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Aging & Longevity

Cedars-Sinai Scientists Identify Stem Cell-Secreted Particles that Boost Lifespan and Endurance 

Particles secreted from stem cells called extracellular vesicles (EVs) prolong the lifespan of old rats while improving their exercise capacity and heart function.

By Daniel R. Miranda, Ph.D.

Key Points: 

  • Old rats injected with stem cell EVs from newborn rats exhibit 60% higher survival rates. 
  • Young EVs improve the treadmill exercise capacity of old rats. 
  • Old rat heart function is significantly improved by treatment with young EVs. 

Today it seems possible to treat multiple age-related diseases, including cardiovascular disease and diabetes with a single treatment. Now researchers from Cedars-Sinai Medical Center in Los Angeles may have discovered such a treatment. 

As reported in Scientific Reports, Shamagian and colleagues show that stem cell EVs prolong the lifespan of old rats. They also show that EVs improve the exercise capacity and heart function of old rats while reducing damage to the heart, skeletal muscle, lungs, and kidneys. These findings suggest that EVs can potentially target multiple age-related diseases.  

Stem Cell Extracellular Vesicles Counter Aging 

Scientists have suspected that EVs — which are secreted into the blood and affect the entire body — contribute to the rejuvenating effects of young blood. For this reason, Samagian and colleagues isolated heart stem cell EVs from newborn rats. The EVs were then injected into old (22-month-old) rats to determine their rejuvenation effects. 

After 16 weeks, 91.7% of the EV-treated old rats survived, whereas only 57.1% of the untreated old rats survived. On average, EV treatment delayed death by 54 days, which is equivalent to about 3.2 human years. The most frequent cause of death was leukemia, accounting for 50% of deaths in untreated old rats and 28% in EV-treated old rats. 

Extracellular Vesicles (EVs) Extend Lifespan. After 16 weeks, 91.7% of rats treated with EVs (blue) survived, while only 57.1% of untreated rats (red) survived.
(Shamagian et al., 2023 | Scientific Reports) Extracellular Vesicles (EVs) Prolong Lifespan. After 16 weeks, 91.7% of EV-treated rats (blue) survived, whereas only 57.1% of untreated rats (red) survived.

To determine the exercise capacity of the old rats, Shamagian and colleagues challenged the rats to treadmill running every 4 weeks. To exhaust the rats, the speed of the treadmill was increased every 3 minutes, and the distance the rats ran before exhaustion was measured. After the first 4 weeks, the EV-treated old rats ran a 16% longer distance than untreated rats. This increase in distance persisted over 16 weeks, suggesting that EVs improve exercise capacity. 

Extracellular Vesicles (EVs) Enhance Exercise Capacity. At 4 weeks, rats treated with EVs (blue) demonstrated a 16% longer running distance compared to untreated rats (red), and this improvement persisted over 16 weeks, indicating enhanced exercise capacity.
(Shamagian et al., 2023 | Scientific Reports) Extracellular Vesicles (EVs) Improve Exercise Capacity. At 4 weeks, EV-treated rats (blue) ran a 16% longer distance than untreated rats (red), which persisted over 16 weeks, suggesting improved exercise capacity.

To assess heart function, Shamagian and colleagues measured the velocity of blood flow between chambers of the heart. They found that old rats had reduced blood flow velocity, indicating stiffness and a lack of heart muscle relaxation. However, EV treatment increased blood flow velocity, suggesting that EVs can restore heart function in old rats. 

Extracellular Vesicles (EVs) Improve Heart Function. In untreated old rats (red), there is lower inner heart blood flow velocity (Δ E’). Conversely, the blood of EV-treated old rats (blue) flows faster, signifying enhanced heart function.
(Shamagian et al., 2023 | Scientific Reports) Extracellular Vesicles (EVs) Restore Heart Function. Untreated old rats (red) have lower inner heart blood flow velocity (Δ E’). However, the blood of EV-treated old rats (blue) flows faster, indicating improved heart function.

Overall, the findings of Shamagian and colleagues suggest that heart stem cell EVs from newborn rats rejuvenate the hearts of old rats, improving their exercise capacity and prolonging their lifespan. Furthermore, the researchers showed that EVs reduce damage to multiple organs (i.e. heart, lung, kidney, and skeletal muscle), suggesting that young EVs possess rejuvenation effects similar to transferring blood from younger to older organisms (heterochronic parabiosis). 

Anti-Aging EVs 

EVs secreted by stem cells contain a host of molecules capable of thwarting the processes that underlie aging. These molecules include growth factors, which were previously used to treat arthritis in rats. EVs also contain microRNAs — short strands of RNA that control whether genes are translated to proteins — which have been shown to remove pesky senescent cells. Furthermore, stem cell EVs have been shown to increase grip strength, and even promote hair regrowth in mice. Therefore, we may see young stem cell EVs and their contents being used as treatments for disease in the near future. 

Source

Grigorian Shamagian, L., Rogers, R. G., Luther, K., Angert, D., Echavez, A., Liu, W., Middleton, R., Antes, T., Valle, J., Fourier, M., Sanchez, L., Jaghatspanyan, E., Mariscal, J., Zhang, R., & Marbán, E. (2023). Rejuvenating effects of young extracellular vesicles in aged rats and in cellular models of human senescence. Scientific Reports, 13(1), 1-12. https://doi.org/10.1038/s41598-023-39370-5

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