TY - JOUR
T1 - Molecular remodeling of potassium channels in fibroblasts from centenarians
T2 - A marker of longevity?
AU - Zironi, Isabella
AU - Gaibani, Paolo
AU - Remondini, Daniel
AU - Salvioli, Stefano
AU - Altilia, Serena
AU - Pierini, Michela
AU - Aicardi, Giorgio
AU - Verondini, Ettore
AU - Milanesi, Luciano
AU - Bersani, Ferdinando
AU - Gravina, Silvia
AU - Roninson, Igor B.
AU - Franceschi, Claudio
AU - Castellani, Gastone
N1 - Funding Information:
This work was supported by: Fondazione del Monte Grant to GCC, EU (European Union) Grant “PROTEOMAGE” Contract no. FP6-518230 to CF; Italian Ministry of University and Research (MiUR) PRIN 2007 Project to GCC and PG; University of Bologna Grant “Ricerca Fondamentale Orientata (RFO ex 60%) 2007” to CF and SS, Roberto and Cornelia Pallotti Legacy for Cancer Research Grants to CF and SS. University of Bologna “Progetti Strategici” 2006 grant (“p53 e patologie non neoplastiche nell’anziano: uno studio multidisciplinare sul ruolo del polimorfismo al codone 72 del gene TP53”) to SS and DR.
PY - 2010/11
Y1 - 2010/11
N2 - Aging is a complex process resulting from, among other, dynamic non-linear interactions between genetics and environment. Centenarians are the best example of successful aging in humans, as they escaped from, or largely postponed, major age-related diseases. Ionic fluxes changes play a key role in several patho-physiological cellular processes, but their relation to human aging is largely unexplored. In the present study we have compared patch-clamp potassium (K+) current recordings from dermal fibroblasts (DF) obtained from young, elderly and centenarian donors. We found that in DF from elderly donors, but not from centenarians, K+ current amplitude is significantly smaller with respect to DF from young donors. Moreover, cell membrane capacitance of DF from elderly donors is smaller with respect to young donors and centenarians. We also observed that the voltage-gated Shaker Kv1.1 channel is expressed in higher percentage of elderly's and centenarian's DF than young's, whereas the large-conductance calcium-activated K+ (BKCa) channel β1 subunit is expressed in lower percentage of centenarian's DF than in elderly's and young's. The maintenance of young K+ currents and the peculiar age-related remodeling of K+ channel subtypes in centenarian's DF is likely associated with successful aging and might provide a predictive marker of longevity.
AB - Aging is a complex process resulting from, among other, dynamic non-linear interactions between genetics and environment. Centenarians are the best example of successful aging in humans, as they escaped from, or largely postponed, major age-related diseases. Ionic fluxes changes play a key role in several patho-physiological cellular processes, but their relation to human aging is largely unexplored. In the present study we have compared patch-clamp potassium (K+) current recordings from dermal fibroblasts (DF) obtained from young, elderly and centenarian donors. We found that in DF from elderly donors, but not from centenarians, K+ current amplitude is significantly smaller with respect to DF from young donors. Moreover, cell membrane capacitance of DF from elderly donors is smaller with respect to young donors and centenarians. We also observed that the voltage-gated Shaker Kv1.1 channel is expressed in higher percentage of elderly's and centenarian's DF than young's, whereas the large-conductance calcium-activated K+ (BKCa) channel β1 subunit is expressed in lower percentage of centenarian's DF than in elderly's and young's. The maintenance of young K+ currents and the peculiar age-related remodeling of K+ channel subtypes in centenarian's DF is likely associated with successful aging and might provide a predictive marker of longevity.
KW - BK channels
KW - Human aging and longevity
KW - Membrane currents
KW - Patch-clamp
KW - Voltage-gated Kv1.1
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U2 - 10.1016/j.mad.2010.09.004
DO - 10.1016/j.mad.2010.09.004
M3 - Article
C2 - 20858515
AN - SCOPUS:78649904628
SN - 0047-6374
VL - 131
SP - 674
EP - 681
JO - Mechanisms of Ageing and Development
JF - Mechanisms of Ageing and Development
IS - 11-12
ER -
