Illustration depicting the reversal of aging through young blood extracellular vesiclesIntroduction

Recent research published in the journal Nature Aging has uncovered an intriguing potential anti-aging therapy: small extracellular vesicles (sEVs) derived from young blood plasma. A groundbreaking study published in Nature Aging demonstrates that these tiny membrane-bound particles can reverse multiple hallmarks of aging and improve physiological function across various tissues in aged mice.

Key Findings on sEVs Impact

Improve Lifespan Extension and Overall Health

The most striking result was that weekly injections of young sEVs extended the median lifespan of aged mice by 12.42%. Beyond just living longer, the sEV-treated aged mice maintained a much healthier appearance with improvements in coat quality and reduced frailty scores. This suggests young sEVs can broadly counteract age-related decline across multiple systems.

Significantly Improve Cognitive Function and Brain Health

Young sEV treatment led to significant improvements in learning, memory, and cognitive performance in aged mice:

  • Enhanced spatial memory and learning in the Morris water maze test.
  • Improved contextual fear conditioning indicating better hippocampus-dependent memory.
  • Increased hippocampal and cortical volumes reversing age-related brain atrophy.
  • Reduced senescence markers and increased proliferation of neural progenitor cells.

The cognitive benefits appeared to stem from improved mitochondrial function and energy metabolism in brain tissues. Young sEVs increased ATP production, mitochondrial enzyme activity, and mitochondrial DNA content in the hippocampus.

Enhance Muscle Function and Exercise Capacity

Sarcopenia and reduced exercise tolerance are hallmarks of aging. Young sEV treatment counteracted these effects:

  • Increased treadmill running time to exhaustion by 47.6% in aged mice.
  • Enhanced mitochondrial function and ATP production in muscle tissue.
  • Increased muscle fiber mitochondrial content.
  • Reduced markers of cellular senescence in muscle.

These improvements in muscle energetics and function likely underlie the dramatic boost in exercise capacity.

Remediate Cardiovascular Health

Aging is associated with left ventricular hypertrophy and declining cardiac function. Young sEV treatment improved several echocardiography parameters in aged mice:

  • Reduced left ventricular mass.
  • Increased ejection fraction and fractional shortening.
  • Decreased end-diastolic and end-systolic volumes.

These changes indicate improved cardiac structure and contractile function with young sEV treatment.

May Help in Maintaining Bone Health

Accelerated bone loss is a major concern in aging. Micro-CT analysis revealed young sEVs could partially reverse age-related bone deterioration:

  • Increased bone volume/total volume ratio.
  • Higher trabecular number.
  • Reduced trabecular separation.

This suggests young sEVs may help maintain bone density and microarchitecture with age.

Boost Metabolic Health

Declining metabolic rate and energy expenditure are features of aging. Young sEV treatment increased several metabolic parameters in aged mice:

  • Higher oxygen consumption and carbon dioxide production.
  • Increased heat production.
  • Enhanced locomotor activity.

These changes reflect an overall boost in metabolic health and energy utilization.

Rejuvenate Male Fertility

Male reproductive function declines with age. Young sEV treatment partially restored several aspects of male fertility in aged mice:

  • Increased sperm count and motility.
  • Improved sperm DNA integrity.
  • Enhanced embryo implantation rates when mated with young females.
  • Increased litter sizes.

This indicates young sEVs can partially rejuvenate the male reproductive system.

Reduce Cellular Senescence

Accumulation of senescent cells is a key driver of aging. Young sEV treatment reduced multiple markers of cellular senescence across tissues:

  • Decreased senescence-associated β-galactosidase activity.
  • Reduced expression of senescence markers p16 and p21.
  • Lower levels of reactive oxygen species and advanced glycation end-products.
  • Decreased lipofuscin accumulation.

By reducing the senescent cell burden, young sEVs likely improve overall tissue function and health.

Enhance Mitochondrial Function

Impaired mitochondrial function is central to many aspects of aging. Young sEVs broadly enhanced mitochondrial health across tissues:

  • Increased ATP production.
  • Enhanced activity of respiratory chain complexes.
  • Higher mitochondrial DNA copy number.
  • Improved mitochondrial ultrastructure and morphology.

This mitochondrial rejuvenation appears to be a key mechanism underlying the multi-system benefits of young sEV treatment.

Specific MicroRNA Cargoes

The study identified specific microRNA cargoes in young sEVs that mediate their rejuvenating effects:

  • miR-144-3p, miR-149-5p, and miR-455-3p were enriched in young sEVs.
  • These miRNAs increased the expression of PGC-1α, a master regulator of mitochondrial biogenesis.
  • Blocking these miRNAs abolished the beneficial effects of young sEVs.

This reveals a specific molecular pathway by which young sEVs can reprogram aged cells to a more youthful state.


This landmark study demonstrates that young blood-derived sEVs can counteract multiple hallmarks of aging across diverse tissues and physiological systems. By delivering specific rejuvenating miRNA cargoes, these tiny vesicles appear to reset cellular energetics and mitochondrial function to a more youthful state. While much work remains to translate these findings to humans, sEVs represent an exciting potential therapeutic approach to extend health span and combat age-related decline.

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