Lipoprotein particle profiles mark familial and sporadic human longevity.
BACKGROUND
Genetic and biochemical studies have indicated an important role for lipid metabolism in human longevity. Ashkenazi Jewish centenarians and their offspring have large low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles as compared with control individuals. This profile also coincided with a lower prevalence of disease. Here, we investigate whether this observation can be confirmed for familial longevity in an outbred European population and whether it can be extended to sporadic longevity in the general population.


RESULTS
NMR-measured lipoprotein profiles were analyzed in 165 families from the Leiden Longevity Study, consisting of 340 long-lived siblings (females >91 y, males >89 y), 511 of their offspring, and 243 partners of the offspring. Offspring had larger (21.3 versus 21.1 nm; p = 0.020) and fewer (1,470 versus 1,561 nmol/l; p = 0.011) LDL particles than their same-aged partners. This effect was even more prominent in the long-lived siblings (p < 10(-3)) and could be pinpointed to a reduction specifically in the concentration of small LDL particles. No differences were observed for HDL particle phenotypes. The mean LDL particle sizes in 259 90-y-old singletons from a population-based study were similar to those in the long-lived siblings and thus significantly larger than in partners of the offspring, suggesting that the relevance of this phenotype extends beyond familial longevity. A low concentration of small LDL particles was associated with better overall health among both long-lived siblings (p = 0.003) and 90-y-old singletons (p = 0.007).


CONCLUSIONS
Our study indicates that LDL particle profiles mark both familial and sporadic human longevity already in middle age.
Heijmans
Bastiaan T
BT
Department of Molecular Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands. b.t.heijmans@lumc.nl
Beekman
Marian
M
Houwing-Duistermaat
Jeanine J
JJ
Cobain
Mark R
MR
Powell
Jonathan
J
Blauw
Gerard Jan
GJ
van der Ouderaa
Frans
F
Westendorp
Rudi G J
RG
Slagboom
P Eline
PE
D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood*; D008136:Longevity / Q000502:physiology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010316:Particle Size; D044465:White People
D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL