Monday, March 12, 2012

Height Growth Genes and Aging

LSJL age related genes altered:


Genes and gene expression modules associated with caloric restriction and aging in the laboratory mouse.

"[Caloric Restriction] increased expression of Tsc22d3{downregulated by LSJL}, Zbtb16, BC055107, Sult1a1, Per1, Timp3, S3-12, Pnpla2, Ppargc1a and Cp, as well as decreased expression of Ifitm3{downregulated by LSJL}, Lasp1, Tia1, 5830428H23Rik, Hsp90b1, Hist1h2bc, Cxcl12, Col6a2{downregulated by LSJL} and Dock4{downregulated by LSJL}"

"CR increased expression of genes encoding the anti-oxidant metallothioneins (Mt1{upregulated in LSJL} and Mt2{upregulated in LSJL}), the NF-κB inhibitor IκBα (Nfkbia), as well as the tumor suppressor P21 (Cdkn1a)"

"CR increased expression of phosphatase and tensin homolog (Pten), which is a tumor suppressor that inhibits IGF-1 signals by preventing activation of the PI3K/Akt signaling pathway"

CR upregulated Sgk1 which is upregulated when the PI3K pathway is inhibited.  Surprisingly, Sgk is upregulated in LSJL.  It should be noted that no caloric restriction analysis was done specifically on the bone, bone marrow, or cartilage.

It should be remembered that mice do have complete growth plate resorption that occurs in humans.

Notable genes upregulated by aging in bone marrow:
Anxa3{downregulated in LSJL}

Notable genes downregulated by aging in bone marrow:
Vim{Upregulated by LSJL}

Age-Related Changes of Chondrogenic Growth Factors in Platelet-Rich Plasma

"PRP[Platelet-Rich Plasma] contains many growth factors that play critical roles in chondrogenesis, including insulin-like growth factor 1 (IGF-1), human growth hormone, transforming growth factor beta 1, basic fibroblast growth factor, and bone morphogenetic proteins 2, 4, and 7. PRP was isolated from 40 healthy volunteers between 20 and 60 years of age, and concentrations of bone morphogenetic proteins 2 and 4, basic fibroblast growth factor, human growth hormone, IGF-1, insulin-like growth factor-binding proteins 2 and 3, platelet-derived growth factor BB (PDGF-BB), transforming growth factor beta 1, and vascular endothelial growth factor were analyzed by enzyme-linked immunosorbent assay. Significant differences with respect to age were detected between subjects less than 30 and >30 years of age for PDGF-BB, insulin-like growth factor-binding protein 3, and IGF-1. A significant difference was also detected between subjects <40 and >40 years of age for PDGF-BB. Concentrations of other growth factors did not vary significantly across age-groups, suggesting that the molecular contents of PRP are similar for patients aged 20-60 years."

"BMP-7 [levels decline] throughout the human aging process"

"Accumulation of cartilage matrix by micromass cultures in vitro is stimulated by IGF-1 but inhibited by IGFBP-2. Elevated expression of IGFBP-3 inhibits the effects of IGF-1 and decreases proteoglycan synthesis. Increased IGFBP-3 levels are associated with degenerative cartilage diseases, induction of mesenchymal stem cell apoptosis, and antagonism of TGF-β1 chondroinductive effects in chondroprogenitor cells."

"PRP contains large quantities of IGFBP-3 (mean concentration 451 ng/mL); however, the mean concentration decreased significantly in patients older than 30 years of age (20-30 age-group = 752 ng/mL vs >30 years age-group = 350 ng/mL), suggesting that the antichondrogenic effect of IGFBP-3 may decrease during the later decades of life."

"PDGF-BB is secreted from platelet α-granules and is a major mitogenic factor for mesenchymal cells. PDGF-BB stimulates collagen synthesis and plays a role in redifferentiation of the autologous dedifferentiated chondrocytes toward chondrogenic lineage."

" The mean PDGF-BB concentration of 39.5 ng/mL in the 20-30 age-group significantly decreased to 24.9 ng/mL among all other groups. However, effective concentrations of PDGF-BB have historically varied from 4.7 to 300 ng/mL in vitro, with many studies reporting [chondroinduction] effects with concentrations below 40 ng/mL"

"In our study, the mean value of bFGF over all age-groups was 6.3 ng/mL. Previous studies illustrate that a concentration of 1 ng/mL of bFGF increased the potential for the chondrogenic differentiation of hBMSCs after 15 days in culture."

"The mean concentration [of TGF-B1] we were able to detect throughout all age-groups in our study was 54.7 ng/mL. Doses between 0.3 and 20.0 ng/mL stimulated in vitro chondrogenesis of mesenchymal cells."

"this investigation detected an average of 285 pg/mL (BMP-2) and 277 pg/mL (BMP-4) across all ages, with no significant difference among age-groups. Although our results show consistently elevated levels of BMP-2 and BMP-4, chondrogenic differentiation media typically contains 50-100 ng/mL BMP-2, suggesting that either BMP-2 is not present in sufficient concentration for chondroinduction in PRP or that picogram doses have not been adequately studied."

So older platelet rich plasma may be better for chondroinduction due to lower IGFBP-3 levels.  PRP contains sufficient levels of PDGF-BB, bFGF, and TGF-B1 for chondroinduction but not sufficient levels of BMP-2 and BMP-4.

Generating platelet rich plasma involves increasing the concentration of platelets by five-fold.  Platelet rich plasma injections are legal but can only be done by doctors.

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