Is aging actually a disease?

People all over the world are living longer, with life expectancy dramatically increasing in the past 150 years. Between 2020 and 2050, the world’s population aged 60 years and older is expected to double, increasing from 1 billion to 2.1 billion. 

While there has been an increase in life expectancy, the years gained are not all healthy—with the proportion of years spent in good health remaining roughly constant. This suggests that people are living longer, but in poor health. Accompanying this shift in the age distribution of the world’s population has been increasing emphasis on the concept of healthy aging. This has led to debates on the best way to classify the process of aging. 

Defining aging 

At the biological level, aging is the result of a gradual accumulation of molecular and cellular damage over a person’s lifespan. These changes at the molecular level lead to a decline in mental and physical function and a heightened risk of disease—ultimately leading to death. 

Aging has been defined as a natural and universal process, and therefore, was not seen traditionally as a disease. Advocates of classifying aging as a natural phenomenon have argued that aging is not a deviation from the normal state, as would be expected for a disease. 

While the classification of aging as a disease remains a hotly contested topic, more researchers are starting to view aging as an actual disease state and not just an advancement of age that increases the risk for other ailments. To highlight this shifting consensus, the WHO has formally recognized aging as a disease in its latest version of the International Classification of Diseases (ICD-11). 

Benefits of classifying aging as a disease 

The formal recognition of aging as a disease paves the way for the development of therapeutic interventions and strategies that target aging and aging-related diseases. This recognition is also critical to increasing funding from grant-awarding organizations for aging research. Once therapeutic interventions for aging exist, the acceptance of aging as a disease will also be imperative to ensuring that treatments are covered by health insurance providers. 

Economic value

In a 2021 article published in Nature Aging, investigators found that targeting aging—instead of other diseases associated with it—could have a substantial, positive impact on the economy. 

Using the value of statistical life (VSL) methodology, an algorithm commonly used by government agencies to enact policy measures and treatments, the study’s authors put a value on the potential monetary gains from an increase in life expectancy, better health, and changes to the rate of aging. They found that slowing down aging by increasing life expectancy by 1 year was worth $38 trillion. Increasing life expectancy by 10 years led to a gain of $367 trillion, highlighting the economic value of improving how people age.

The study also explored the benefit of using Metformin, a type 2 diabetes drug that has been shown to protect against age-related diseases, as a hypothetical intervention for aging. In the simulation, metformin use was predicted to lead to significant benefits, matching or surpassing those gained from the complete elimination of cancer, dementia, or cardiovascular diseases. This work highlights the potential benefit of repurposing currently available treatments as interventions for aging.

Metformin 

Metformin has been approved to treat diabetes in the US since 1995. The anti-aging properties of metformin were first described in the model organism, C. elegans, as well as in laboratory mice. These early studies showed that the diabetes drug prolonged the lifespan of these organisms. Intriguingly, investigators also reported benefits to the animal’s healthspan, the period of life where the animals are active, suggesting that metformin promotes healthy aging. 

In humans, observational studies have suggested that diabetic patients taking metformin had a survival benefit, even compared with non-diabetic control subjects, supporting a role for metformin in delaying aging and spurring intense interest in investigating its potential to target aging. 

To build on the animal studies and observational studies in humans, a double-bind, placebo-controlled multicenter study is underway to investigate whether metformin can be used as an effective anti-aging drug in non-diabetic individuals. The Targeting Aging with Metformin (TAME) study consists of 3,000 participants, aged 65-79, who will take 1,500 mg of metformin daily for 6 years.

Despite the need for randomized clinical trials on aging in humans, some individuals have already begun metformin regimens in attempts to live longer and healthier lives. While years of data in diabetic patients have indicated that metformin is safe and well-tolerated, it is unclear if the drug will have any measurable benefits on aging in healthy individuals.  

Rapamycin 

Rapamycin is an FDA-approved drug used to prevent organ transplant rejection and treat certain cancers. Similar to metformin, rapamycin was first shown to have an effect on aging in non-human subjects, demonstrating an increase in the lifespan of laboratory mice. In humans, topical administration of rapamycin was shown to promote collagen production and decrease age spots and wrinkles. While these preliminary studies are promising, future research is needed to evaluate the efficacy and safety of using rapamycin to treat aging.

Sources

1. Blagosklonny MV. Rapamycin for longevity: opinion article. Aging. 2019;11(19):8048-8067.

2. Bulterijs S, Hull RS, Björk VCE, Roy AG. It is time to classify biological aging as a disease. Front Genet. 2015;6.

3. Fuller k. Is rapamycin the new “fountain of youth? Psychology Today. 2021. 

4. Scott AJ, Ellison M, Sinclair DA. The economic value of targeting aging. Nat Aging. 2021;1(7):616-623.

5. Soukas AA, Hao H, Wu L. Metformin as anti-aging therapy: is it for everyone? Trends in Endocrinology & Metabolism. 2019;30(10):745-755.