Tocotrienol-Rich Fraction Prevents Cell Cycle Arrest and Elongates Telomere Length in Senescent Human Diploid Fibroblasts

<table>Comparison of total DNA damage at various stages of cellular ageing measured by Comet assay. Damaged DNA was higher in senescent HDFs which was decreased with TRF treatment. <sup>a</sup>Denotes <svg height="11.375" id="M34" style="vertical-align:-0.1638pt" version="1.1" viewbox="0 0 50.549999 11.375" width="50.549999" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink">
<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><path d="M619 482q0 -69 -40.5 -119t-96 -72.5t-118.5 -26.5h-44l-70 20l-31 -151q-14 -67 0.5 -83t89.5 -22l-5 -28h-287l8 28q65 7 81.5 22t29.5 83l79 398q12 56 0.5 70.5t-78.5 20.5l7 28h255q108 0 164 -43t56 -125zM524 478q0 141 -146 141q-25 0 -47 -8q-16 -6 -20.5 -13.5
t-10.5 -39.5l-43 -241q37 -13 83 -13q67 0 125.5 45t58.5 129z" id="x1D443"></path></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><path d="M512 -3l-437 233v51l437 233v-58l-378 -200v-2l378 -199v-58z" id="x3C"></path></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><path d="M113 -12q-24 0 -39.5 16t-15.5 42q0 24 16 40.5t40 16.5t40 -16.5t16 -40.5q0 -26 -16 -42t-41 -16z" id="x2E"></path></g><g transform="matrix(.017,-0,0,-.017,34.162,11.112)"><path d="M241 635q53 0 94 -28.5t63.5 -76t33.5 -102.5t11 -116q0 -58 -11 -112.5t-34 -103.5t-63.5 -78.5t-94.5 -29.5t-95 28t-64.5 75t-34.5 102.5t-11 118.5q0 58 11.5 112.5t34.5 103t64.5 78t95.5 29.5zM238 602q-32 0 -55.5 -25t-35.5 -68t-17.5 -91t-5.5 -105
q0 -76 10 -138.5t37 -107.5t69 -45q32 0 55.5 25t35.5 68.5t17.5 91.5t5.5 105t-5.5 105.5t-18 92t-36 68t-56.5 24.5z" id="x30"></path></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><path d="M153 550l-26 -186q79 31 111 31q90 0 141.5 -51t51.5 -119q0 -93 -89 -166q-85 -69 -173 -71q-32 0 -61.5 11.5t-41.5 23.5q-18 17 -17 34q2 16 22 33q14 9 26 -1q61 -50 124 -50q60 0 93 43.5t33 104.5q0 69 -41.5 110t-121.5 41q-53 0 -102 -20l38 305h286l6 -8
l-26 -65h-233z" id="x35"></path></g>
</svg> compared to untreated young HDFs, <svg height="20.8375" id="M35" style="vertical-align:-3.27605pt" version="1.1" viewbox="0 0 60.049999 20.8375" width="60.049999" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink">
<g transform="matrix(.012,-0,0,-.012,2.9,8.537)"><path d="M152 404l81 35q23 10 41 10q81 0 139 -61.5t58 -149.5q0 -107 -74.5 -178.5t-176.5 -71.5q-71 0 -147 36v555q0 48 -9.5 59.5t-56.5 15.5v23q79 10 145 35v-308zM152 374v-258q0 -20 6 -35q7 -19 30 -37t58 -18q63 0 99.5 50t36.5 137q0 82 -43.5 131t-108.5 49
q-44 0 -78 -19z" id="x62"></path></g>
<g transform="matrix(.017,-0,0,-.017,9.563,17.888)"><path d="M619 482q0 -69 -40.5 -119t-96 -72.5t-118.5 -26.5h-44l-70 20l-31 -151q-14 -67 0.5 -83t89.5 -22l-5 -28h-287l8 28q65 7 81.5 22t29.5 83l79 398q12 56 0.5 70.5t-78.5 20.5l7 28h255q108 0 164 -43t56 -125zM524 478q0 141 -146 141q-25 0 -47 -8q-16 -6 -20.5 -13.5
