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Utilizing a Biological Aging Biomarker to Predict Spine Surgery Outcomes

A new pilot study led by a USC Spine Center surgeon identified an association between shortened telomere length and postoperative complications after major spine surgery. These results could lead to a new future of risk assessment by studying a patient’s biological age. 


A wide range of variables can affect the outcomes of spinal reconstruction surgeries, especially given the complexity of the human spine and potential neurologic complications.

In recent years, spine surgeons have identified “frailty” as a novel metric for evaluating the accumulation of health deficits that occur over time and may impact patient outcomes.

But the current tools for quantifying and assessing frailty can have limitations. Additionally, most formal guidelines for preoperative optimization focus on controlling modifiable factors, such as lowering hemoglobin A1c in diabetics, or smoking cessation in smokers.

Michael Safaee, MD, a spine surgeon at the USC Spine Center at Keck Medicine of USC, recently embarked on a pilot study to identify a potential biomarker for evaluating patients’ risk prior to major spinal surgery.

The results, published in the Journal of Neurosurgery: Spine in March 2023, revealed that biological age, rather than chronological age, may better predict the risk of a major medical or surgical complication after complex spine surgery.

“My goal is to apply knowledge and strategies from other disciplines towards spine surgery,” Dr. Safaee said. “For example, we treat tumors based on their molecular signatures, so I thought that we could apply those same principles to patients undergoing spine surgery, treating them based on biological age and potentially other yet-to-be-discovered biomarkers.”

Telomere length as a potential new tool for risk stratification 

The pilot study assessed the length of telomeres — DNA-protein complexes that shorten with chronological age and environmental exposures — in 43 adult patients undergoing elective surgery for spinal deformities.

The study then compared complications occurring within 90 days after surgery with the data gathered on telomere length prior to each patient’s operation.

To quantify telomere length, Dr. Safaee and his team extracted white blood cells from blood samples taken before surgery, further isolated the patients’ DNA and used special amplification reactions to measure the telomere length.

While further studies are needed, results showed an association between short telomere length and increased risk of postoperative complications, despite non-significant differences in the patients’ chronological age. The difference in chronological age was five years, compared to nine to ten years of difference when using telomere length analysis.

Patients with the shortest telomere lengths also had the highest risk.

According to Dr. Safaee, telomere length could provide a more patient-specific tool for evaluating risk compared to existing tools such as the American Society of Anesthesiologists Classification and the Charlson Comorbidity Index. In the future, he said, surgeons could combine these tools for improved risk stratification.

“Patient-specific biomarkers could, in theory, provide insight into one’s ability to respond to the stresses of surgery,” Dr. Safaee said.

Increase in lifespans creates greater need for risk evaluation

Evaluations of biological age may prove invaluable as life spans increase, thanks to advanced treatments for infections, cancer and cardiovascular disease.

Having more specialized tools for identifying potential risk factors is especially beneficial for spine surgeons, who need to consider potential neurologic complications when recommending surgery to patients. Although rare, certain complex spine surgeries carry a small risk of spinal cord injury or weakness.

Currently, spine surgeries are in greater demand than ever due to breakdowns of the musculoskeletal system in patients reaching inevitable stages of late-life morbidity.  

“When the spine degenerates, it doesn’t just cause pain,” Dr. Safaee said. “These degenerative processes can also cause weakness, bowel and bladder dysfunction, and other neurologic impairments.”

With the pilot study’s new findings, Dr. Safaee believes that biological age could help spine surgeons better counsel patients on their level of frailty ahead of surgery and allow them to make more informed decisions about their care strategy.

“We’re never going to withhold treatment from a patient based on their biological age,” Dr. Safaee said. “But in a future world where we have more data and can more accurately predict the likelihood of a complication, we can tailor treatment to a patient’s biology and risk tolerance.”

Knowledge of increased risk could change patient outlook

For patients whose biological age indicates increased risk, application of the new findings could prompt surgeons to explore less invasive measures or to recommend more intensive preoperative preparation, such as physical therapy.

“During our large spinal reconstruction surgeries, even though patients are asleep under anesthesia, their body is going through the physiologic equivalent of running a marathon,” Dr. Safaee said. “For a patient with older biological age, you may take more time to optimize them before surgery, just like training before a marathon.”

Dr. Safaee also sees the potential benefit of biological age as a metric for patients approaching general wellness in the future, including stress management and understanding one’s own genetic predispositions.

“At the USC Spine Center, one of our ultimate goals is to provide patients with data on their biological age,” Dr. Safaee said. “It may even give them the motivation to live a healthier lifestyle.”

Note: This work was done during Dr. Safaee’s time as a chief resident at the University of California, San Francisco, with his mentor and co-author Christopher Ames, MD, an international leader in management of complex adult spinal deformity.