# Can We Slow Down Aging? Inside the Push to Extend "Healthspan"

Two groups of leading aging researchers argue that modern medicine's strategy of treating diseases one at a time — heart failure today, cancer tomorrow, arthritis next year — is failing older adults, and that we should instead target the aging process itself. Evidence from animal studies, human genetics, and exceptionally long-lived people shows that aging is not fixed; it can be slowed. The authors call for new functional tests in animals, better collaboration between laboratory and clinical researchers, and a fundamental shift in how aging research is funded and organized. This article translates their two-part commentary from *Nature* into plain language for patients and families.

# Can We Slow Down Aging? Inside the Push to Extend "Healthspan"

## Table of Contents

- Key Points
- Background: Why This Research Matters
- The Problem: Aging Comes as a Package
- What Animal Studies Have Taught Us
- Why Aging Is Malleable: Evidence from Humans
- Drugs and Diets on the Horizon
- The Demographic Challenge Ahead
- A Major Roadblock: Funding and Focus
- How We Measure Aging: The Power of Simple Tests
- The Gap: What's Missing in Animal Studies
- Building Better Tools to Track Aging
- Recommendations: A Roadmap Forward
- What This Means for Patients Today
- Limitations and Open Questions
- Frequently Asked Questions
- Source Information

## Key Points

- Aging is malleable, not fixed, according to animal and human evidence.
- Over 70% of adults over 65 have two or more chronic conditions; aging is a common risk factor.
- Simple tests like grip strength and walking speed predict disability and survival.
- Rapamycin, metformin, and resveratrol extend lifespan in animals but are unproven for humans.
- Prevention should start earlier in life; diet and exercise remain effective for healthy aging.

## Background: Why This Research Matters

In July 2014, the prestigious journal *Nature* published a special commentary asking a bold question: What if we stopped trying to cure individual diseases of old age — and instead targeted aging itself?

The commentary brings together two teams of scientists. The first, led by Dr. Luigi Fontana (Washington University in St. Louis and Brescia University, Italy), Dr. Brian K. Kennedy (Buck Institute for Research on Aging), and Dr. Valter D. Longo (University of Southern California), argues that we must "prepare for human testing" of anti-aging interventions. The second, led by Dr. Douglas Seals (University of Colorado Boulder) and Dr. Simon Melov (Buck Institute), explains why we need to "track function in ageing animals" to bridge the gap between laboratory discoveries and real patient care.

The stakes are enormous. The authors project that by 2050, the number of people over 80 will triple globally — and the number over 60 will be five times what it was in 1950. As Dr. Fontana's team puts it, "These demographics could come at great cost to individuals and economies."

## The Problem: Aging Comes as a Package

Here's the core insight: **the problems of old age come as a package.** More than 70% of people over 65 have two or more chronic conditions at the same time — conditions like:

- Arthritis
- Diabetes
- Cancer
- Heart disease
- Stroke

Current medicine treats these one at a time. A patient might see a cardiologist for heart failure, an oncologist for cancer, and an endocrinologist for diabetes — as if these were unrelated problems.

But the evidence suggests otherwise. Studies of diet, genes, and drugs indicate that **delaying one age-related disease probably staves off others**. That's because aging itself is the common risk factor. The authors explain that at least a dozen molecular pathways seem to "set the pace of physiological ageing" — the biological clocks that determine how quickly our bodies accumulate damage.

This has led researchers to coin an important term: **healthspan** — the number of years lived without chronic, age-related disease. Extending lifespan, they argue, is only worthwhile if it also extends healthspan.

## What Animal Studies Have Taught Us

Decades of animal research have shown that aging can be deliberately slowed. The authors highlight several striking findings:

-
**Restricting calorie intake** in mice, or introducing mutations in nutrient-sensing pathways, can extend lifespans by as much as **50%**.
- These so-called "Methuselah mice" are more likely than control mice to die *without* any apparent disease.
- Post-mortem examinations reveal that tumors, heart problems, neurodegeneration, and metabolic disease are generally reduced or delayed in long-lived mice.

In other words, extending lifespan in animals also appears to increase healthspan. The diseases of old age are not randomly scattered — they seem to share an underlying engine, and slowing that engine slows everything at once.