t-10.5 -39.5l-43 -241q37 -13 83 -13q67 0 125.5 45t58.5 129z" id="x1D443"></path></g><g transform="matrix(.017,-0,0,-.017,25.1,16.7)"><path d="M512 -3l-437 233v51l437 233v-58l-378 -200v-2l378 -199v-58z" id="x3C"></path></g><g transform="matrix(.017,-0,0,-.017,39.787,16.7)"><path d="M113 -12q-24 0 -39.5 16t-15.5 42q0 24 16 40.5t40 16.5t40 -16.5t16 -40.5q0 -26 -16 -42t-41 -16z" id="x2E"></path></g><g transform="matrix(.017,-0,0,-.017,43.663,16.7)"><path d="M241 635q53 0 94 -28.5t63.5 -76t33.5 -102.5t11 -116q0 -58 -11 -112.5t-34 -103.5t-63.5 -78.5t-94.5 -29.5t-95 28t-64.5 75t-34.5 102.5t-11 118.5q0 58 11.5 112.5t34.5 103t64.5 78t95.5 29.5zM238 602q-32 0 -55.5 -25t-35.5 -68t-17.5 -91t-5.5 -105
q0 -76 10 -138.5t37 -107.5t69 -45q32 0 55.5 25t35.5 68.5t17.5 91.5t5.5 105t-5.5 105.5t-18 92t-36 68t-56.5 24.5z" id="x30"></path></g><g transform="matrix(.017,-0,0,-.017,51.822,16.7)"><path d="M153 550l-26 -186q79 31 111 31q90 0 141.5 -51t51.5 -119q0 -93 -89 -166q-85 -69 -173 -71q-32 0 -61.5 11.5t-41.5 23.5q-18 17 -17 34q2 16 22 33q14 9 26 -1q61 -50 124 -50q60 0 93 43.5t33 104.5q0 69 -41.5 110t-121.5 41q-53 0 -102 -20l38 305h286l6 -8
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</svg> compared to untreated presenescent HDFs, <svg height="17.7125" id="M36" style="vertical-align:-3.27605pt" version="1.1" viewbox="0 0 59.037498 17.7125" width="59.037498" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink">
<g transform="matrix(.012,-0,0,-.012,2.9,5.4)"><path d="M390 111l17 -21q-34 -45 -80 -73.5t-89 -28.5q-91 0 -146 62t-55 147q0 118 101 195q74 57 149 57h1q59 0 90 -27q16 -14 16 -30q0 -15 -12 -29t-21 -14q-8 0 -19 11q-44 41 -101 41q-52 0 -87.5 -42.5t-35.5 -117.5q0 -49 15 -87t39 -58t49 -30t48 -10q33 0 60.5 12
t60.5 43z" id="x63"></path></g>
<g transform="matrix(.017,-0,0,-.017,8.55,14.75)"><path d="M619 482q0 -69 -40.5 -119t-96 -72.5t-118.5 -26.5h-44l-70 20l-31 -151q-14 -67 0.5 -83t89.5 -22l-5 -28h-287l8 28q65 7 81.5 22t29.5 83l79 398q12 56 0.5 70.5t-78.5 20.5l7 28h255q108 0 164 -43t56 -125zM524 478q0 141 -146 141q-25 0 -47 -8q-16 -6 -20.5 -13.5
t-10.5 -39.5l-43 -241q37 -13 83 -13q67 0 125.5 45t58.5 129z" id="x1D443"></path></g><g transform="matrix(.017,-0,0,-.017,24.088,13.563)"><path d="M512 -3l-437 233v51l437 233v-58l-378 -200v-2l378 -199v-58z" id="x3C"></path></g><g transform="matrix(.017,-0,0,-.017,38.774,13.563)"><path d="M113 -12q-24 0 -39.5 16t-15.5 42q0 24 16 40.5t40 16.5t40 -16.5t16 -40.5q0 -26 -16 -42t-41 -16z" id="x2E"></path></g><g transform="matrix(.017,-0,0,-.017,42.65,13.563)"><path d="M241 635q53 0 94 -28.5t63.5 -76t33.5 -102.5t11 -116q0 -58 -11 -112.5t-34 -103.5t-63.5 -78.5t-94.5 -29.5t-95 28t-64.5 75t-34.5 102.5t-11 118.5q0 58 11.5 112.5t34.5 103t64.5 78t95.5 29.5zM238 602q-32 0 -55.5 -25t-35.5 -68t-17.5 -91t-5.5 -105
q0 -76 10 -138.5t37 -107.5t69 -45q32 0 55.5 25t35.5 68.5t17.5 91.5t5.5 105t-5.5 105.5t-18 92t-36 68t-56.5 24.5z" id="x30"></path></g><g transform="matrix(.017,-0,0,-.017,50.81,13.563)"><path d="M153 550l-26 -186q79 31 111 31q90 0 141.5 -51t51.5 -119q0 -93 -89 -166q-85 -69 -173 -71q-32 0 -61.5 11.5t-41.5 23.5q-18 17 -17 34q2 16 22 33q14 9 26 -1q61 -50 124 -50q60 0 93 43.5t33 104.5q0 69 -41.5 110t-121.5 41q-53 0 -102 -20l38 305h286l6 -8
l-26 -65h-233z" id="x35"></path></g>
</svg> compared to untreated senescent HDFs, <svg height="20.8375" id="M37" style="vertical-align:-3.27605pt" version="1.1" viewbox="0 0 60.287498 20.8375" width="60.287498" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink">
