Investigation On The Buccal Telomere Length For The Zhuang Long-Lived Families From Guangxi Bamaarea

Background:Telomere is a unique DNA-protein complex which caps the end of chromosome and protects it from end-to-end fusing. It has been clear that the telomere length (TL) of normal somatic cells shortens with increasing proliferation in vitro due to the so-called "end replication problem" and loses its DNA protective effect and triggers replicative senescence. However, the aging process and its underlying mechanism of somatic cells in vivo may be much more complicated, in which the telomere shortening model, its mechanism of shortening and the role it play in cellular senescence of telomere are far from unknown. Oral mucosal exfoliated cell (OMEC) is commonly used in aging research because it is an in vivo somatic cell which is ready to collect and its senescence can reflect the aging process of the body to some extent. Bama area in Guangxi Province has emerged as an aging/longevity research base over the past decades due to its large population of long-lived individuals.Objective: The main purposes of the current study are:to investigate the telomere dynamics of OMEC with increasing age, its possible hereditary tendency, and the role it may play in the longevity in Bama long-lived families (BLF); to investigate the possible hereditary pattern and the heritability of OTL in BLF; to investigate the possible correlation between OTL and leucocyte telomere length (LTL).Methods:1. Study group:BLF, a lineage includes one or more individual with exceptional longevity whose age is90or above, n=1059, mean age±SD,55.47±28.78. Control groups, include three lineages, one is in Bama area without a familial history of exceptional longevity (Bama non-long-lived families, BNLF), two are in Pingguo, a county, about150km from Bama area, Pingguo long-lived families (PLF) and Pingguo non-long-lived familes (PNLF), which is with or without a familial history of exceptional longevity, respectively. The number of family member and the mean age of each control group are: BNLF, n=263, age=44.43±27.07; PLF, n=298, age=50.17±30.53; PNLF, n=417,age=39.19±25.29.2. Real-time quantitative PCR (qRT-PCR) was employed to determine the OTL of each group, and comparison of OTL was performed among groups. The heritability of OTL was calculated and its hereditary pattern was evaluated across generations.3. qRT-PCR was also employed to determine the LTL of each group and LTL was compared with OTL to explore their potential correlation.Results:1. Both OTL and LTL were inversely correlated with increasing age in BLF and other control families, i.e. the older of the individual’s age, the shorter of the individual’s TL. This trend is independent of sex.2. The OTL in BLF was significantly longer than that of BNLF and PLF, especially in60-89years subgroup. In addition, the percentage of the4th quartile of OTL, which represents the proportion of the longest OTL, in BLF was greater than that of other families.3. The OTL in males in BLF and PNLF but not in other families were significantly longer than were females. But this difference did not exist after gender and age stratification. Similar tendency was found in LTL.4. The LTL in BLF was also longer than that of PLF. This significance did not change in the overall population, in age subgroups of≥90,60-89,40-64, and15-39, and in parental, grandchildren, and the fourth generation subgroups. Similarly as OTL, the percentage of the4th quartile of LTL in BLF was greater than that of other families.5. OTL was maternally inherited in BLF with a heritability of82%. The OTL of the younger generations was found to be related with their parental OTL in other families, but no distinct parental or maternal hereditary model was displayed in these families. The maternal heredity was also found to run in the overall population, especially in the4th and1st quartiles.6. The heredity of LTL in BLF (heritability86%) and in combined families but not in other control groups displayed both maternal and paternal models, particularly in the4th and1st quartiles.7. OTL is longer than LTL in all families studied.8. OTL is positively correlated with LTL in all families studied.Conclusions: 1. OTL and LTL are inversely correlated with age, that is, OTL and LTL shorten with increasing age.2. OTL is longer than LTL in all families studied and OTL is positively correlated with LTL.3. The telomere length,4th and the1st quartile in particular, of buccal cell and leukocytes of the offspring of BLF are evidently influenced by that of their parents, exhibiting a maternal or paternal genetic model.4. Taken together, these findings suggest that higher heredity of OTL and LTL is running in BLF, which may in part explain the longevity of Bama area.