Increasing age is an independent major risk factor for
the development of cardio- and cerebrovascular diseases. Due to increasing life
expectancy (Fig. 1) and constant birth rates, populations are aging. Thus, it is becoming increasingly important to
understand how aging directly affects organ function and causes disease so as
to be prepared to deal with the fast approaching problem of “global aging”.
Figure 1 Life expectancy at birth for the world and major development groups, 1950-2100. (Source: United Nations Population Division, World Population Prospects: The 2012 Revision. Highlights and Advance Tables)
This research team focuses on studying endothelial aging;
in particular, this group focuses on studying the mechanisms by which aging
affects vascular function and how these mechanisms are relevant to stroke, a
major age-related cerebrovascular disease. The main hypothesis is based on the
theory that aging and cerebrovascular disease such as stroke, occur through
similar mechanisms oftentimes involving the generation of “reactive oxygen
species” (ROS). In line with this hypothesis, several genes which mediate the
process of aging are also involved in the generation of ROS (Fig. 2).
Figure
2: The “Aging/CVD/CBVD” paradigm. Cardiovascular disease (CVD),
Cerebrovascular Disease (CBVD) and aging are mediated by similar
mechanisms which oftentimes control the production of reactive oxygen
species (ROS).
Based on the above, we studied the role of
different genes in aging as well as in stroke and by doing so could demonstrate
that mice lacking the aging gene p66Shc display a delayed onset of
age-dependent vascular dysfunction.
Furthermore, the same mice develop smaller brain lesions and showed
preserved neurological function after being exposed to an experimental model of
stroke (Fig. 3). In both studies, researchers from this team could demonstrate
that the underlying mechanism explaining the experimental data was represented
by a decreased production of ROS.
Figure 3 A: Quantification of stroke size after MCAO and 24h reperfusion in wild type and p66Shc-/- mice (n=6). B: Bederson test showing that p66Shc-/-, but not wild type, who underwent MCAO-reperfusion display a recovery in the coordination of hind and fore limbs at day 1 (n= 6; 0 = perfect coordination, 5 = no coordination).
- Publications
- Spescha RD, Shi Y, Wegener S, Keller S, Weber
B, Wyss MM, Lauinger N, Tabatabai G, Paneni F, Cosentino F, Hock C,
Weller M, Nitsch RM, Lüscher TF and Camici GG Deletion of the ageing gene p66Shc reduces early stroke size following ischaemia/reperfusion brain injury.
Eur Heart J. 2013 Jan;34(2):96-103
- Breitenstein A, Wyss CA,
Spescha RD, Franzeck FC, Hof D, Riwanto M, Hasun M, Akhmedov A, von
Eckardstein A, Maier W, Landmesser U, Lüscher TF, Camici GG
Peripheral blood monocyte sirt1 expression is reduced in patients with coronary artery disease.
PLoS One. 2013;8(1):e53106
- Shi Y, Savarese G, Perrone-Filardi P, Lüscher TF, Camici GG
Enhanced age-dependent cerebrovascular dysfunction is mediated by adaptor protein p66Shc.
Int J Cardiol. 2014 Jun 27
- Spescha RD, Glanzmann M, Simic B, Witassek F, Keller S, Akhmedov A, Tanner FC, Lüscher TF, Camici GG
Adaptor Protein p66Shc Mediates Hypertension-Associated, Cyclic Stretch-Dependent, Endothelial Damage.
Hypertension. 2014 May 19