<g transform="matrix(.012,-0,0,-.012,2.9,8.537)"><path d="M517 51v-25q-101 -18 -155 -38v65l-61 -36q-50 -29 -78 -29q-68 0 -126.5 58t-58.5 155q0 103 77 175.5t180 72.5q36 0 67 -12v143q0 48 -11.5 58.5t-65.5 14.5v25q79 9 156 34v-597q0 -38 7.5 -48t36.5 -13zM362 85v275q-35 51 -103 51q-20 0 -40.5 -8.5t-42 -28
t-35 -57.5t-13.5 -89q0 -83 42 -130t96 -47q51 0 96 34z" id="x64"></path></g>
<g transform="matrix(.017,-0,0,-.017,9.8,17.888)"><path d="M619 482q0 -69 -40.5 -119t-96 -72.5t-118.5 -26.5h-44l-70 20l-31 -151q-14 -67 0.5 -83t89.5 -22l-5 -28h-287l8 28q65 7 81.5 22t29.5 83l79 398q12 56 0.5 70.5t-78.5 20.5l7 28h255q108 0 164 -43t56 -125zM524 478q0 141 -146 141q-25 0 -47 -8q-16 -6 -20.5 -13.5
t-10.5 -39.5l-43 -241q37 -13 83 -13q67 0 125.5 45t58.5 129z" id="x1D443"></path></g><g transform="matrix(.017,-0,0,-.017,25.338,16.7)"><path d="M512 -3l-437 233v51l437 233v-58l-378 -200v-2l378 -199v-58z" id="x3C"></path></g><g transform="matrix(.017,-0,0,-.017,40.024,16.7)"><path d="M113 -12q-24 0 -39.5 16t-15.5 42q0 24 16 40.5t40 16.5t40 -16.5t16 -40.5q0 -26 -16 -42t-41 -16z" id="x2E"></path></g><g transform="matrix(.017,-0,0,-.017,43.9,16.7)"><path d="M241 635q53 0 94 -28.5t63.5 -76t33.5 -102.5t11 -116q0 -58 -11 -112.5t-34 -103.5t-63.5 -78.5t-94.5 -29.5t-95 28t-64.5 75t-34.5 102.5t-11 118.5q0 58 11.5 112.5t34.5 103t64.5 78t95.5 29.5zM238 602q-32 0 -55.5 -25t-35.5 -68t-17.5 -91t-5.5 -105
q0 -76 10 -138.5t37 -107.5t69 -45q32 0 55.5 25t35.5 68.5t17.5 91.5t5.5 105t-5.5 105.5t-18 92t-36 68t-56.5 24.5z" id="x30"></path></g><g transform="matrix(.017,-0,0,-.017,52.06,16.7)"><path d="M153 550l-26 -186q79 31 111 31q90 0 141.5 -51t51.5 -119q0 -93 -89 -166q-85 -69 -173 -71q-32 0 -61.5 11.5t-41.5 23.5q-18 17 -17 34q2 16 22 33q14 9 26 -1q61 -50 124 -50q60 0 93 43.5t33 104.5q0 69 -41.5 110t-121.5 41q-53 0 -102 -20l38 305h286l6 -8
l-26 -65h-233z" id="x35"></path></g>
</svg> compared to TRF-treated young HDFs. Data are presented as mean ± SD, <svg height="11.225" id="M38" style="vertical-align:-0.1638pt" version="1.1" viewbox="0 0 36.237499 11.225" width="36.237499" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink">
<g transform="matrix(.017,-0,0,-.017,.062,10.963)"><path d="M495 86q-46 -47 -87 -72.5t-63 -25.5q-43 0 -16 107l49 210q7 34 8 50.5t-3 21t-13 4.5q-35 0 -109.5 -72.5t-115.5 -140.5q-21 -75 -38 -159q-50 -10 -76 -21l-6 8l84 340q8 35 -4 35q-17 0 -67 -46l-15 26q44 44 85.5 70.5t64.5 26.5q35 0 10 -103l-24 -98h2
q42 56 97 103.5t96 71.5q46 26 74 26q9 0 16 -2.5t14 -11.5t9.5 -24.5t-1 -44t-13.5 -68.5q-30 -117 -47 -200q-4 -19 -3.5 -25t6.5 -6q21 0 70 48z" id="x1D45B"></path></g><g transform="matrix(.017,-0,0,-.017,13.305,10.963)"><path d="M535 323h-483v50h483v-50zM535 138h-483v50h483v-50z" id="x3D"></path></g><g transform="matrix(.017,-0,0,-.017,28.008,10.963)"><path d="M137 343l67 33q37 17 63 17q79 0 129.5 -53t50.5 -131q0 -92 -58 -156.5t-147 -64.5t-147 68t-58 182q0 63 17 119t43 95.5t61.5 72t69 52t67.5 31.5q62 22 128 33l6 -32q-56 -11 -108 -35q-149 -71 -184 -231zM227 337q-47 0 -95 -27q-6 -23 -6 -70q0 -93 36 -155.5
t96 -62.5q53 0 78 45.5t25 105.5q0 68 -35 116t-99 48z" id="x36"></path></g>
</svg>.</table>

BioMed Research International

fig5

Figure 5

Figure 5: Tocotrienol-Rich Fraction Prevents Cell Cycle Arrest and Elongates Telomere Length in Senescent Human Diploid Fibroblasts 