Key Points:
- Study participants who received plasma exchange therapy exhibited an average lowered biological age of 1.32 years.
- Participants who underwent injections of a concentrated solution with human antibodies (intravenous immunoglobulin therapy) in addition to therapeutic plasma exchange showed an average biological age reduction of 2.61 years.
- Individuals with markers of poorer health status, such as higher levels of circulating glucose, saw the greatest reductions in biological age.
In a first-of-its-kind human study published in Aging Cell, Furman and colleagues from the Buck Institute for Research on Aging show that removing and replacing blood plasma with a fresh solution (therapeutic plasma exchange) confers about a 1.32-year reduction in biological age. Additionally, combining therapeutic plasma exchange with injections of a concentrated solution of human antibodies (intravenous immunoglobulin therapy) reduced biological age an average of 2.6 years. Moreover, study participants with markers of poorer health status, like higher levels of circulating glucose, achieved the greatest reductions in biological age. These findings support the notion that people can use therapeutic plasma exchange to enhance longevity and possibly extend years lived without a debilitating disease (a concept known as healthspan).
Therapeutic plasma exchange, first studied in animal models in 1914, has been shown to benefit various health conditions, including COVID-19. Interestingly, up to 65% of patients with COVID-19 who received therapeutic plasma exchange showed improvements in fatigue, stamina, and brain fog. This finding raises the question of whether, in addition to treating conditions like COVID-19, therapeutic plasma exchange confers benefits against aging, such as improving physical and cognitive function.
In the context of aging, UC Berkeley researchers have previously demonstrated that five rounds of therapeutic plasma exchange can lower proteins in circulation associated with aging. However, no studies performed to date had used clocks that analyze DNA molecular tagging patterns to estimate biological age (epigenetic clocks) to confirm rejuvenating effects from therapeutic plasma exchange. Accordingly, in their breakthrough study, Furman and colleagues utilized 36 epigenetic clocks to estimate rejuvenation following therapeutic plasma exchange in 44 adults over 50 years old.
“Unfortunately, most so-called ‘longevity interventions’ lack proven effectiveness in humans. By conducting clinical trials, we aim to change that—this study marks the first step in demonstrating that plasma exchange can significantly improve key mechanisms of biological aging,” said David Furman, PhD, senior author of the study, in a press release.
Therapeutic Plasma Exchange Significantly Reduces Biological Age, Especially When Combined with Intravenous Immunoglobulin Therapy
To find whether therapeutic plasma exchange can reverse biological age, 44 adults over age 50 were enrolled into three different treatment groups.
- In one group (TPE + IVIG), 11 participants were administered therapeutic plasma exchange with intravenous immunoglobulin therapy twice for one week each month for a total of three months.
- In another group (TPE 2X), 11 participants were given two therapeutic plasma exchange treatments in one week every month for three months.
- A third group of 11 participants (TPE 1X) was given one therapeutic plasma exchange treatment a month for six months.
- Finally, another group of 11 participants for comparison (Sham) was given a placebo either two times in one week every month or once in a week every month for six months.
Furman and colleagues measured the biological age of each treatment group using epigenetic biological age assessments. Interestingly, the TPE 1X group exhibited an average biological age reduction of 1.32 years across all epigenetic age assessments, the most pronounced effect among the two TPE groups. This result suggests that therapeutic plasma exchange, especially when spaced out once a month, significantly reduces biological age.
Importantly, the TPE + IVIG group, who experienced intravenous immunoglobulin therapy in addition to therapeutic plasma exchange, displayed an average biological age reduction of 2.61 years. This finding suggests that intravenous immunoglobulin therapy, which purportedly boosts the immune system, can further reduce biological age when added to therapeutic plasma exchange.
To assess what groups of adults might be more responsive to potential rejuvenating effects from therapeutic plasma exchange, Furman and colleagues searched for correlations between physiological markers of poor health and reductions in biological age. Intriguingly, the researchers found that participants with poorer health status, as suggested by higher levels of blood glucose and proteins indicative of liver disease, showed the greatest reductions in biological age. These findings suggest that individuals with poorer health status may benefit the most from therapeutic plasma exchange.
A Reduced Biological Age from Therapeutic Plasma Exchange Suggests Rejuvenating Effects
Furman and colleagues’ study marks the first confirmation with epigenetic age assessments that therapeutic plasma exchange significantly lowers biological age in older adults. A lower biological age, as assessed with epigenetic age tests, is associated with a reduced likelihood of age-related diseases, such as cardiovascular problems. This supports the notion that a significantly reduced biological age indicates some degree of physiological rejuvenation from therapeutic plasma exchange.
Importantly, adding intravenous immunoglobulin therapy, a way to possibly boost immunity, conferred a more significant reduction in biological age. While the precise mechanism by which intravenous immunoglobulin therapy combined with therapeutic plasma exchange reduces biological age remains open for debate, the study’s data support that the combination of these procedures also reduces systemic inflammation, one of the hallmarks of aging. Thus, it could be that lowering inflammation with intravenous immunoglobulin therapy adds to therapeutic plasma exchange’s effects to further lower biological age.
“Our findings show that plasma exchange and intravenous immunoglobulin are a powerful tool for biological age rejuvenation and provide compelling evidence that targeted plasma interventions can impact age-related molecular changes,” said Eric Verdin of the Buck Institute for Research on Aging, one of the study’s authors.
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