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The Leiden Longevity Study: Identification of biomarkers of the rate of ageing

ABSTRACT: The aim of the study is to identify genetic mechanisms of longevity and to characterize their interaction with the environment. Using the results the future health of people without familial longevity can be improved in old age. Long-lived siblings of European descent were recruited together with their offspring and the partners of the offspring. Families were recruited if at least two long-lived siblings were alive and fulfilled the age criterion of 89 years or older for males and 91 years or older for females, representing less than 0.5% of the Dutch population in 2001.

INSTRUMENT(S): Bruker

PROVIDER: MTBLS974 | MetaboLights | 2019-07-11

REPOSITORIES: MetaboLights

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			Action	DRS
	LLS_SIBS_0_R_1_ID_1000_NMR_10.zip	Other
	LLS_SIBS_0_R_1_ID_1000_NMR_11.zip	Other
	LLS_SIBS_0_R_1_ID_1000_NMR_13.zip	Other
	LLS_SIBS_0_R_1_ID_1001_NMR_10.zip	Other
	LLS_SIBS_0_R_1_ID_1001_NMR_11.zip	Other

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Publications

Evidence of genetic enrichment for exceptional survival using a family approach: the Leiden Longevity Study.

Schoenmaker Manja M de Craen Anton J M AJ de Meijer Paul H E M PH Beekman Marian M Blauw Gerard J GJ Slagboom P Eline PE Westendorp Rudi G J RG

European journal of human genetics : EJHG 20060101 1

We conducted a sib pair study in very old subjects for the purpose of mapping longevity loci. In the present analysis, we explore whether our recruitment strategy has resulted in a population enriched for a heritable component for exceptional longevity. Our study includes families with at least two long-living siblings (men aged 89 years or above; women aged 91 years or above). Data were collected on date of birth and, if applicable, date of death of parents, brothers and sisters, offspring, and ...[more]

PMID: 16251894

Publication: 1/3

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Gene expression profiles in the Leiden Longevity Study

Project description:Biomarkers of familial longevity may represent mechanisms underlying healthy aging. To identify gene expression profiles marking human familial longevity, an explorative genome-wide expression study was performed among 50 families from the Leiden Longevity Study who have a life-long survival advantage of 30%. Gene expression profiles were compared between 50 nonagenarians (mean age 93.4 years) and 50 controls (mean age 61.9 years) to investigate differential gene expression that may arise as a function of both chronological age and familial longevity. Differential expression was observed for 2953 probes (FDR≤0.05) and for 109 GO terms, which corresponded well with previously reported findings on gene expression changes associated with chronological age, such as ‘immune response’, ‘signal transduction’ and ‘regulation of gene transcription’. To explore which of the 2953 chronological age-related probes also marked familial longevity, we compared gene expression profiles of 50 offspring of the nonagenarians (mean age 60.8 years) with the same 50 controls. Since the average gene expression levels did not differ between offspring and controls, we tested for differential expression as a function of age (age range 43-79 years). We identified 360 probes (FDR≤0.1) and the ‘Rho protein signal transduction’ GO biological process (FWER = 0.079) whose expression signatures marked familial longevity already at middle-age. Of these probes, 236 were annotated and represent 244 known genes, including WRN and MYC. Interestingly, 51 genes are involved in the regulation of gene expression. Further investigation into the genes involved may be important for unraveling mechanisms underlying longevity.

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