Dr. Seals and Dr. Melov add that genetic and pharmacological manipulations can increase life span in worms, flies, and rodents, with some evidence that these manipulations also increase *healthy* lifespan. A key study cited in this context is the 2009 work by Harrison and colleagues in *Nature*, which showed that the drug rapamycin extended lifespan in mice.

## Why Aging Is Malleable: Evidence from Humans

The million-dollar question: do these animal findings apply to people? The authors say the evidence strongly suggests yes.

**First, the biology is shared.** Longevity pathways identified in model organisms "seem to be conserved in humans and can be manipulated in similar ways." Genetic surveys of centenarians point to hormonal and metabolic systems as key players in extreme longevity, consistent with what animal studies predict (Barzilai and colleagues, 2010).

**Second, long-term calorie restriction in humans** produces "drastic metabolic and molecular changes" — particularly in inflammatory and nutrient-sensing pathways — that make people resemble younger individuals. Mice engineered to have reduced signaling in these pathways live longer; humans with similar mutations have lower rates of cancer and diabetes. One striking example comes from a 2011 study by Guevara-Aguirre and colleagues, who studied people with growth hormone receptor mutations and found them largely protected from cancer and diabetes.

**Third, real-world examples abound.** The commentary includes a photo of Fauja Singh, who at age 100 was preparing for Britain's Edinburgh Marathon in 2011. It also notes that groups practising strict healthy lifestyles — such as the Seventh-day Adventists, many of whom follow a mostly vegetarian diet — "frequently enjoy good health until near the end of life."

The conclusion is direct and hopeful: **"The rate of ageing, it seems, is malleable, not fixed."**

## Drugs and Diets on the Horizon

Several molecular pathways that increase longevity in animals are already affected by approved and experimental drugs. The authors walk through the most promising candidates:

-
**Rapamycin** — a drug already used to treat cancer and prevent organ rejection. It extends lifespan in mice and worms by muting the **mTOR pathway**, which regulates everything from protein synthesis to cell proliferation and survival.
-
**Sirtuin activators** — the sirtuin proteins, involved in a wide range of cellular processes, are activated by naturally occurring compounds such as **resveratrol** (found in red wine). These compounds extend lifespan in metabolically abnormal obese mice.
-
**Metformin** — a common diabetes drug. It mimics changes observed in animals fed calorie- and protein-restricted diets.
-
**Fasting** — triggers cellular responses that boost stress resistance and reduce oxidative damage and inflammation. In rodents, fasting protects against diabetes, cancer, heart disease, and neurodegeneration.

The authors emphasize that "a plethora of natural and synthetic molecules affect pathways that are shared by ageing, diabetes and metabolic syndrome." In other words, the drugs we already use for metabolic diseases may have anti-aging effects waiting to be tested.

They stress, however, that these are leads — not yet proven treatments for humans. The point of their commentary is to urge that these leads be moved into rigorous clinical trials.

## The Demographic Challenge Ahead

The urgency comes from the numbers. The article includes a chart based on United Nations projections showing the global population aged over 60 climbing from roughly half a billion in 1950 to an estimated **2.5 billion by 2050** — with developing countries accounting for the majority of that growth.

Other key projections highlighted in the article:

- The number of people over age 80 will **triple globally by 2050**.
- The number of people aged over 60 in 2050 is projected to be **five times** what it was in 1950.

The authors warn that without interventions to slow aging, this demographic shift could result in "a demographic crisis of increased disability and escalating health-care costs." Every year of additional healthspan, they argue, would relieve pressure on both individuals and health systems.

## A Major Roadblock: Funding and Focus

So why haven't these insights transformed medicine already? The authors are blunt: scientists are not set up to capitalize on these leads.

The numbers tell the story. The Division of Aging Biology at the US National Institute on Aging receives **less than 1% of the National Institutes of Health's (NIH) budget** — even though it supports research into the mechanisms underlying most disabilities and chronic diseases. Most grants focus on diseases of specific systems (such as Alzheimer's), and most study sections are not designed to evaluate multidisciplinary research on healthspan. The situation is similar in Europe and Japan.

There are also communication gaps:

- Clinicians do not realize how much is understood about the molecular mechanisms of aging and its broad effects on disease.
- Laboratory researchers are naive about the clinical implications of side effects or overdoses.
- Researchers of all stripes focus too much on easing or reversing the progression of diseases — rather than preventing them by targeting aging.

