The Rapamycin replacement? Extracellular vesicles from young plasma reverse age-related functional declines

Ok, I know the general topic has been covered before. Here is yet another research paper. I think this may be the most promising, closest at hand new aging intervention.

Small extracellular vesicles from young plasma reverse age-related functional declines by improving mitochondrial energy metabolism

Recent investigations into heterochronic parabiosis have unveiled robust rejuvenating effects of young blood on aged tissues. However, the specific rejuvenating mechanisms remain incompletely elucidated. Here we demonstrate that small extracellular vesicles (sEVs) from the plasma of young mice counteract pre-existing aging at molecular, mitochondrial, cellular and physiological levels. Intravenous injection of young sEVs into aged mice extends their lifespan, mitigates senescent phenotypes and ameliorates age-associated functional declines in multiple tissues. Quantitative proteomic analyses identified substantial alterations in the proteomes of aged tissues after young sEV treatment, and these changes are closely associated with metabolic processes. Mechanistic investigations reveal that young sEVs stimulate PGC-1α expression in vitro and in vivo through their miRNA cargoes, thereby improving mitochondrial functions and mitigating mitochondrial deficits in aged tissues. Overall, this study demonstrates that young sEVs reverse degenerative changes and age-related dysfunction, at least in part, by stimulating PGC-1α expression and enhancing mitochondrial energy metabolism.


Ah - Just one more thing to add to the stack :wink:

And Yes - similar to this research: Reversal of Biological Age in Multiple Rat Organs by Young Porcine Plasma Fraction


With any luck, someone will figure out the specific elements that are involved & package them in a way we can get them at the local pharmacy …


For now it looks like you need a real thing young EVs to be packaged as weekly weekly injectable.

Impressive, really. Comparable to rapamycin lifespan extension benefits but with no negative side effects like e,g. reduced fertility, which rapamycin has and this treatment actually improves. The delivery as once a week injectable EVs also seems straightforward.

A writeup by Lifespan IO:


Chinese scientists claim to find new life for old in the blood of the young | South China Morning Post


Some interesting new, related research, out of Columbia University Medical School:

In vitro heterochronic parabiosis identifies pigment epithelium-derived factor as a systemic mediator of rejuvenation by young blood

Xizhe Wang, Cagdas Tazearslan, Seungsoo Kim, Qinghua Guo, Daniela Contreras, Jiping Yang, Adam D Hudgins and Yousin Suh

Several decades of heterochronic parabiosis (HCPB) studies have demonstrated the restorative impact of young blood, and deleterious influence of aged blood, on physiological function and homeostasis across tissues, although few of the factors responsible for these observations have been identified. Here we develop an in vitro HCPB system to identify these circulating factors, using replicative lifespan (RLS) of primary human fibroblasts as an endpoint of cellular health. We find that RLS is inversely correlated with serum donor age and sensitive to the presence or absence of specific serum components. Through in vitro HCPB, we identify the secreted protein pigment epithelium-derived factor (PEDF) as a circulating factor that extends RLS of primary human fibroblasts and declines with age in mammals. Systemic administration of PEDF to aged mice reverses age-related functional decline and pathology across several tissues, improving cognitive function and reducing hepatic fibrosis and renal lipid accumulation. Together, our data supports PEDF as a systemic mediator of the effect of young blood on organismal health and homeostasis and establishes our in vitro HCPB system as a valuable screening platform for the identification of candidate circulating factors involved in aging and rejuvenation.

bioRxiv. posted 5 May 2024, 10.1101/2024.05.02.592258

I hope that a lot of the “million molecules” are coming from these vesicles.


This is how some exosomes are produced.

MSCs from umbilical cord blood are used.

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