Biological age — the measure of how fast your body and cells are aging — reflects the body’s overall health and functional state at the cellular, tissue, and organ levels. It’s often considered a more reliable indicator of longevity than chronological age, and it is measured using biomarkers. Increasingly, those biomarkers are being found in blood, and researchers are discovering that blood has a lot to reveal about health, longevity, and aging.
Blood and Biomarkers
“The biological aging process is very complex,” says biologist Maria Moreno-Villanueva, PhD, head of the Exercise Physiology Laboratory at the University of Konstanz in Germany. “It affects all of the body’s tissues and organs, and it is not the result of a single cause. As a result, single biomarkers are not enough to reliably determine a person’s biological age.”
Dr. Moreno-Villanueva and a team from the University of Konstanz identified the need to develop simpler, more reliable tests to measure biological age. Using a new blood-scanning technique to identify specific biomarkers, they’ve discovered 10 different blood markers that may help predict biological aging.
The researchers started by measuring 362 different parameters in the blood samples of 3,300 people aged between 35 and 74. They then narrowed these biomarkers down to the 10 most important, with separate sets selected for males and females due to differences in how men and women age.
Each biomarker, covering chemical, genetic, cellular, and molecular signaling pathways, was compared against chronological age, giving researchers a profile of what someone’s blood tends to look like at specific ages. When a person’s blood “age rating” differs significantly from their actual age, it may indicate faster or slower biological aging.
The blood tests were then run on groups of people known to age faster or slower biologically — including people with Down Syndrome (trisomy 21), smokers, and women on hormone therapy. The tests successfully identified the expected aging patterns, suggesting that the biomarkers were being interpreted correctly.
“Against the backdrop of current research on the aging effects of smoking, hormone replacement therapy, or trisomy 21, all of these results are plausible and confirm the validity of our bioage score,” says Alexander Bürkle, MD, professor of molecular toxicology at the University of Konstanz.
The study found that certain biomarkers seem to contribute to biological aging (described as the “drivers”) while others are only indicators of it (the “bystanders”). This information has the potential to provide deeper insight into the health of a patient, making the newly developed test useful across a wide range of clinical applications.
Survival in the Blood
For researchers from Duke University and the University of Minnesota, a blood test has emerged as a potential way to predict a patient’s chances of surviving at least two more years, forecasting short-term survival with 86% accuracy in older adults.
“Our work has long focused on understanding the body’s intrinsic repair mechanisms,” said Virginia Byers Kraus, MD, PhD, distinguished professor of medicine, pathology, and orthopedics at Duke University School of Medicine, Durham, North Carolina, and senior author of the multi-year study, which examined more than a thousand blood samples from adults aged 71 years or older.
“In 2019, we observed that some human cartilage — such as osteoarthritic cartilage of the ankle — has a surprising ability to repair itself, whereas other joints, like the osteoarthritic cartilage of the hip, do not.”
That observation led the team to identify small noncoding RNAs, including both miRNAs (microRNAs) and piRNAs, that appeared to drive cartilage repair. In the current study, they broadened their research to determine whether these (or related small RNAs) could also influence overall human health and survival.
“To explore this, we measured circulating small RNAs in a large cohort of older adults,” explained Dr. Kraus. “While the cartilage-regenerative RNAs themselves were not linked to survival, we identified a distinct set of small RNAs — particularly piRNAs — that showed strong and potentially causal relationships with survival outcomes. This now focuses our attention on piRNAs as an important and previously underappreciated class of molecules in human aging.”
Discovered by Haifan Lin, PhD, professor of cell biology and genetics at Yale School of Medicine and founding director of the Yale Stem Cell Center, piRNAs are known to be present in the innate immune defense system and may exist in somatic cells.
According to Florence Comite, MD, a New York City-based endocrinologist and founder of the Comite Center for Precision Medicine & Healthy Longevity, “Various small RNA molecules are thought to regulate processes that affect aging, such as insulin resistance/insulin growth factor and the stress response mechanism which modulate longevity across species, but little else is known in humans.”
Dr. Lin says that “piRNAs play a crucial role in silencing transposable elements, thereby protecting genome integrity in germ cells.” His discovery of piRNAs “opened an entirely new field of research, and it continues to inform and inspire our efforts to understand how small RNA pathways safeguard genome integrity and regulate cell fate.”
Dr. Kraus and her team expanded upon those efforts in their recent study, observing the broader roles circulating piRNAs may play in aging and longevity. They divided the North Carolina cohort into two groups, aiming to determine whether small RNAs were associated with survival and to identify the most practical way to analyze the data.
“Interestingly, we found that simple, untransformed counts performed very well and revealed a strong signal associated with survival,” she said. “We then tested these findings in the second half of the cohort, treating it as an entirely independent study for purposes of validation.”
They researchers processed and sequenced the samples separately to create a stringent validation process and found the results highly consistent across all stages. Predictive performance was more pronounced over short time horizons (two-year survival) and declined over longer timeframes (five-year and ten-year survival).
Concluding Thoughts
The already essential role blood plays in health is expanding as researchers discover how to unlock its secrets and interpret its clues. Blood biomarkers are revealing information about biological age and our ability to survive, and more information about the connections between blood, longevity, and healthspan seem to be on their way.
Sources: There Are 10 Signs of Faster Aging Hidden in Your Blood, Study Says Blood as the Mirror and Modulator of Aging: Mechanistic Insights and Rejuvenation Strategies