The authors also point to a deeper structural problem: **economic incentives in both biomedical research and health care reward treating diseases more than promoting health.** They note the launch of a few anti-aging biotech companies, such as Calico (created in 2013 by Google), as promising — but insist that public money must be invested in extending healthy lifespan by slowing aging. "Otherwise," they warn, "we will founder in a demographic crisis."

One more provocative suggestion: gerontologists should work with people who are middle-aged or even younger, not just the elderly — because the best time to slow aging may be decades before diseases appear.

## How We Measure Aging: The Power of Simple Tests

Before we can test anti-aging treatments, we need to measure aging itself. Dr. Seals and Dr. Melov explain that gerontologists and geriatricians have developed batteries of tests to assess declines in physiological function as people age. These tests are simple but remarkably predictive:

- The ability of insulin to clear glucose from the blood tracks the risk of diabetes.
- Stiffer arteries indicate a future of hypertension and cognitive impairments.
- Reduced bone density increases the risk of fracture.

Perhaps most striking: **life expectancy and the likelihood of disability for people over 65 can be predicted from reductions in grip strength, average walking speed, or the ability to sit and rise from the floor.** These findings come from studies such as the 2011 *JAMA* paper by Studenski and colleagues, which showed that gait speed predicts survival in older adults.

Regulatory authorities in the United States and the European Union are already considering using combinations of these physical-performance tests to evaluate the effectiveness of drugs in clinical trials for age-related disorders — including sarcopenia (the muscle-wasting condition that affects many older adults).

In other words: your doctor's simple questions about how fast you walk and how easily you get up from a chair are not trivial. They are validated measures of biological aging.

## The Gap: What's Missing in Animal Studies

Here's the problem: while human researchers have these functional tests, animal researchers mostly do not. In 2004, the US National Institute on Aging launched a programme to test strategies that extend lifespan in mammals. Multiple facilities are funded to assess the same parameters in several mouse strains under standardized conditions. But the authors note a glaring flaw: **most measurements occur only after the animals die.**

Few studies track declines in living animals — thinning bones, hearts pumping less efficiently, or sluggishness in cognitive tasks. The first thorough paper on evaluating cardiovascular function in ageing mice was published barely five years before this commentary (Dai and colleagues, *Circulation*, 2009).

This matters because animals have "physiological redundancies" — manipulating a gene or signaling pathway does not necessarily change the function of an organ or organism. A drug that slows aging should slow declines in several organ systems, but few laboratories can measure this in animals.

Even when animal studies do assess function, the conditions often have little relevance to human aging:

- Experiments on whether a drug improves cardiac function typically use **young mice** whose hearts have been purposely injured — rather than old mice with naturally aged hearts.
- To study obesity, mice are fed diets of up to **70% fat**, with high proportions of trans and saturated fats — diets that bear little resemblance to typical human diets.
- Effects of inflammation are induced with molecules like **lipopolysaccharide** at concentrations that would never be observed in normal physiology.
- Damage from oxidative stress — which accumulates over years in humans — is rapidly induced with toxic chemicals such as **paraquat**.

Each of these models has its place in science, the authors say, but they are poor mimics of human aging. Translational studies — studies designed to bridge animal and human research — must be different.

## Building Better Tools to Track Aging

What would better animal research look like? The authors offer specific suggestions.

**First, track the same animals as they age.** Researchers need new methods to characterize function — particularly to follow mice before and after interventions, using imaging tools and minimally invasive techniques. They should measure parameters such as blood pressure, metabolic rate, cardiac output, and kidney filtration — both at the animals' normal resting state and in response to common physiological challenges, such as running on an exercise wheel or completing a maze.

**Second, prioritize motor and cognitive functions.** These are the assessments most likely to be recognized by drug regulators and industry. As in human studies, function should be characterized in several organs and tissues, not just one.

**Third, account for variability.** Variability among animals increases with ageing, and study designs must accommodate that.

**Fourth, build more specialized laboratories.** One model facility is the Healthspan Assessment Laboratory at the Mayo Clinic in Rochester, Minnesota. It quantifies muscle strength and cognitive impairment, and can measure body composition, metabolic rate, insulin sensitivity, motor coordination, bone density, and exercise capacity. The Buck Institute for Research on Aging in Novato, California — where Dr. Melov works — has established similar resources. The authors say more facilities like these are needed.

