Ageing, Alzheimer's and Immprtality: Should Scientists be Working to Increase Lifespan?

Emily Adams explores the ethics and intricaces of the ageing process, and if at all we should even be considering tampering with our natural lifespans.

Ageing is a fundamental part of the human condition that has plagued many branches of the evolutionary tree, including that of humans, since evolution began. The idea of immortality has fascinated humans for generations, from Plato’s Affinity Argument that the soul, unlike the body, is immortal, to Quantum Immortality Theory.

If asked what the biggest risk factor of disease is, many people would give an answer referring to environmental factors such as smoking. However, the answer is staring us right in the face, while slipping by seamlessly with the tick of the biological clock. Ageing, and the functional deterioration that comes with it, is the biggest risk factor for major human diseases and pathologies, from cancer, to cardiovascular disorders, to neurodegenerative diseases. Some scientists even argue that ageing should be defined as a disease itself.

The coronavirus pandemic has held a microscope up to the question of age, with the Centre for Disease Control and Prevention reporting that patients over the age of 75 are 220x more likely to die from COVID-19 when compared with 18–29 year olds.

Richard Miller, director of the Glenn Center and Professor of Pathology at the University of Michigan. Medical School, argues that: “People assume aging is immutable and that it is a fool’s errand to look for drugs that slow the aging process - but they are wrong.".

Hence, modern science is faced with a pressing question: should scientists be working to slow or prevent the process of ageing? And is this even possible in the new future?

A popular candidate for anti-ageing drug therapies was found in the soil of Easter Island in 1972: Rapamycin. Rapamycin was originally developed by Dr Surendra Sehgal as an anti-fungal drug and then later used for its immunosuppressive effects, becoming FDA approved in 1991.

More recently, rapamycin has been proposed as a potential therapy to target the second most common neurodegenerative disease, increasingly prevalent with age. Alzheimer’s disease involves a build-up of proteins called beta amyloid plaques, and it is thought that rapamycin can promote the degradation of these pathological protein plaques in the early stages of the disease by increasing the rate at which they travel to the cell’s recycling system. Clinical trials for the safety and tolerability of this drug in patients suffering from Alzheimer’s disease began in August 2021.

Rapamycin has already been used in the treatment of other diseases where a key risk factor is age, including cancer. It is currently being tested in humans and dogs for preventing heart attacks and diabetes.

However, rapamycin is now being studied for its potentially anti-ageing effects. Some question whether this compound increases lifespan due to action against age-related disease. However, evidence supports the hypothesis that rapamycin can actually slow the physiological process of ageing.

Rapamycin works by inhibiting part of the mTOR cellular pathway, which is involved in growth, autophagy (clearing out cells), and protein synthesis. Different animal models have shown that this inhibition can be associated with extending lifespan and increased longevity. In a 2016 study, administering middle-aged mice with rapamycin for just three months increased their life expectancy by up to 60%.

Yu-Xuan Lu, a postdoc in the Max Planck Institute for the Biology of Ageing, who authored a study on rapamycin and ageing in flies, says that “we use rapamycin to fine-tune the master regulator of cellular metabolism”. This cutting-edge research found mTOR inhibition by rapamycin improved gut health and increased life span in flies.

Though we are far off from preventing or even slowing ageing, the potential of anti-ageing therapies places a new power in the hands of scientists who are faced with pressing ethical questions surrounding longevity drugs.

Blagosklonny et al., 2019 warn that “not taking rapamycin may be as dangerous as smoking”, arguing that the potential years gained based on animal studies would equate to the average number of years lost in humans by smoking.

However, problems associated with increased lifespan would be exacerbated if longevity drugs are developed, for example, overpopulation and health inequality across the wealth divide. An ethical argument against increased longevity would be ennui – the concept that with no natural deadline to life, our lives lose their value.

While research should continue to develop rapamycin-based therapies for age related diseases that cause mass suffering, science must next join forces with philosophy to balance the risks and benefits of using these same drugs for direct life-extension independent of pathology. In the world of science, research and development are inevitable. It is now science’s job to consider the ethics and applications of life-extension if this wonder drug ever comes to fruition.

From SATNAV Issue 23, pages 16-17.