Three Waves Of Aging Identified

The researchers analyzed plasma from 4,263 people between the ages of 18-95, evaluating 3,000 proteins in the blood, that was narrowed to focus on 1,379 proteins that were found to vary significantly with subject age, of which 895 were generated in a profile that could predict the gender of the donor, and another 373 proteins were highly predictive of the age.

373 proteins may make one think that a lot of blood was required, but according to the researchers, a drop was all it takes for a 373 protein readout. Wyss-Coray also explained that “After nine or 10 proteins, adding more proteins to the clock improves its prediction accuracy only a bit more,” adding that, “With machine learning, you could potentially make a test with good accuracy based on just those nine proteins.”

According to the researchers they were able to predict an individual’s age within a range of 3 years, and for those whose predicted age was substantially lower than their actual age the individual turned out to be remarkably healthy for their age. Those with stronger hand grips and better measured cognition were typically estimated to be younger than they actually were. 

“Proteins are the workhorses of the body’s constituent cells, and when their relative levels undergo substantial changes, it means you’ve changed, too,” said Tony Wyss-Coray, Ph.D., professor of neurology and neurological sciences, the D. H. Chen Professor II and co-director of the Stanford Alzheimer’s Disease Research Center. “Looking at thousands of them in plasma gives you a snapshot of what’s going on throughout the body.”

The researchers noted that “By deep mining the aging plasma proteome, we identified undulating changes during the human lifespan. These changes were the result of clusters of proteins moving in distinct patterns, culminating on the emergence of three waves of aging.”

The level of proteins remains constant for a while then they tend to shift in three stages at young adulthood, late middle age, and in old age, coming in waves in the proteome in the fourth, seventh, and eighth decades of life, which reflects distinct biological pathways and reveals differential associations with the genome and proteome of age-related disease and phenotypic traits. 

The rapid changes appeared to happen in a distinct synchronized fashion with the big changes in multiple proteins appearing at around the age of 34, 60, and 78 which suggests the possibility of the body changing its biological programming significantly at around these ages. Discovery has the potential to open new doors to research what is happening and whether these changes could possibly be delayed, stopped, reversed, or slowed down to fight the aging process to improve healthspan and longevity. 

“We’ve known for a long time that measuring certain proteins in the blood can give you information about a person’s health status - lipoproteins for cardiovascular health for example,” explains neurologist Tony Wyss-Coray. “But it hasn’t been appreciated that so many different proteins’ levels -  roughly a third of all the ones we looked at - change markedly with advancing age.”

“The profiles changed at these times. I would think of it as hard numbers, but rather that there are stops along the way to the destination (obsolescence) that are major pit stops that reflect where you have come and how close you are to the end of the journey. In other words, there are clear signs that represent you have moved to the next level of aging, and that aging is not a blind continuum. It appears aging can progress in a stepwise manner where you reach a tipping point where enough proteins are altered in the profile to push you to that next stage of aging,” explains Mark Miller, president of Kaiviti Consulting. 

Miller adds that these stops don’t appear to be classic stops in very healthy individuals as they fail to display the shifts in protein profiles that are typically seen with aging, “However, the 379 high target proteins cover many bases from metabolism, immunity, cardiovascular health, etc.”

Although the findings are early, men and women are also suggested to age differently; of the 1,379 proteins found to change with age, nearly two-thirds were more predictive for one sex when compared to the other. Any clinical applications are still several years off as it will require much work to examine these proteins to determine how they are markers for aging and whether or not they contribute to the aging process. 

Findings reveal the possibility of one day having a blood test to measure how well we are aging at the cellular level, and the more one knows about growing older, the more that can be done to take steps to try and counteract the process to extend longevity as well as identify treatments to combat age-related conditions. 

“Proteomics provides new insight, but it is too early to say how predictive it will be,” says Miller. “Nevertheless, the results are encouraging and most certainly insightful.” “While it is still in the early days the results are revealing, but we need to examine proteomics together with other detailed, high-intensity screening activities. To appreciate the whole picture, we need to assess genetics, epigenetic, microbiome profile, and metabolomics where diet, metabolism, and the microbiome intersect. From there we get a true picture of health, wellness, lifestyle, and aging.”

"Ideally, you'd want to know how virtually anything you took or did affects your physiological age," says Wyss-Coray.