66
that the accumulation of progerin in HGPS-iPSC derived SMCs led to a downregulation of DNA-dependent protein kinase catalytic subunit expression [63] and
poly(ADP-ribose) polymerase 1 [138], which resulted in low cell proliferation. In
addition, the use of ECs from HGPS-iPSCs showed that these cells had higher
mechanosensitivity, likely due to an elevation of channel V2 expression upon
mechanical stimulation [65]. It is expected that the combination of these HGPS
cells in bioengineered systems will facilitate the discovery of new molecular targets.
Future studies should evaluate the effect of flow shear stress in vascular cells and to
determine the mechanisms behind their mechanosensitivity.
This review also highlights a set of markers and features that characterize vascular aging, both in physiological and pathological conditions. It is known that molecular aging is controlled by multiple pathways, and their impact, as well as how they
intertwine, is not completely understood [59]. Although it is known that the ECM is
significantly altered during aging, it remains to be determined its effect in the aging
process, as well as its effects in inducing “aging” in young vascular cells. The creation of substrates with variable stiffness using recent technologies [46], as well as
the identification of new ECM molecules that mediate the aging process, might
facilitate the in vitro study of this process.
References
1. Adler, A. S., et al. (2007). Motif module map reveals enforcement of aging by continual
NF-kappaB activity. Genes & Development, 21(24), 3244–3257.
2. Aliper, A. M., Csoka, A. B., Buzdin, A., Jetka, T., Roumiantsev, S., Moskalev, A., et al.
(2015). Signaling pathway activation drift during aging: Hutchinson-Gilford progeria syndrome fibroblasts are comparable to normal middle-age and old-age cells. Aging-Us, 7(1),
26–37.
3. Armanios, M., et al. (2009). Short telomeres are sufficient to cause the degenerative defects
associated with aging. The American Journal of Human Genetics, 85(6), 823–832.
4. Atchison, L., et al. (2017). A tissue engineered blood vessel model of Hutchinson-Gilford
progeria syndrome using human iPSC-derived smooth muscle cells. Scientific Reports, 7(1),
8168.
5. Baker, D. J., et al. (2011). Clearance of p16Ink4a-positive senescent cells delays ageingassociated disorders. Nature, 479(7372), 232–236.
6. Baker, D. J., et al. (2016). Naturally occurring p16(Inks4a)-positive cells shorten healthy
lifespan. Nature, 530(7589), 184–189.
7. Baker, P. B., Baba, N., & Boesel, C. P. (1981). Cardiovascular-abnormalities in progeria case-report and review of the literature. Archives of Pathology & Laboratory Medicine,
105(7), 384–386.
8. Baratchi, S., et al. (2017). Molecular sensors of blood flow in endothelial cells. Trends in
Molecular Medicine, 23(9), 850–868.
9. Beck Jr., L., & D'Amore, P. A. (1997). Vascular development: cellular and molecular regulation. The FASEB Journal, 11(5), 365–373.
10. Bergo, M. O., et al. (2002). Zmpste24 deficiency in mice causes spontaneous bone fractures,
muscle weakness, and a prelamin A processing defect. Proceedings of the National Academy
of Sciences of the United States of America, 99(20), 13049–13054.
P. R. Pitrez et al.
that the accumulation of progerin in HGPS-iPSC derived SMCs led to a downregulation of DNA-dependent protein kinase catalytic subunit expression [63] and
poly(ADP-ribose) polymerase 1 [138], which resulted in low cell proliferation. In
addition, the use of ECs from HGPS-iPSCs showed that these cells had higher
mechanosensitivity, likely due to an elevation of channel V2 expression upon
mechanical stimulation [65]. It is expected that the combination of these HGPS
cells in bioengineered systems will facilitate the discovery of new molecular targets.
Future studies should evaluate the effect of flow shear stress in vascular cells and to
determine the mechanisms behind their mechanosensitivity.
This review also highlights a set of markers and features that characterize vascular aging, both in physiological and pathological conditions. It is known that molecular aging is controlled by multiple pathways, and their impact, as well as how they
intertwine, is not completely understood [59]. Although it is known that the ECM is
significantly altered during aging, it remains to be determined its effect in the aging
process, as well as its effects in inducing “aging” in young vascular cells. The creation of substrates with variable stiffness using recent technologies [46], as well as
the identification of new ECM molecules that mediate the aging process, might
facilitate the in vitro study of this process.
References
1. Adler, A. S., et al. (2007). Motif module map reveals enforcement of aging by continual
NF-kappaB activity. Genes & Development, 21(24), 3244–3257.
2. Aliper, A. M., Csoka, A. B., Buzdin, A., Jetka, T., Roumiantsev, S., Moskalev, A., et al.
(2015). Signaling pathway activation drift during aging: Hutchinson-Gilford progeria syndrome fibroblasts are comparable to normal middle-age and old-age cells. Aging-Us, 7(1),
26–37.
3. Armanios, M., et al. (2009). Short telomeres are sufficient to cause the degenerative defects
associated with aging. The American Journal of Human Genetics, 85(6), 823–832.
4. Atchison, L., et al. (2017). A tissue engineered blood vessel model of Hutchinson-Gilford
progeria syndrome using human iPSC-derived smooth muscle cells. Scientific Reports, 7(1),
8168.
5. Baker, D. J., et al. (2011). Clearance of p16Ink4a-positive senescent cells delays ageingassociated disorders. Nature, 479(7372), 232–236.
6. Baker, D. J., et al. (2016). Naturally occurring p16(Inks4a)-positive cells shorten healthy
lifespan. Nature, 530(7589), 184–189.
7. Baker, P. B., Baba, N., & Boesel, C. P. (1981). Cardiovascular-abnormalities in progeria case-report and review of the literature. Archives of Pathology & Laboratory Medicine,
105(7), 384–386.
8. Baratchi, S., et al. (2017). Molecular sensors of blood flow in endothelial cells. Trends in
Molecular Medicine, 23(9), 850–868.
9. Beck Jr., L., & D'Amore, P. A. (1997). Vascular development: cellular and molecular regulation. The FASEB Journal, 11(5), 365–373.
10. Bergo, M. O., et al. (2002). Zmpste24 deficiency in mice causes spontaneous bone fractures,
muscle weakness, and a prelamin A processing defect. Proceedings of the National Academy
of Sciences of the United States of America, 99(20), 13049–13054.
P. R. Pitrez et al.