Molecular remodeling of potassium channels in fibroblasts from centenarians: A marker of longevity?

作者：Zironi Isabella; Gaibani Paolo; Remondini Daniel; Salvioli Stefano; Altilia Serena; Pierini Michela; Aicardi Giorgio; Verondini Ettore; Milanesi Luciano; Bersani Ferdinando; Gravina Silvia; Roninson Igor B; Franceschi Claudio; Castellani Gastone^*

来源：Mechanisms of Ageing and Development, 2010, 131(11-12): 674-681.

DOI：10.1016/j.mad.2010.09.004

• Human aging and longevity
• Membrane currents
• Patch-clamp
• Voltage-gated Kv1.1
• BKCa channels

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 beta 1 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.

• 出版日期2010-12