The NIH has already released a set of testing batteries for clinical research — including tests for balance, memory, strength, and perception — designed to make it easier to combine results from different trials. Longitudinal human studies such as the NIH-supported **Health, Aging, and Body Composition (Health ABC) Study** have collected body scans, health inventories, and physical performance data (such as walking speed) that establish clinically relevant measures of bone density, blood pressure, and motor function.

The key idea: these same kinds of assessments, adapted for rodents, should be used to determine which of the **hundreds of pharmacological compounds and nutritional interventions** shown to slow the effects of aging in model organisms deserve to advance to human trials.

## Recommendations: A Roadmap Forward

The authors close their essays with a concrete roadmap for accelerating the science of healthy aging.

Dr. Fontana's team recommends:

1.
**Design animal studies to better mimic human aging.** For example, frailty indices are often used in human studies — comparable indices should be developed for mice.
1.
**Develop suitable endpoints for human trials.** Animal work suggests many candidate biomarkers, such as accumulation of molecular damage to DNA, proteins, and lipids from oxidative stress.
1.
**Collect biological samples during existing clinical trials.** Publicly funded trials — such as one studying whether aspirin can prevent heart attacks and general decline in the elderly — could also collect crucial samples of blood, muscle, and fat for molecular analysis.
1.
**Create translational committees.** Funding agencies should establish committees of translational scientists to review which markers of biological aging are most consistent between animals and humans, and prioritize the most practical for further assessment.
1.
**Evaluate biomarkers across a broad age range.** Chosen biomarkers should be assessed in clinical studies of patients already being treated with drugs that increase lifespan in animal models. Assessments must also be developed for dietary or other non-drug interventions.
1.
**Change the mindset.** The most important change is cultural: reward preventing disease and promoting health, not just treating sickness.

Dr. Seals and Dr. Melov add:

1.
**Expand functional assessments in model organisms** — especially rodents — using tests already established in humans.
1.
**Require basic and clinical researchers to collaborate more.** At the NIH, basic and clinical research relating to the biology of aging are administered in separate programmes — a structural barrier to translation.
1.
**Rethink training and funding.** The entire ageing-research community must rethink how its members communicate, interact, are trained, and are funded.

The authors acknowledge that the need for this kind of "crosstalk" in aging research has been stated frequently before — "with little effect." But they believe the development of standardized functional assessments that extend from model organisms to human populations may finally make it happen.

## What This Means for Patients Today

It's important to be clear about what this commentary does — and does not — say for patients right now.

**What it does say:** The current tools for extending healthy life — better diets and regular exercise — are effective. But there is room for improvement, especially in personalizing treatments. The evidence that healthy lifestyle habits matter is strong: the Seventh-day Adventists and other groups who maintain strict healthy lifestyles "frequently enjoy good health until near the end of life."

**What it does not say:** The article does *not* recommend that patients start taking rapamycin, metformin, or resveratrol to slow aging. These are research leads, not proven treatments. The authors explicitly call for rigorous clinical trials to determine which interventions work in humans — and at what doses, in which people, and with what side effects.

There is also a strong emphasis on prevention starting earlier in life. The authors suggest gerontologists should work with people who are middle-aged or even younger — because aging is a lifelong process, and waiting until diseases appear may be waiting too long.

For older adults, the practical takeaways are straightforward:

- Your functional abilities — grip strength, walking speed, balance — are meaningful measures of health, and they can be improved with exercise.
- Diet matters at every age; calorie restriction and fasting are active areas of research, but should only be undertaken with medical supervision.
- Participating in clinical research, when appropriate, can help accelerate the discovery of anti-aging therapies.

## Limitations and Open Questions

This article is a commentary — an expert perspective — rather than a new clinical study. As such, it has important limitations.

The animal findings, while impressive and consistent, have not yet been translated into proven human therapies. The 50% lifespan extension seen in calorie-restricted mice does not necessarily translate to the same magnitude of effect in humans, who live much longer and have far more complex biology. The evidence that drugs like rapamycin extend lifespan in animals is strong, but long-term safety and effectiveness data in humans are lacking.

The biomarkers the authors propose — such as molecular damage from oxidative stress — are promising candidates, not validated endpoints. The field has not yet agreed on what constitutes a meaningful "anti-aging" outcome that regulators would accept.

