Ageing has been defined as a global decline in physiological function depending on both environmental and genetic factors.
Now, researchers identify gene transcripts that are similarly regulated during physiological ageing in nematodes, zebrafish and mice.
They observe the strongest extension of lifespan when impairing expression of the branched-chain amino acid transferase-1 (bcat-1) gene in C. elegans, which leads to excessive levels of branched-chain amino acids (BCAAs).
Authors further show that BCAAs reduce a LET-363/mTOR-dependent neuro-endocrine signal, which they identify as DAF-7/TGFβ, and that impacts lifespan depending on its related receptors, DAF-1 and DAF-4, as well as ultimately on DAF-16/FoxO and HSF-1 in a cell-non-autonomous manner.
The transcription factor HLH-15 controls and epistatically synergizes with BCAT-1 to modulate physiological ageing. Lastly and consistent with previous findings in rodents, nutritional supplementation of BCAAs extends nematodal lifespan.
Taken together, BCAAs act as periphery-derived metabokines that induce a central neuro-endocrine response, culminating in extended healthspan.