Intracellular signaling of the aging suppressor protein Klotho.

The Klotho protein deficiency is known to participate in premature aging. As an aging suppressor, Klotho is an important molecule in aging processes and its overexpression results in longevity. Due to many reasons, the insulin/insulin-like growth factor-1 (IGF-1) has been considered as a key pathway in aging research. The Klotho gene is closely related to this pathway. The Klotho gene encodes a transmembrane protein that after cleavage is also found as a secreted protein. Importantly, its overexpression suppresses insulin/IGF-1 signaling and thus extends the lifespan. In addition, Klotho participates in the regulation of several other intracellular signaling pathways, including regulation of FGF23 signaling, cAMP, PKC, transforming growth factor-ß (TGF-ß), p53/p21, and Wnt signaling. The aim of this review is to summarize current literature that shows the involvement of Klotho in the regulation of several intracellular pathways. The results of our review clearly indicate that Klotho participates in several intracellular signaling pathways, and by regulating them, Klotho is involved in aging and longevity.

High prevalence of major neurological disorders in two Albanian communities: results of a door-to-door survey.

BACKGROUND: There are few epidemiological studies on neurological disorders in Albania. METHODS: A door-to-door survey was undertaken in two geographical areas (Tirana and Saranda) with different socioeconomic backgrounds. Two random samples of the local population underwent a structured interview to ascertain headache, epilepsy, dementia, parkinsonism, multiple sclerosis, polyneuropathy, stroke and cerebral palsy. Each diagnosis was made using standard criteria for epidemiological studies and was confirmed by history, neurological examination and, where available, the review of personal medical records. Lifetime prevalence ratios with 95% confidence intervals were calculated. RESULTS: Of the 9,869 individuals screened (Tirana 4,953; Saranda 4,916), 4,867 were males aged 1-91 years (median 39 years) and 5,002 were females aged 1-96 years (median 37 years). Crude prevalence ratios (per 1,000) were: headache 241.9 (233.5-250.3), polyneuropathy 32.5 (29.0-36.0), epilepsy 14.2 (11.7-16.3), stroke 12.4 (10.2-14.6), dementia 9.6 (7.7-11.5), parkinsonism 8.0 (6.2-9.8), cerebral palsy 4.8 (3.4-6.2), and multiple sclerosis 0.3 (0.0-0.6). Prevalence varied with age and gender, with differences across diseases. Except for polyneuropathy (Tirana 39.8; Saranda 25.2), ratios were not different in the two study areas. CONCLUSIONS: The prevalence of selected neurological disorders in Albania is higher than in other countries. Differences may be explained by study design, population structure and/or genetic and environmental factors.