TY - JOUR
T1 - Influences of circulatory factors on intervertebral disc aging phenotype
AU - Lei, Changbin
AU - Colangelo, Debora
AU - Patil, Prashanti
AU - Li, Vivian
AU - Ngo, Kevin
AU - Wang, Dong
AU - Dong, Qing
AU - Yousefzadeh, Matthew J.
AU - Lin, Hongsheng
AU - Lee, Joon
AU - Kang, James
AU - Sowa, Gwendolyn
AU - Wyss-Coray, Tony
AU - Niedernhofer, Laura J.
AU - Robbins, Paul D.
AU - Huffman, Derek M.
AU - Vo, Nam
N1 - Publisher Copyright:
© Lei et al.
PY - 2020/6/30
Y1 - 2020/6/30
N2 - Whether disc aging is influenced by factors beyond its local environment is an important unresolved question. Here we performed heterochronic parabiosis in mice to study the effects of circulating factors in young and old blood on age-associated intervertebral disc degeneration. Compared to young isochronic pairs (Y-Y), young mice paired with old mice (Y-O) showed significant increases in levels of disc MMP-13 and ADAMTS4, aggrecan fragmentation, and histologic tissue degeneration, but negligible changes in cellular senescence markers (p16INK4a, p21Cip1). Compared to old isochronic pairs (O-O), old mice paired with young mice (O-Y) exhibited a significant decrease in expression of cellular senescence markers (p16, p21, p53), but only marginal decreases in the levels of disc MMP-13 and ADAMTS4, aggrecan fragmentation, and histologic degeneration. Thus, exposing old mice to young blood circulation greatly suppressed disc cellular senescence, but only slightly decreased disc matrix imbalance and degeneration. Conversely, exposing young mice to old blood accelerated their disc matrix imbalance and tissue degeneration, with little effects on disc cellular senescence. Thus, non-cell autonomous effects of circulating factors on disc cellular senescence and matrix homeostasis are complex and suggest that disc matrix homeostasis is modulated by systemic factors and not solely through local disc cellular senescence.
AB - Whether disc aging is influenced by factors beyond its local environment is an important unresolved question. Here we performed heterochronic parabiosis in mice to study the effects of circulating factors in young and old blood on age-associated intervertebral disc degeneration. Compared to young isochronic pairs (Y-Y), young mice paired with old mice (Y-O) showed significant increases in levels of disc MMP-13 and ADAMTS4, aggrecan fragmentation, and histologic tissue degeneration, but negligible changes in cellular senescence markers (p16INK4a, p21Cip1). Compared to old isochronic pairs (O-O), old mice paired with young mice (O-Y) exhibited a significant decrease in expression of cellular senescence markers (p16, p21, p53), but only marginal decreases in the levels of disc MMP-13 and ADAMTS4, aggrecan fragmentation, and histologic degeneration. Thus, exposing old mice to young blood circulation greatly suppressed disc cellular senescence, but only slightly decreased disc matrix imbalance and degeneration. Conversely, exposing young mice to old blood accelerated their disc matrix imbalance and tissue degeneration, with little effects on disc cellular senescence. Thus, non-cell autonomous effects of circulating factors on disc cellular senescence and matrix homeostasis are complex and suggest that disc matrix homeostasis is modulated by systemic factors and not solely through local disc cellular senescence.
KW - Aging
KW - Heterochronic parabiosis
KW - Intervertebral disc
KW - Proteoglycan
KW - Systemic factors
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U2 - 10.18632/aging.103421
DO - 10.18632/aging.103421
M3 - Article
C2 - 32527988
AN - SCOPUS:85087378938
SN - 1945-4589
VL - 12
SP - 12285
EP - 12304
JO - Aging
JF - Aging
IS - 12
ER -