Can Human Aging Be Reversed?

Although the study of human aging is relatively nascent and still developing, it holds promise for helping people live longer, healthier lives. Preliminary data support this optimism and argue that clocks that measure biological aging—the gradual deterioration of characteristics at the level of molecules, cells, tissues, and behaviors—are sensitive to health-promoting interventions in humans. But the question that everyone seems to want an answer to is: Can human aging be reversed?  

In a recent publication, scientists from Longevity Sciences, Inc. and Harvard Medical School examined the relationship between certain chemicals and the slowing down or reversal of expected biological age. The authors point to existing evidence suggesting that human aging clocks are adjustable. Comprehensive clinical trials are required to confirm these preliminary findings, and the clinical significance of slowing or reversing an aging clock will need to be elucidated.

What is biological aging?

Biological aging is an abstract yet intuitive concept that helps explain why different individuals exhibit diverse aging trajectories. People of equivalent chronological age are not necessarily the same biological age. And although chronological age correlates with various age-related diseases and conditions, it does not adequately reflect an individual's functional capacity, well-being, or mortality risk. In contrast, biological age provides information about overall health and indicates how rapidly or slowly a person is aging.

The history of aging clocks

In 1974, Dr. Werner Ries wrote that the ability to predict biological age accurately would be of significant importance for geriatrics. A useful predictor would be quantitative, non-invasive, and reflect human functional capacity. Over the next several decades, multiple attempts were made to quantify this elusive metric. For example, 24 age-related variables were transformed into biological aging scores by Borkan and Norris in 1980. Physicians estimated that individuals with a higher biological aging score looked older and had a higher risk of mortality. Subsequent age predictors were created using physiological variables, fitness test results, visual estimation, frailty index scores, physical and biochemical parameters, and answers to the work ability index.

Now, estimates of biological age are provided by aging clocks, which are computational models that use a set of inputs to make a prediction. Aging researchers have created aging clocks using several types of modifications throughout the genome. Overall, a considerable amount of research in the field of biohorology—the science of measuring the passage of time in living systems—has shown that specific diseases and factors are linked to age acceleration. In the past decade, aging clock studies have shown that several age-related and mental health conditions as well as social variables associate with an increase in predicted biological age relative to chronological age. This phenomenon of age acceleration is linked to a higher risk of premature mortality.

Aging clocks are helpful research tools, but they also can help people make decisions and offer personal proof that a particular change is related to slower or quicker aging. Although biohorology is still a young and emerging profession, it has the potential to help individuals live longer, healthier lives. This optimism is supported by preliminary studies, which claim that aging clocks in people are responsive to therapies that improve their health. Yet, few aging clock studies have connected a particular intervention or variable to a decreased biological age. Future studies are necessary to fully comprehend the connection between these computational models, lifespan, and health to clarify the therapeutic importance of slowing or reversing the aging clock. 

Is there scientific evidence for biological aging reversal?

A multitude of factors has been shown to associate with human age deceleration. In fact, it’s not surprising that a person's aging trajectory may be reversed by making a health-promoting shift, such as switching to a healthier diet and engaging in more leisurely physical activity.

A study performed by Quach and colleagues identified several variables significantly correlated with slower aging of the epigenome—patterns of DNA modifications that influence gene activity programs. These factors include fish intake, fruit and vegetable consumption, physical activity, education, and income. Subsequent work by Levine and colleagues constructed a new clock corroborating that education, income, exercise, and consumption of fruit and vegetables are linked with a lower epigenetic age.

Other groups have likewise connected dietary factors, physical activity, and other lifestyle choices to a slower aging clock. Interesting examples to highlight include supplementation with omega-3 and vitamin D as well as adhering to a Mediterranean diet. A recent study by Demidenko and colleagues showed that the epigenetic age of 42 subjects taking a supplement containing 1000 mg of calcium alpha-ketoglutarate for an average period of 7 months was reduced by 8 years post-supplementation. Although this trial was small and lacked a control group taking a placebo instead of calcium alpha-ketoglutarate, the findings are interesting given that calcium alpha-ketoglutarate extends lifespan and improves health in mice.

Clinical trials in humans have shown that caloric restriction supports healthy weight, sleep, and the immune system. What’s more, there is research that has shown the reversal of biological clocks. Reprogramming—the activation of essential proteins crucial for stem cells to remain youthful—has been shown to reverse the aging clock in mice and cultured human cells. Additionally, epigenetic aging is reversible in response to various therapies.

What’s next for human biological aging reversal?

Although fascinating, these results need to be interpreted with caution. It is controversial if the statistic offered by an aging clock accurately indicates biology. These clocks ultimately do a computation based on a variety of inputs, most of which are molecular in origin and predictably change with population age. The need for more studies to clarify the connection between biological aging and aging clocks cannot be overstated.

Future studies utilizing aging clocks must be cautious to use conventional clinical metrics. In the end, it is debatable if it is useful for biological aging to slow down if there aren't concurrent functional gains or lowered mortality risks. On the other hand, a slowing of biological aging that is associated with a definite improvement in health and/or a longer life is of interest. Long-term, longitudinal studies in older populations would be highly beneficial and provide an understanding of how a change in biological aging affects mortality risk on a personal level. We will have a better knowledge of how clinically meaningful changing the aging clock is when additional studies are released.