Abstract
The present study assessed the body composition trajectory of rats (N = 96) placed into 5 groups according to lifespan, using dual-energy x-ray absorptiometry every 6 months until end-of-life. A striking linearity between lifespan and bone mass percentage (not absolute bone mass) was observed. Long-lived rats show a higher bone mass percentage with a delayed insulin rise to a similar peak level as short-lived counterparts, followed by insulin declines and bone mass loss. Decreasing insulin after streptozotocin (STZ) injection caused a rapid bone mass loss (-10.5%) with a decreased 5-day survival rate to 35% in old rats (20 months). Insulin replacement to STZ-injected rats completely blocked bone mass loss and increased the survival rate to 71%. Normal old rats (20 months) had faster lean mass loss despite greater myofiber regeneration (centronucleation) compared with the young rats (4 months). Increased CD68+ and CD163+ cell infiltration into insulin-depleted muscle suggests a bone marrow cell exhaustion by aging muscle. Bone produces stem cells and phagocytes to continuously rejuvenate peripheral tissues. Our data suggests that aging and unsustainable life is associated with development of disproportionality between bone and the growing body size, partly due to insulin reversal from hyperinsulinemia during late life.
Highlights
Multicellular organisms may be viewed as society-like system made by living cells, where increased survival fitness comes from large-scale cooperation among highly differentiated cells
We firstly examined relationship between body composition and insulin levels every 6 months until 24 months of age among laboratory rats
Long-lived rats are characterized by the modest weight gain for the first three quarters of life followed by delayed weight loss until the end of life compared to the rest groups
Summary
Multicellular organisms may be viewed as society-like system made by living cells, where increased survival fitness comes from large-scale cooperation among highly differentiated cells. Cells within a multicellular mammal are mostly short-lived [1]. Positive balance between cell death and cell proliferation is crucial for sustaining weight growth in a way similar to population curve. The weight reversal during late life represents a shift from positive to negative balance between cell proliferation and cell death, since animal weight is, in large part, determined by cell number [2]. Body composition continues to change during a protracted weight gain period followed by a short weight loss period before death, representing an imbalanced development among differentiated cells in an expanding and shrinking multicellular system. The relative importance of bone, muscle, and fat to sustain the longest survival duration of multicellular systems has not been strictly defined by a whole-life approach observation covering the weight loss periods of end-life
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