Whole-life body composition trajectory and longevity: role of insulin

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.

Senolytic effect of high intensity interval exercise on human skeletal muscle

“…Senescent cells are known to release a variety of proinflammatory molecules, collectively termed as the senescence-associated secretory phenotype (SASP), which attracts immune clearance [ 38 ]. Physically inactive individuals may accumulate more senescent cells in peripheral tissues and dilute the bone marrow resource for tissue renewal due to more competition among aged tissues when bone-to-weight ratio increases during growth [ 4 ].…”

“…Therefore, senescent cells are widely detectable in tissues during embryonic stage [ 2 ] and young adulthood [ 3 ]. A dynamic balance between cell regeneration and death is required to maintain youth levels and total cell number of a tissue [ 4 ]. Tissue renewal requires infiltration of stem cells from bone marrow into peripheral tissues to replenish local progenitors [ 5 ].…”

Cordyceps sinensis accelerates stem cell recruitment to human skeletal muscle after exercise

“…Growth in weight is associated with progressive decreases in bone-to-body mass ratio, which may contribute to relative inadequacy of bone marrow cell production to regenerate cell in tissues. 34 Elevated basal inflammation typically witnessed in overweight individuals can increase background demand for CD34 + cells to renew peripheral tissues of individuals with higher cell population. Therefore, it is hard to predict whether pre-exercise Cordyceps supplementation can also accelerate resolution of muscle inflammation for elderly, particularly those with heavier weight.…”

Vascular function in the aging human brain during muscle exertion

“…We have previously reported an age-dependent decrease in bone to body mass ratio during natural growth in middle-age. Thus, the development of imbalance between the bone marrow cell production organ and an expanding body mass may explain the emerged deficit in endothelial cell replacement [ 23 ]. Furthermore, loss of sex hormones at age 50 y in men [ 24 ] and women [ 25 ] may partly contribute to the corresponding vascular deterioration reflected by increased BHV.…”

“…Furthermore, loss of sex hormones at age 50 y in men [ 24 ] and women [ 25 ] may partly contribute to the corresponding vascular deterioration reflected by increased BHV. Anabolic hormones like sex hormone and insulin play a key role in basal bone marrow cell proliferation [ 23 , 26 ] to sustain vascular function [ 27 ].…”