Furthermore, the article was published in 2014. Some of the funding figures and institutional structures described may have changed since then. The field of geroscience has grown considerably, and some of the recommendations (such as standardized functional assessments in animals) have been partially adopted. However, the core argument — that we should target aging itself rather than individual diseases — remains highly relevant and actively debated.

Finally, the authors themselves note that many unanswered questions remain: Which pathways are most important in humans? What are the side effects of long-term interventions? How do we personalize anti-aging treatments? These questions can only be answered through the clinical trials they advocate.

## Frequently Asked Questions

### Can we slow down aging? What does the research say?

Studies in animals, human genetics, and very long-lived people suggest aging is not fixed and can be slowed. However, these are research findings, not yet proven treatments. Scientists are calling for rigorous clinical trials to test anti-aging interventions in humans, but no drug is currently recommended for slowing aging.

### What is healthspan and why does it matter?

Healthspan is the number of years lived without chronic age-related disease, such as cancer, heart disease, or diabetes. Researchers argue that extending lifespan is only worthwhile if it also extends healthspan. Current medicine treats diseases one at a time, but aging itself is a common risk factor for many conditions.

### How can I measure my biological age or aging?

Simple functional tests are surprisingly predictive. Grip strength, walking speed, and the ability to sit and rise from the floor can predict disability and survival in people over 65. Stiffer arteries and reduced bone density also indicate aging. These measures are used in research and can be improved with exercise.

### What lifestyle habits are effective for healthy aging?

Better diets and regular exercise are effective, according to the article. Groups like Seventh-day Adventists, who follow strict healthy lifestyles with mostly vegetarian diets, frequently enjoy good health until near the end of life. Calorie restriction and fasting are active research areas but should only be done with medical supervision.

### Why is treating diseases one at a time failing older adults?

Because aging comes as a package: over 70% of people over 65 have two or more chronic conditions at once. Treating heart failure, cancer, and diabetes separately ignores that aging is the common risk factor. Delaying one age-related disease probably staves off others, so targeting aging itself may be more effective.

### What should patients do today based on this research?

There are no proven anti-aging medications yet. Focus on healthy diet and exercise, since functional abilities like walking speed and grip strength are meaningful and can improve. Consider participating in clinical research if appropriate. The article does not recommend taking rapamycin, metformin, or resveratrol for aging.

### Should I get a second opinion before taking anti-aging drugs like rapamycin or metformin?

The article emphasizes that rapamycin, metformin, and resveratrol are research leads, not proven treatments, and it does not recommend that patients start taking them to slow aging. The authors call for rigorous clinical trials to determine which interventions work in humans, at what doses, and with what side effects. A second opinion can help you weigh whether a proposed anti-aging treatment is supported by evidence or still experimental, and whether lifestyle measures like diet and exercise are more appropriate. Diagnostic Detectives Network provides independent expert second opinions.

## Source Information

This patient-friendly article is based on peer-reviewed research published as a two-part Commentary in *Nature* (Volume 511, pages 405–407, 24 July 2014).

**Original article title:** tactics to stamp out herbicide

**Authors:**

- Luigi Fontana, MD, PhD — Professor of Medicine and Nutrition, Washington University in St. Louis, Missouri, USA, and Brescia University, Italy.
- Brian K. Kennedy, PhD — Director, Buck Institute for Research on Aging, Novato, California, USA.
- Valter D. Longo, PhD — Director, Longevity Institute, University of Southern California, Los Angeles, USA.
- Douglas Seals, PhD — Professor, Department of Integrative Physiology, University of Colorado Boulder, Colorado, USA.
- Simon Melov, PhD — Director of Genomics, Buck Institute for Research on Aging, Novato, California, USA.

**Note:** This patient-friendly article is based on the original commentary published by Macmillan Publishers Limited. Key studies referenced in the original include Fontana, Partridge & Longo (*Science*, 2010), Harrison et al. (*Nature*, 2009), Studenski et al. (*JAMA*, 2011), Guevara-Aguirre et al. (*Science Translational Medicine*, 2011), and Longo & Mattson (*Cell Metabolism*, 2014). This translation is provided for educational purposes and does not constitute medical advice. Always consult a qualified healthcare provider before making changes to your diet, medications, or exercise routine.


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