Taking it Slow: How Faster ‘Paces of Aging’ Accelerate Biological Clocks and Age-Related Disease

With the global population of people aged 80 years or older expected to triple by the year 2050, the societal and financial burden of age-related disease and disability will likely rise simultaneously. From the heart to the kidneys to the brain, increasing age is almost always associated with a functional decline of many, if not all, organ systems. But, at what age is this decline most likely to start occurring? Although longevity and anti-aging research has exploded in recent years, most of these human studies are carried out in older adults. While still illuminating, research in older adults fails to fully capture the beginning of subclinical organ dysfunction that may start in early-to-mid-life — and, with that, fails to prevent it from occurring in the first place. 

Rather than treating each organ’s decline separately once they have succumbed to disease, researchers now wonder if it’s possible to prevent all of these age-related chronic diseases by targeting aging itself. Known as the ‘Geroscience Hypothesis,’ this theory suggests that increased biological age — the internal measure of damage and dysfunction to cellular markers that can deviate from the age on your birth certificate — drives the typical onset of age-related chronic diseases. Instead of treating kidney disease separately from heart failure in later life, for example, the Geroscience Hypothesis posits that slowing down whole-body biological aging in early-to-mid-life should be a primary target to prevent or delay these organ-specific diseases before they even begin.

In a recent study published in Nature Aging, Elliott and colleagues followed a cohort of 1,037 people in New Zealand from birth to age 45 to assess the disparities in biological age among adults with the same chronological age. Referred to as the Pace of Aging, the research team compiled 19 biomarkers across the cardiovascular, metabolic, renal, immune, dental, and pulmonary systems at ages 26, 32, 38, and 45 to create one composite score of biological age. After measuring health outcomes across four domains — brain aging, cognitive decline, sensory-motor function, and external appearance —  the research team was better able to understand how a faster Pace of Aging in mid-life correlates with the subclinical changes in organ function that contribute to disease development in later life. 

The Decline and Dysfunction of the Middle-Aged Brain

Since the brain is one of the most common organs to decline with age, brain function and cognition were of primary focus to the researchers. Various imaging techniques can detect brain aging decades before the onset of dementia, which was verified in this study. In this cohort of 45-year-olds, those with a more accelerated Pace of Aging showed significant changes to brain function and structure. These changes included a smaller hippocampus size — the area of the brain related to learning and memory — and a thinner cerebral cortex, a region involved heavily with speech, thinking, and memory. Additionally, greater biological age was linked to the deterioration of white matter, the brain tissue that contains high amounts of axons, or the threadlike projections of nerve cells that facilitate signaling to other neurons 

With these structural changes came a decline in cognitive function. Despite being decades away from a potential dementia diagnosis, people with faster Paces of Aging had lower IQs and poorer scores on numerous cognitive tests measuring memory, processing speed, learning abilities, and comprehension skills. In addition to these quantitative measures, these differences were noticeable in their day-to-day lives, as those with higher biological ages were more likely to have forgetfulness, lack of focus or attention span, and general memory difficulties. 

Overall, the average “brain ages” of people with a faster Pace of Aging score were 3.8 years older than people with the slowest accruement of biological age. Despite the average age of Alzheimer’s disease diagnosis being 80 years old, many of these 45-year-olds with accelerated biological aging exhibited similar signs and symptoms. While this indicates that increased Pace of Aging is a significant measure of brain health and cognition at age 45, we don’t yet know if mid-life biological age is an entirely malleable marker — meaning, are our mid-forties too late to slow down this ticking internal clock? Elliott and colleagues don’t necessarily think so, stating that “Interventions that can achieve even mild slowing of biological aging promise to improve quality of life in older adults while yielding substantial healthcare savings.” 

Aging, From the Inside Out

Next, Elliott and colleagues measured how well the participants performed on various tests related to sensory and motor function. People with faster Paces of Aging showed significant signs of motor decline, including slow gait speed, poor balance, slower stepping-in-place scores, weaker grip strengths, and worsening fine motor control — all factors that increase the risk of falls, fractures, frailty, and loss of independence with age. Similarly, people with greater biological ages exhibited diminished sensory abilities, including visual and hearing decline. Lastly, the fourth domain looked at external appearances and perceptions of aging. Those with higher Paces of Aging had more negative attitudes about growing older, including feeling older than their age or not feeling healthy. Externally, they were more likely to be reported by their peers as looking older than their chronological ages. 

Will Biological Clocks Be the New Birthdate? 

This study adds to the evidence that chronological age is a substandard proxy for biological age, as seen by this cohort of 45-year-olds who varied widely in their Pace of Aging and related health biomarkers. Previous research from the same team showed that accelerated internal aging was even seen two decades earlier, as adults in this cohort with faster Paces of Aging exhibited brain aging and physical decline as early as age 26. 

This led Elliott and colleagues to wonder if biological age should be used to determine whether the eligibility age of receiving ‘older adult’ social support should change. From Medicare to Social Security to pension plans, all of our society’s programs for older adults begin in the sixth decade of life to support financial- and health-related independence with age. But, these birthday-based enrollment dates fail to take into account internal health, as the differences between a healthy and vibrant 85-year-old and a disease-ridden 65-year-old are vast. As an alternative to these chronologically-aged start dates, Elliott and colleagues suggest a new method for entering these social programs: biological age, or Pace of Aging.

As the average lifespan is getting longer, the economic burden of enrolling healthy 60-65-year-olds in these programs may soon be too great to handle. Instead, this research team suggests that the future of social program eligibility and allocation should lie in markers of biological age. This would also allow younger adults, for example, to receive Medicare benefits if their biological age — and likely accumulation of chronic diseases — was greater than age 65. However, this method is likely to be far off, as the ability to measure these internal markers is not readily available for all. As summarized by the authors, “Perhaps someday we will be able to use biological aging measures to guide treatment access. With further development, geroscience could provide the conceptual tools, measurement technology, and interventions required to mitigate disparities in the pace of biological aging through more tailored and just access to independence-sustaining resources.”

References: 

Belsky DW, Caspi A, Houts R, et al. Quantification of biological aging in young adults. Proc Natl Acad Sci U S A. 2015;112(30): E4104-E4110. doi:10.1073/pnas.1506264112

Elliott ML, Caspi A, Houts RM. et al. Disparities in the pace of biological aging among midlife adults of the same chronological age have implications for future frailty risk and policy. Nat Aging. 2021;1:295–308. https://doi:10.1038/s43587-021-00044-4