The goal is to “tune down” senescent cell toxicity rather than eliminate them altogether.

5. Category ③: NAD⁺, Sirtuins, and Mitochondria

5-1. What Is NAD⁺ and Why Does It Matter?

NAD⁺ is a cofactor essential for energy metabolism and DNA repair. Levels of NAD⁺ appear to decline with age in multiple tissues. Restoring NAD⁺ has been proposed as a way to:

• Improve mitochondrial function
• Support DNA repair and genomic stability
• Rebalance cellular metabolism

Common NAD⁺ precursors include:

• Nicotinamide riboside (NR)
• Nicotinamide mononucleotide (NMN)

These are widely available as supplements, and human studies have shown that they can safely raise NAD⁺ levels in the short term. However, robust evidence that they meaningfully slow aging or alter disease outcomes in humans is still lacking.

5-2. Sirtuins and the Post-Resveratrol Landscape

Sirtuins are enzymes that regulate epigenetic states and metabolism, often described as “longevity genes.” Resveratrol, a polyphenol, was once widely touted as a sirtuin activator and potential anti-aging compound.

Subsequent research has shown that:

• Resveratrol’s effects are complex and not as specific as initially thought.
• Human clinical data have not confirmed strong, consistent anti-aging benefits.

As a result, enthusiasm has shifted toward:

• Second- and third-generation sirtuin modulators with higher specificity and better pharmacokinetics

Some of these are in clinical trials for metabolic and neurodegenerative disorders, but it is still early days in terms of definitive evidence.

6. Category ④: Regenerative Approaches – Stem Cells, MSCs, and Plasma Factors

6-1. Mesenchymal Stem Cell (MSC) Therapy

Mesenchymal stem cells (MSCs), whether autologous or allogeneic, are used to:

• Suppress harmful inflammation
• Promote tissue repair

Clinical trials have been conducted in conditions such as:

• Osteoarthritis
• Heart failure
• Chronic lung diseases

From an aging perspective, MSCs are less about reversing aging per se and more about:

• Repairing and stabilizing tissues already damaged by age-related processes.

6-2. Plasma Factors: “Young Blood” and “Old Blood”

In mouse parabiosis experiments—where the circulatory systems of a young and an old animal are joined—researchers have observed that:

• Young blood can partially rejuvenate aged tissues
• Old blood can impair function in younger animals

These findings sparked interest in:

• Drugs that modulate plasma composition
• Plasma exchange protocols as potential aging interventions

At the same time, services offering “young donor plasma” for anti-aging purposes have raised serious ethical and safety concerns. Distinguishing rigorous clinical research from speculative commercial offerings is especially important in this area.

7. Category ⑤: Reprogramming and Partial “Rejuvenation”

7-1. Yamanaka Factors and Full Reprogramming

The Yamanaka factors (Oct4, Sox2, Klf4, c-Myc) can reprogram differentiated cells into induced pluripotent stem cells (iPSCs). This involves:

• Profound resetting of the epigenome to a more “youthful” state

However, applying full reprogramming in vivo would be dangerous because:

• It can lead to loss of normal cell identity
• It increases the risk of tumor formation (e.g., teratomas)

7-2. Partial Reprogramming: Gently Reversing Some Aspects of Aging

To mitigate these risks, researchers are exploring partial reprogramming, in which Yamanaka factors or related transcription factors are:

• Expressed transiently and at controlled levels
• Used to nudge aged cells toward a younger epigenetic state without fully resetting identity

In mouse models, partial reprogramming has shown promising effects in:

• Optic nerve injury and age-related visual decline
• Functional improvements in kidney, muscle, and skin in some studies

Nevertheless, key challenges remain:

• Potential cancer risk
• Uncertain long-term safety
• Decisions about using systemic versus localized delivery

At this point, partial reprogramming is best regarded as a high-potential but still experimental “rejuvenation technology” rather than a clinical anti-aging therapy.

8. Lifespan Extension in Mice vs. Interpretation in Humans

8-1. What Animal Studies Tell Us

Many candidate anti-aging interventions have been shown in animals to:

• Extend lifespan
• Delay the onset of age-related diseases

These results provide strong proof-of-concept that:

• Modulating hallmarks of aging can, in principle, alter lifespan and healthspan.

8-2. Why Lifespan Trials in Humans Are So Difficult

In humans, demonstrating an effect on lifespan directly would require:

• Follow-up over decades
• Very large numbers of participants

Such trials are logistically and financially challenging, and ethically complex.

Therefore, human trials typically rely on:

• Delay of specific age-related diseases (e.g., cardiovascular events, dementia, cancer)
• Changes in aging biomarkers (e.g., epigenetic clocks, frailty indices)

as endpoints to infer potential effects on aging.

Practically speaking:

• In mice, we may see headlines like “Drug X extended lifespan by 20%.”
• In humans, we are usually talking about “Drug Y modestly improved aging biomarkers or reduced risk of condition Z over several years.”

Recognizing this difference helps us interpret media reports more realistically.

