Understanding Aging: The Biological Perspective on Growing Old

It's a misconception to label someone as old simply based on their age or health conditions.

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Who exactly qualifies as an elderly person? Is it anyone over 50? Or those suffering from age-related ailments? Polina Loseva, a biologist and science writer, argues that the answer is far from straightforward. Together with Alpina Non-Fiction Publishing, we share an excerpt from her book "Against the Clock: What Aging Is and How to Fight It," specifically the chapter titled "In Search of a Definition: Who Is Truly Old?"

Drawing the Line

Initially, one might define 'old' as someone who has lived many years. But how many years count as 'many'? Is 30 considered old? 40? 60? Setting a universal age threshold to define old age is tempting, such as retirement age. However, retirement ages vary globally and are frequently adjusted to match increasing life expectancies—for example, Romania raises it by one year every four years, Belgium every five. This variability complicates deciding when and how to adjust the boundary of old age. Hence, relying solely on age is insufficient; other non-age-related markers are necessary.

Another challenge with age thresholds is that they simplify aging to a single moment—turning 60, for example, instantly makes someone old. While this works in stories, aging is actually a gradual process spanning years.

Viewing aging as a developmental process suggests it should be continuous rather than abrupt.

Moreover, how do we apply this to animals? If anti-aging treatments are tested on model organisms before humans, the aging criteria must apply across species with vastly different lifespans—from days to centuries—and varying lab versus wild lifespans. This requires either species-specific thresholds or a universal biological marker applicable to all organisms.

Judging by Appearance

Since age is an unreliable marker, external signs like gray hair, stooped posture, wrinkled skin, unsteady gait, or memory loss might be used to identify old age. Yet, exceptions abound: some young individuals gray early or bald prematurely; posture problems affect many office workers; sun-exposed villagers may have wrinkled skin regardless of age.

Thus, relying on physical traits risks misclassifying people of various ages and conditions, including disabilities or mental illnesses. Wealthier individuals who can afford skincare often appear younger than less affluent peers.

This approach is flawed because these signs don't directly reflect the biological mechanisms of aging. They represent outcomes, like judging porridge readiness by spilled milk—careful handling might cook the porridge perfectly, whereas high heat could cause a mess early on. To truly grasp aging, we must look inside the 'pot'—investigating the causes and earliest signs.

Testing in Practice

According to Wikipedia, "Old age is the period from the loss of reproductive ability until death." This definition ties aging to internal biological changes and is measurable by an organism's ability to reproduce.

However, this reproductive criterion is impractical for humans. Many do not continuously reproduce, and reproductive potential varies: women’s healthy eggs typically diminish by ages 40–45, though modern reproductive technologies enable childbirth into the 50s and even 60s, with the Guinness World Record near 67 years. Men produce sperm continuously until death, complicating comparisons. External aging signs like wrinkles appear similarly in men and women, yet women generally live longer.

Therefore, reproductive capacity is as unreliable as appearance for defining old age. Many 40- and 50-year-old women look young but often choose not to have children, and cosmetic interventions can preserve youthful looks even into the 70s.

Counting Mutations

When asked what aging is, many say it's the accumulation of damage and malfunctions. Reproductive decline fits this but varies individually, making it an unreliable universal marker.

Medical researchers use "frailty indices"—collections of symptoms and age-related diseases—to estimate biological age. Higher indices indicate proximity to old age. Yet this too reflects outcomes rather than causes, and wealthier individuals often score lower, appearing biologically younger.

Ultimately, we must delve deeper—into cells and molecules—to identify aging signs at the microscopic level.

One molecular hallmark is point mutations in DNA—single-letter changes in the genetic code. Most are harmless due to genetic redundancy, but mutations in critical genes can disrupt protein function, potentially leading to diseases like cancer.

While assessing the impact of each mutation is complex, treating every point mutation as damage offers a practical approach. This means DNA begins accumulating aging signs from conception.

In 2018, two research teams analyzed point mutations in human nerve cells from embryos and adults. Ideally, all cells share identical DNA sequences, but mutations accumulate independently. Comparing neighboring cells reveals mutation counts.

Findings are striking: during early embryonic cell divisions, about 1.3 new mutations occur daily. By the 15th week of development, mutation rates increase to about five per day. By the 21st week, nerve cells harbor around 300 unique mutations. At birth, dividing cells have up to 1,000 mutations. Throughout life, mutations accumulate more slowly—about 0.1 per day—resulting in approximately 1,500 mutations by age 45 and 2,500 by age 80.

If each mutation counts as damage, aging begins right after fertilization, challenging our intuition about aging as deterioration of fully formed structures.

At the molecular level, aging is a continuous process starting from the earliest development stages.

Mutations accumulate steadily, making it difficult to define a clear boundary between youth and old age. Setting a mutation threshold faces the same challenges as retirement age: it requires additional markers like appearance or reproductive capacity, which are unreliable.

Considering mutation rates instead of counts also complicates matters, as embryonic nerve cells mutate faster than adult ones. Dividing cells in adult organs like the intestine and liver mutate at similar rates to nerve cells, so mutation metrics don’t simplify aging definitions.

Diagnosing Aging

Clearly, aging and defining who is old lack a sharp starting point. Aging is a gradual process with an end but no clear beginning. Nonetheless, physicians identify aging through age-related diseases and treat symptoms where possible—replacing teeth, fitting hearing aids, managing heart conditions, or corneal transplants. From a medical standpoint, old age is a collection of commonly treatable defects.

This clinical approach is currently our most effective life-extending strategy.

Regardless of underlying aging mechanisms, medicine has significantly improved longevity by combating direct causes of death. Infectious diseases no longer cause mass fatalities in developed countries, paralysis is no longer a death sentence, and conditions like hypertension and diabetes are manageable with medications. Over the past century, average life expectancy has nearly doubled. The fight against aging is well underway despite lacking a clear enemy definition.

However, truly defeating aging likely requires preventing age-related diseases before they arise. Thus, any future "anti-aging pill" would need to be taken preemptively to combat a disease not yet present. Currently, the International Classification of Diseases lists "old age" as a cluster of symptoms like frailty and asthenia but does not classify aging itself as a disease.

This status quo has drawbacks: it hampers research, as gerontologists cannot conduct clinical trials for anti-aging drugs without a recognized disease target. Trials often focus on age-related diseases like arthritis; improvements in these conditions may incidentally extend lifespan.

Conversely, classifying aging as a disease implies a large portion of humanity is chronically ill and incurable, which conflicts with medical definitions of disease as deviations from health. If aging is measured by mutations, everyone is affected.

Currently, gerontologists advocate for recognizing aging as a disease, while many clinicians resist. However, with biohackers self-experimenting and private trials emerging, medical consensus may eventually shift to acknowledge aging as a disease and establish unified definitions.

Polina Loseva is a biologist with a degree in embryology from Moscow State University's Faculty of Biology. She writes for popular science platforms such as Cherdak, N+1, Elements, and OLYA, promoting scientific literacy. In "Against the Clock," she explores aging mechanisms, efforts to develop anti-aging treatments, and strategies to delay the inevitable.

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