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Evidence for accelerated biological ageing in young adults with Prader-Willi syndrome.

OBJECTIVE: Adults with Prader-Willi syndrome (PWS) are at increased risk of developing age-associated diseases early in life and, like in premature ageing syndromes, ageing might be accelerated. We investigated leukocyte telomere length (LTL), a marker of biological age, in young adults with PWS and compared LTL to healthy young adults of similar age. As all young adults with PWS were treated with growth hormone (GH), we also compared LTL in PWS subjects to GH-treated young adults born short for gestational age (SGA).

DESIGN: Cross-sectional study in age-matched young adults; 47 with PWS, 135 healthy and 75 born SGA.

MEASUREMENTS: LTL measured by quantitative PCR, expressed as T/S ratio.

RESULTS: Median (IQR) LTL was 2.6 (2.4; 2.8) at a median (IQR) age of 19.2 (17.7; 21.3) years in PWS, 3.1 (2.9; 3.5) in healthy young adults and 3.1 (2.8; 3.4) in the SGA group. Median LTL in PWS was significantly lower compared to both control groups (p<0.01). In PWS, a lower LTL tended to be associated with a lower total IQ (r=0.35, p=0.08). There was no association between LTL and duration of GH treatment, cumulative GH dose or several risk factors for type 2 diabetes mellitus or cardiovascular disease.

CONCLUSIONS: Young adults with PWS have significantly shorter median LTL compared to age-matched healthy young adults and GH-treated young adults born SGA. The shorter telomeres might play a role in the premature ageing in PWS, independent of GH. Longitudinal research is needed to determine the influence of LTL on ageing in PWS.

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