Differences in the frequencies of mtDNA haplogroups and hap- logroup clusters between the populations were evaluated by using the exact test of population differentiation (Rousset and Raymond 1995) as implemented in ARLEQUIN 2.0 (Schneider et al. 2000) or, if applicable, by the χ2 test or Fisher’s exact test.

ity in the Finnish population (Finnilä et al. 2001). A clear West Eurasian pattern of polymorphisms has been de- tected and the frequency of the haplogroups is similar to that among other Europeans, with the exception of hap- logroup U, which is more frequent than elsewhere in Eu- rope (Finnilä et al. 2000; Meinilä et al. 2001). Interest- ingly, however, significant geographical differences in mtDNA haplogroup frequencies have been detected, even within the Finnish population (Meinilä et al. 2001). The proposed role of mtDNA in longevity has been based on differences in haplogroup frequencies between centenari- ans and controls. However, as the frequencies of mtDNA haplogroups vary between ethnic groups, and even within the same group depending on the geographical origins of the individuals, both the subjects under study and their controls should be collected from the same geographical region in order to be able to compare haplogroup frequen- cies reliably. We therefore set out to study mtDNA hap- logroup frequencies among persons who had reached the age of 90 years and among middle-aged controls ascer- tained from a defined geographical region in Finland.

Results

Frequencies of mtDNA haplogroups among Vitality 90+ cases and

MtDNA haplogroups were determined in 882 samples in- cluding 225 from the Vitality 90+ group, 400 from healthy controls and 257 from infants. All the samples ex- cept for six belonged to the ten mtDNA haplogroups that have been detected in the Finnish population (H, I, J, K, M, T, U, V, W and X). The haplogroup frequencies of the Vitality 90+ group differed from those of the controls (P=0.01; Table 1) in that the frequency of haplogroup H was lower (P=0.001), as was also the case with the closely related haplogroup V. No difference was found in the fre- quency of subcluster H1 between the Vitality 90+ group and the controls belonging to haplogroup H. On the other

Table 1 Haplogroup frequencies among the Vitality 90+ subjects, controls and infants

Haplo- Haplogroup frequencies group Vitality 90+ Controls Infants n % n % n % H 84 37.3 204 51.0 141 54.9 I 8 3.6 10 2.5 6 2.3 J 19 8.4 25 6.3 8 3.1 K 17 7.6 24 6.0 12 4.7 M 1 0.4 4 1.0 5 1.9 T 11 4.9 22 5.5 6 2.3 U 64 28.4 82 20.5 59 23.0 V 4 1.8 16 4.0 13 5.1 W 8 3.6 5 1.3 5 1.9 X 5 2.2 7 1.8 1 0.4 Other 4 1.8 1 0.3 1 0.4 Total 225 100.0 400 100.2 257 100.0

Subjects and methods

Subjects

Samples were obtained from 225 persons aged 90 or 91 years tality 90+) living in the city of Tampere, Finland; the group prised 46 men (20.4%) and 179 women (79.6%), 161 of lived independently at home, and 63 were institutionalized. Vitality 90+ group included unrelated subjects with the of one pair of twins and one pair of siblings. The control (age range: 18–65 years; mean age: 40.5 years) consisted of healthy blood donors, samples from whom were obtained mously from the Finnish Red Cross Office in Tampere. mous samples were also obtained from 257 infants (age 2–12 months; mean: 6.5 months) born at Tampere University pital. Therefore, no information was available on the ancestry the subjects in the two control groups, although the infants born during a 10-month period suggesting that the probability

hand, the frequency of haplogroup U was higher (P=0.03) among the Vitality 90+ cases, as was the related hap- logroup K. In order to substantiate the observed differ- ences, we analysed a group of 257 infants and again found significant differences in haplogroup frequencies between Vitality 90+ and the infants (P=0.00005), but not between the controls and the infants (P=0.22).

presence or absence of various clinical phenotypes. No differences were found in the frequency of mtDNA hap- logroups among the affected and non-affected subjects, except with respect to diabetes mellitus (P=0.044), where the frequency of cluster UK was twice as high in patients as in those who were unaffected. Indeed, 15 out of the 25 patients with diabetes mellitus (60%) belonged to cluster UK, whereas only 32% of the non-diabetic subjects did so; furthermore, seven of the diabetics (28%) belonged to haplogroup K, the frequency of which was only 5% among the subjects without diabetes.

Haplogroup J was present at a higher frequency among the Vitality 90+ subjects than in either the controls or the in- fants (Table 1) supporting previous findings among Italian centenarians (De Benedictis et al. 2000). Furthermore, the frequency of subcluster J1 was 4.0% in the Vitality 90+ group and 4.5% among the controls, whereas that of sub- cluster J2 was 4.4% in Vitality 90+ and 1.8% in the con- trols, suggesting that the higher frequency of haplogroup J in Vitality 90+ is attributable to an increase in subcluster J2.

Discussion

We found significant differences in mtDNA haplogroup frequencies between the Vitality 90+ subjects and the con- trols. Haplogroup H was less frequent among the Vitality 90+ cases than among the middle-aged controls or the in- fants, whereas haplogroups J, U and K were more fre- quent. The differences in haplogroup frequencies between the three age groups were similar to the age-related trend in haplogroup frequencies detected in a series of approxi- mately 800 Italians (De Benedictis et al. 2000). Further- more, we found that the frequencies of related haplo- groups had similar tendencies to increase or decrease in most cases and, in consequence, the haplogroup cluster HV was significantly lower among the Vitality 90+ sub- jects than among the controls, whereas those of clusters UK and TJ were higher. These data suggest an association between certain mtDNA haplogroups or haplogroup clus- ters and longevity.