Study: Metformin and leucine prevent cellular senescence and proteostasis disruption

Medical Xpress / Impact Journals LLC / Aging ^ | April 3, 2023 | Jonathan J. Petrocelli et al

[ConservativeMind]

Aging coincides with the accumulation of senescent cells within skeletal muscle that produce inflammatory products, known as the senescence-associated secretory phenotype, but the relationship of senescent cells to muscle atrophy is unclear. Previously, researchers found that a metformin + leucine (MET+LEU) treatment had synergistic effects in aged mice to improve skeletal muscle structure and function during disuse atrophy.

In this new study, researchers aimed to determine the mechanisms by which MET+LEU exhibits muscle atrophy protection in vitro and if this occurs through cellular senescence.

C2C12 myoblasts differentiated into myotubes were used to determine MET+LEU mechanisms during atrophy. Additionally, aged mouse single myofibers and older human donor primary myoblasts were individually isolated to determine the translational potential of MET+LEU on muscle cells. MET+LEU (25 + 125 μM) treatment increased myotube differentiation and prevented myotube atrophy.

Low concentration (0.1 + 0.5 μM) MET+LEU had unique effects to prevent muscle atrophy and increase transcripts related to protein synthesis and decrease transcripts related to protein breakdown. Myotube atrophy resulted in dysregulated proteostasis that was reversed with MET+LEU and individually with proteasome inhibition (MG-132).

Inflammatory and cellular senescence transcriptional pathways and respective transcripts were increased following myotube atrophy yet reversed with MET+LEU treatment. Dasatinib + quercetin (D+Q) senolytic prevented myotube atrophy similar to MET+LEU. Finally, MET+LEU prevented loss in myotube size in alternate in vitro models of muscle atrophy as well as in aged myofibers while, in human primary myotubes, MET+LEU prevented reductions in myonuclei fusion. These data support that MET+LEU has skeletal muscle cell-autonomous properties to prevent atrophy by reversing senescence and improving proteostasis.

"In conclusion, this study provides evidence of a possible link between cellular senescence and disrupted proteostasis that is targeted by MET+LEU in muscle cells to reverse the muscle atrophy phenotype," stated the authors.

[ConservativeMind]

If you are already on Metformin for high blood sugar, make sure you eat high leucine foods or consider supplementing, to get the added benefit of your muscles staying robust, longer than normal.

Navy beans, cottage cheese, pumpkin seeds, and cottage cheese are examples of high leucine foods.

[ConservativeMind]

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[Valpal1]

Or just eat carnivore. Chicken, beef, pork and tuna are the top 4 high luecine foods

[ckilmer]

I wonder if berberine will do the same thing as metformin in combination with leucine.

(probably not)

[texas booster]

BTTT.

Metformin + leucine = muscular and skeletal benefits.

[COBOL2Java]

[bert]

Metformin inhibits B12

Massive dose of B 12 along with the metformin will cause the fog to lift

[COBOL2Java]

I take 1000 mcg of B12 a day. Recommended by my endocrinologist.