Is Ageing a Disease? The Door to Immortality.

The first depiction of humanity’s obsession with curing death is The Epic of Gilgamesh—which, dating back to at least 1800 B.C., is also one of the first recorded works of literature, period. Centuries later, the ancient Roman playwright Terentius declared, “Old age itself is a sickness,” and Cicero argued “we must struggle against [old age], as against a disease.” In 450 B.C., Herodotus wrote about the fountain of youth, a restorative spring that reverses aging and inspired explorers such as Ponce de León. But what once was a mythical holy grail is now seemingly within tantalizing reach. As humans’ understanding and knowledge of science and technology have increased, so too have our life spans. Until the 1800s, life expectancy across Europe averaged between 30 and 40 years, and now the average life expectancy in the U.S. is just under 79 years; in Japan and Hong Kong, it’s more than 84 years.

In 2013, a team of international researchers identified nine “hallmarks of aging”: disrupted communication between cells, genome mutations (associated with cancer), telomere shortening, changes in DNA’s chemical structure (apart from the genetic code), degradation of cellular proteins, diminished cellular ability to identify and adjust to nutrient levels, impaired mitochondrial functioning, cellular senescence (when cells stop dividing and growing due to age), and nonrenewal of stem cells. While each hallmark has symptoms, “there are no biomarkers to describe aging overall,” according to Chuck Dinerstein, senior medical fellow at the American Council on Science and Health. These hallmarks occur in every human, and because many of them occur simultaneously, it’s difficult to tease out each individual process or to identify causal relationships. We know that the net effect is aging, but there’s a lot scientists don’t yet know about the processes that causes these hallmarks. Hayflick has argued that differentiating between aging and age-associated diseases is crucial, and that the lack of distinction between them “is the most serious impediment to our understanding of the aging process.” 

Biodemographers' Point of View

Death in old age was historically attributed to just that—ie, old age and natural causes. However, with increasing life expectancy and the desire to maintain good health in older age for as long as possible (so-called healthy ageing), calls to recognise ageing as a disease that can be treated are increasingly relevant and debated, despite the lack of a universally accepted set of ageing biomarkers and uncertainty about the time of transition to disease.

Semantics and subjectivity add to the difficulty. Old age isn’t abnormal, so why would aging be pathological? If aging is a disease, then all 7.7 billion people on Earth have it, and everyone over the age of 65 has an advanced case. If you bristle at that notion, you have a sense of the designation’s damaging stigma. Suresh Rattan of Denmark’s Aarhus University’s Laboratory of Cellular Ageing believes that a condition everyone experiences can’t by definition be a disease. Yes, aging is associated with numerous health issues: heart disease, Alzheimer’s, and many types of cancer and diabetes. But while those diseases become more common as people age, not every aging person acquires them (and sometimes, younger people do). Peter Boling, director of geriatrics at Virginia Commonwealth University Medical School, noted in a panel at the 2019 Gerontological Society of America conference that such “conditions are not directly linked to aging as a biologic phenomenon per se.” In other words, while these conditions are associated with aging, they aren’t necessarily triggered by aging itself, but rather by the biological processes of aging, or the cause of those nine hallmarks. Biological processes are the cause, while age-related diseases are the effect. That means that treatments that appear to slow aging overall might actually only be addressing one symptom, and doctors and patients might not realize that limited efficacy for a long time.

Opening the door to treating ageing as a disease

Progress in being able to classify, and thus treat, ageing as a disease was made recently when WHO implemented an extension code for ‘Ageing-related’ (XT9T) diseases—defined as those “caused by pathological processes which persistently lead to the loss of organism's adaptation and progress in older ages”—in the latest version of the International Classification of Diseases, ICD-11. The new code, implemented as a result of a joint proposal submitted to WHO's ICD-11 Task Force by researchers from the Biogerontology Research Foundation, the International Longevity Alliance, and the Council for Public Health and the Problems of Demography, can be immediately applied to relevant conditions listed in ICD-11 as well as to newly recognised conditions in the future. As ICD codes are prerequisite for the registration of all new drugs and therapies, the recognition of age as a pathological process, together with replacement of the ICD-10 ‘Senility’ (R54) code with ‘Old age’ (MG2A) in ICD-11, represents undeniable progress towards overcoming the regulatory obstacles that have thus far hampered the development of therapeutic interventions and preventative strategies targeting ageing and age-related diseases.

According to WHO, 22% of the world's population (roughly 2 billion people) will be over the age of 60 years by 2050, an increase from just 12% (about 900 million) in 2015; by 2020, people aged 60 years and older will outnumber children younger than 5 years. This population ageing (a shift in the median age of a country's population towards older ages) was first evident in high-income countries such as Japan, but low-income and middle-income countries (LMICs) are now experiencing the greatest rate of change: by 2050, 80% of people older than 60 years are predicted to be residing in LMICs. Increased life expectancy can be seen as a sign of progress and prosperity in a country, reflecting improvements in health care (access, availability, and affordability), diet, work safety, and socioeconomic status together with reductions in famine, conflicts, communicable diseases, and risky health behaviours such as smoking. But the benefits of living longer are counteracted by the global rise in ill health in old age due to the increasing burden of non-communicable diseases (predominantly obesity, diabetes, cardiovascular diseases, and cancer) and ageing-related conditions. Moreover, how to provide adequate health and social care to an ageing population is a major economic challenge for all countries, threatening to cripple already overstretched health and social care budgets in some.

Although implementation of the extension code XT9T in ICD-11 is not tantamount to formal recognition of ageing as a disease, it does signal acknowledgment by WHO of ageing as a major disease risk factor and of the considerable public health problem posed by ageing-related diseases. Whether this move will be enough to entice the pharmaceutical industry to initiate development programmes targeting the ageing process and, more broadly, human lifespan remains to be seen. However, given the impending economic threat posed by population ageing and the potential benefits of intervention, ranging from better health in old age for individuals to decreased health-care costs, increased workplace productivity, and increased economic growth for countries, progress on this front is vital.

The Lancet Diabetes & Endocrinology has just published a four-paper Series on Ageing and endocrinology, highlighting endocrine-related diseases and comorbidities as some of the most common age-related conditions and major impediments to maintaining good health in old age. The papers discuss the physiological basis of endocrine-system ageing, the clinical implications of using testosterone to treat older men with hypogonadism, thyroid dysfunction during ageing, and the role of the endocrine system in frailty. Understanding how the endocrine system ages is paramount to realising the goal of healthy ageing—the door to which has at least now been opened by implementation of the ‘Ageing-related’ ICD-11 extension code.