Controlled bone loading extended lifespan in aged mice
Controlled bone loading extended lifespan in aged mice
On 23 October, Cell Metabolism published a study in which researchers applied mechanical loads to the tibias of 20-month-old mice under anesthesia over several months. Median lifespan increased, and additional experiments tested whether a signal from bone could travel through the blood and affect measures of aging in other tissues.
Osteocytes, the cells embedded in bone tissue, sense its deformation. Their membranes contain the PIEZO1 channel, which opens in response to stretching and triggers a cellular response. In earlier work, the same research group showed that bone cells release proteins whose levels change with age and mechanical loading. The new study therefore examined whether these signals could influence aging throughout the body.
First, the authors inactivated the Piezo1 gene specifically in osteocytes in adult mice. Median lifespan subsequently fell by 13,2% in males and 10,7% in females, and age-related changes appeared earlier in several tissues. This experiment tested the role of the mechanosensitive channel in bone cells in age-related changes throughout the body.
The researchers then applied mechanical loads to bone. Under anesthesia, both tibias of 20-month-old mice were compressed with a force of 2 N for 300 cycles at 2 Hz, twice a week for four months. Anesthesia and localized loading allowed the researchers to study mechanical signaling from bone independently of walking and muscle activity.
After loading, aged mice performed better on memory and movement tests; measures of metabolism, bone structure, and cellular senescence also changed. In a survival experiment involving 60 animals, median lifespan increased by 9,4%, or 79,5 days. In one experiment, the authors connected the circulatory systems of two mice; in another, they administered plasma from mice that had undergone bone loading. With both approaches, some measures of aging changed in mice whose bones had received no direct loading. These findings support the hypothesis that some of the signal from bone travels through the blood; the relative proportions of immune cell precursors in the bone marrow also changed.
The authors identified PEDF as a possible mediator: its levels in bone and plasma increased after loading, and administering recombinant PEDF to aged mice changed several measures of aging. PEDF remains a candidate link between bone deformation and the systemic response. In the August experiment with Yoda1, PIEZO1 had already been shown to help aged bone respond to loading by forming new tissue. The current study tested whether this same signal accompanies changes in other tissues and in mouse survival.