9. Scientific Aging Drugs vs. “Anti-Aging Supplements”

9-1. Differences in Evidence Standards

The marketplace is full of supplements labeled as “anti-aging” or “rejuvenating.” Often:

• Claims are based mainly on animal or cell culture experiments.
• There are few, if any, rigorous randomized controlled trials in humans.

By contrast, scientific aging-targeted drugs and serious clinical candidates undergo:

• Detailed safety assessments including dose, side effects, and drug–drug interactions
• Carefully designed clinical trials approved by ethics committees and regulatory agencies
• Statistical evaluation of efficacy for specific diseases or aging-related endpoints

The gap in evidence quality between these two categories is large, even if the marketing language sometimes sounds similar.

9-2. The Risks of Self-Medication

Particular caution is needed when people consider using:

• Prescription drugs such as metformin or rapamycin
• Cancer drugs or immunosuppressants

solely for “longevity” or “anti-aging” without medical supervision. Potential risks include:

• Severe side effects (e.g., lactic acidosis, hypoglycemia, serious infections)
• Dangerous interactions with other medications

Most aging-targeted drugs are not “safe for everyone at any dose.” They should be considered:

• Pharmacologic tools with real benefits and non-trivial risks, to be used judiciously under medical guidance.

10. Risks and Open Questions: Including the Cancer Connection

10-1. Will Anti-Aging Drugs Reduce or Increase Cancer Risk?

From a cancer perspective, aging interventions can cut both ways:

• Some may lower cancer risk by reducing chronic inflammation, metabolic stress, or DNA damage.
• Others could increase risk if they interfere with tumor-suppressive mechanisms or enhance proliferative capacity.

For example:

• Excessive or poorly controlled reprogramming may destabilize cell identity and promote tumorigenesis.
• Over-suppressing immune function may weaken tumor immune surveillance.

Thus, it is overly simplistic to assume that:

• “Slowing aging will automatically reduce all cancers.”

The relationship is more nuanced and must be evaluated drug by drug, context by context.

10-2. Long-Term Safety and Regulatory Hurdles

Many anti-aging strategies are envisioned for:

• Relatively healthy older adults
• Long-term or even lifelong use

This raises formidable questions about:

• Long-term effects on cancer, cardiovascular disease, and other major outcomes
• Unanticipated side effects on immune, endocrine, skeletal, or nervous systems

Regulators understandably require robust evidence before approving drugs for such broad, long-duration indications.

The fact that “true anti-aging drugs” are slow to reach the clinic does not mean the science is stagnant. Rather, it reflects the inherently high bar for long-term safety and efficacy in this field.

11. How Should We, as Individuals, Engage with Anti-Aging Drug Research?

11-1. Start with Lifestyle and Optimal Use of Existing Therapies

For most people today, the most impactful—and evidence-based—steps toward healthier aging are still:

• ① Updating lifestyle: avoiding tobacco, maintaining physical activity, eating a balanced diet, and protecting sleep and mental health.
• ② Properly treating existing conditions such as diabetes, hypertension, and dyslipidemia under medical supervision.

On top of this foundation, it may make sense to:

• Use drugs like metformin or GLP-1 agonists appropriately when indicated for metabolic disease, in consultation with a physician.

Doing so may, as a side effect, slow some aspects of biological aging by reducing metabolic stress and improving organ function—even if “anti-aging” is not the formal indication.

11-2. Reading the News with Balanced Expectations

When you see headlines about “rejuvenation drugs” or “reversing aging,” it is helpful to ask:

• Was the study done in animals or humans?
• If in humans, how many participants and for how long?
• What endpoints were measured—lifespan, disease incidence, or aging biomarkers?
• Is this a dietary supplement or a regulated drug candidate?
• Which hallmark of aging is being targeted?

Even this simple checklist can help you steer between:

• Over-optimistic hype (“This pill will make you young forever!”)
• And blanket skepticism (“Everything about anti-aging is nonsense.”)

and instead evaluate each claim on its own merits.

My Thoughts

The topic of anti-aging drugs easily attracts sensational language, and “rejuvenation” becomes a magnet for both hope and skepticism. Yet, if we look more closely at what researchers and clinicians are actually doing, the reality is much more modest and methodical. A lifespan extension result in mice is typically followed by years of dissecting mechanisms, defining safe doses, and designing clinical trials that may take decades to read out in humans. That slow, careful process often sits in stark contrast to the immediacy of media headlines.

At the same time, this work offers an opportunity to rethink aging and cancer—not as separate fates, but as intertwined processes that can be influenced at multiple levels. Reframing diabetes and obesity treatments as “metabolic aging interventions,” or viewing cancer survivorship through the lens of therapy-induced aging, can already change how we design care pathways, health policies, and even individual life plans.

In the next Extra Edition, we will build on the mechanisms outlined here and look at specific biotech and pharmaceutical companies developing aging-targeted drugs—translating abstract concepts into concrete projects and pipelines, while still keeping the discussion accessible for non-specialists.

This article has been edited by the Morningglorysciences team.

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