Reduction of senescence‐associated beta‐galactosidase activity by vitamin E in human fibroblasts depends on subjects’ age and cell passage number

Abstract

Cell senescence is due to the permanent cell cycle arrest that occurs as a result of the inherent limited replicative capacity toward the Hayflick limit (replicative senescence), or in response to various stressors (stress‐induced premature senescence, SIPS). With the acquisition of the senescence‐associated secretory phenotype (SASP), cells release several molecules (cytokines, proteases, lipids), and express the senescence‐associated beta‐galactosidase (SA‐β‐Gal). Here we tested whether vitamin E affects SA‐β‐Gal in an in vitro model of cell ageing. Skin fibroblasts from human subjects of different age (1, 13, 29, 59, and 88 years old) were cultured until they reached replicative senescence. At different passages (Passages 2, 9, 13, and 16), these cells were treated with vitamin E for 24 hr. Vitamin E reduced SA‐β‐Gal in all cells at passage 16, but at earlier passage numbers it reduced SA‐β‐Gal only in cells isolated from the oldest subjects. Therefore, short time treatment with vitamin E decreases SA‐β‐Gal in cells both from young and old subjects when reaching replicative senescence; but in cells isolated from older subjects, a decrease in SA‐β‐Gal by vitamin E occurs also at earlier passage numbers. The possible role of downregulation of CD36 by vitamin E, a scavenger receptor essential for initiation of senescence and SASP, is discussed.

miR-146a impedes the anti-aging effect of AMPK via NAMPT suppression and NAD+/SIRT inactivation

“… 45 For replicative senescence induction, human sphenoid sinus mucosa fibroblasts were split 1:3 for passaging until they reached senescent growth arrest and replicative senescence. As reported, primary fibroblasts from 59 aged human skin tissues induced replicative senescence at passage number 16, 46 and we established replicative senescence at passage numbers 14 or 16.…”

α-Tocopherol Acetate Attenuates Mitochondrial Oxygen Consumption and Maintains Primitive Cells within Mesenchymal Stromal Cell Population

“…Also, the data presented in this paper argues that this effect is not related to an anti-oxidant function of α-TOA. It is interesting to note that the most recent data points to reduction of replicative senescence of human skin fibroblasts by tocopherol via reduction of senescence-associated beta-galactosidase [24].…”

Modulation of CD36‐mediated lipid accumulation and senescence by vitamin E analogs in monocytes and macrophages

“…(B) Defective lipid transport and lipid accumulation due to mutations in LTPs is at the basis of a number of congenital and degenerative diseases, such as ataxia with vitamin E deficiency (AVED), Niemann-Pick disease, and atherosclerotic foam cell formation. 82 By facilitating the transport and exchange of lipids, chemical lipid transporters such as αTP/βCD and related complexes may be a way to increase delivery of intact αTP, to assist and overcome defective LTP functions and to liberate trapped lipids for distribution in the body as substrates for enzymes and as components of specific membrane domains (lipid rafts, vesicles, and organelles) lysosomes 64,66,101 and is expressed in monocytes and stimulated by immune stimuli such as IL-4 and IL-13. 102,103 Mechanistically, the observed reduction of SA-βGal activity upon treatment with αTP and αTP/βCD was likely due to a marked pH increase in lysosomes.…”

“…63,64 CD36 up-regulation is important in initiating the senescence-associated secretory phenotype (SASP), activating the Src/p38/NFκB pathway and senescence-associated β-galactosidase expression (SAβ-Gal), events that could be modulated by vitamin E possibly involving its transport to the endo-lysosomal compartment. 63,65,66 Therefore, we have measured whether treatment of THP-1 monocytes and macrophages with αT, αTP, αTP/βCD, and βCD can affect cellular senescence by measuring SA-β-Gal activity. 44 Interestingly, after treatment with αTP and αTP/βCD, a reduction of SA-βGal was observed possibly reflecting the more pronounced inhibition of CD36 and the increased transport to endolysosomes of these compounds (Figure 4A,B).…”