Muscles carry an olfactory receptor that protects them from aging: activating it restored strength and mass in old mice
Muscles carry an olfactory receptor that protects them from aging: activating it restored strength and mass in old mice
On September 21, a preprint reported that the olfactory receptor OR10J5, the same gene that detects odors in the nose, also functions in muscle, where it protects against aging. In old mice, activating it with the compound lyral restored muscle mass, grip strength, and endurance; without the gene, the effect disappeared. Lyral reproduced the same result in muscle cells derived from human embryonic stem cells.
With age, muscles lose mass and strength. Sarcopenia raises the risk of falls, fractures, and loss of independence in older adults. No approved drug exists for it: two weeks earlier, a review of seven sarcopenia treatment mechanisms did not mention olfactory receptors. The new target was identified by the team of Yousin Suh, a Columbia University professor and human longevity geneticist.
Humans carry roughly 400 olfactory receptor genes, the largest gene family in the genome. Nearly all of them function only in the nose; a few have a second life in other organs. OR10J5 is one of them: it helps progenitor cells repair muscle injuries, and activation by a different compound has previously increased muscle mass in healthy mice. Since the receptor governed muscle growth and repair, checking whether it also protects muscle from aging was a natural next step, but no answer existed.
OR10J5 activity declines during cellular senescence and atrophy, in both mouse and human cell cultures and in atrophied and naturally aged muscles. When the gene was fully knocked out, mice lost mass, grip strength, and endurance faster than normal with age, and markers of cellular senescence increased.
The reverse experiment tested whether reactivating the receptor could restore youthfulness to aging muscle. Old mice (82 weeks, a substantial age for a mouse) received lyral injections for eight weeks to activate OR10J5. In normal old mice, this restored muscle mass, grip strength, and endurance to youthful levels and reduced senescence markers in the tissue. In mice lacking the OR10J5 gene, lyral had no effect, confirming that the improvement works specifically through this receptor.
At the cellular level, OR10J5 sits in the membrane. When activated, it triggers signaling through the second messenger cAMP, and lyral engaged this pathway. Downstream, the signal upregulated genes for mitochondrial biogenesis and suppressed inflammation in senescent cells, addressing the energy deficit and inflammation that exhaust aging muscle.
The result also replicated in human material: lyral had no effect on young cells, but in cells that had senesced after many divisions, it improved fusion into mature fibers and reduced markers of senescence.
"These results reveal an unexpected role for an ectopic olfactory receptor in aging and cellular senescence of skeletal muscle," the authors write.
Lyral itself is a synthetic fragrance compound, banned in EU cosmetics since 2019–2021 as the leading cause of fragrance contact allergy. The mice received it by injection, not topical application.
"The present results provide pharmacological proof of principle for OR10J5 activation, rather than establishing lyral itself as a therapeutic candidate," the authors write.
OR10J5 is a rare case in which an aging target has been shown to be both necessary (knockout accelerates aging) and sufficient (activation reverses it), with the finding extending to human cells. Olfactory receptors also recognize a narrow and well-characterized set of natural ligands, so finding a safe replacement for lyral is more a matter of screening known candidates than of discovering the target itself from scratch.