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Although chronic infection with cytomegalovirus ( CMV) is known to drive T lymphocytes toward a senescent phenotype, it remains controversial whether and how CMV can cause coronary heart disease ( CHD). To explore whether CMV seropositivity or T-cell populations associated with immunosenescence were informative for adverse cardiovascular outcome in the very old, we prospectively analyzed peripheral blood samples from 751 octogenarians (38% males) from the Newcastle 85+ study for their power to predict survival during a 65-month follow-up (47.3% survival rate). CMV-seropositive participants showed a higher prevalence of CHD (37.7% vs. 26.7%, P = 0.030) compared to CMV-seronegative participants together with lower CD4/ CD8 ratio (1.7 vs. 4.1, P < 0.0001) and higher frequencies of senescence-like CD4 memory cells (41.1% vs. 4.5%, P < 0.001) and senescence-like CD8 memory cells ( TEMRA, 28.1% vs. 6.7%, P < 0.001). CMV seropositivity was also associated with increased six-year cardiovascular mortality ( HR 1.75 [1.09-2.82], P = 0.021) or death from myocardial infarction and stroke ( HR 1.89 [107-3.36], P = 0.029). Gender-adjusted multivariate Cox regression analysis revealed that low percentages of senescence-like CD4 T cells ( HR 0.48 [0.32-0.72], P < 0.001) and near-senescent ( CD27 negative) CD8 T cells ( HR 0.60 [0.41-0.88], P = 0.029) reduced the risk of cardiovascular death. For senescence-like CD4, but not near-senescent CD8 T cells, these associations remained robust after additional adjustment for CMV status, comorbidities, and inflammation markers. We conclude that CMV seropositivity is linked to a higher incidence of CHD in octogenarians and that senescence in both the CD4 and CD8 T-cell compartments is a predictor of overall cardiovascular mortality as well as death from myocardial infarction and stroke. [ABSTRACT FROM AUTHOR]

Author(s): Tom B L Kirkwood [1] Merchants of Immortality: Chasing the Dream of Human Life Extension Stephen S Hall Houghton Mifflin Company, 2003 439 pp. , $25.00 For a work [...]

Author(s): Rudi G.J. Westendorp [1, 3]; Frederique M. van Dunne [1]; Tom B.L. Kirkwood [2]; Frans M. Helmerhorst [1]; Tom W.J. Huizinga [1] To the editor Whenever a gene for [...]

To re-examine the correlation between mt DNA variability and longevity, we examined mt DNAs from samples obtained from over 2200 ultranonagenarians (and an equal number of controls) collected within the framework of the GEHA EU project. The samples were categorized by high-resolution classification, while about 1300 mt DNA molecules (650 ultranonagenarians and an equal number of controls) were completely sequenced. Sequences, unlike standard haplogroup analysis, made possible to evaluate for the first time the cumulative effects of specific, concomitant mt DNA mutations, including those that per se have a low, or very low, impact. In particular, the analysis of the mutations occurring in different OXPHOS complex showed a complex scenario with a different mutation burden in 90+ subjects with respect to controls. These findings suggested that mutations in subunits of the OXPHOS complex I had a beneficial effect on longevity, while the simultaneous presence of mutations in complex I and III (which also occurs in J subhaplogroups involved in LHON) and in complex I and V seemed to be detrimental, likely explaining previous contradictory results. On the whole, our study, which goes beyond haplogroup analysis, suggests that mitochondrial DNA variation does affect human longevity, but its effect is heavily influenced by the interaction between mutations concomitantly occurring on different mt DNA genes. [ABSTRACT FROM AUTHOR]

Clear evidence exists for heritability of human longevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the largest genome-wide linkage scan thus far reported. Linkage analyses included 2118 nonagenarian Caucasian sibling pairs that have been enrolled in 15 study centers of 11 European countries as part of the Genetics of Healthy Aging ( GEHA) project. In the joint linkage analyses, we observed four regions that show linkage with longevity; chromosome 14q11.2 ( LOD = 3.47), chromosome 17q12-q22 ( LOD = 2.95), chromosome 19p13.3-p13.11 ( LOD = 3.76), and chromosome 19q13.11-q13.32 ( LOD = 3.57). To fine map these regions linked to longevity, we performed association analysis using GWAS data in a subgroup of 1228 unrelated nonagenarian and 1907 geographically matched controls. Using a fixed-effect meta-analysis approach, at the TOMM40/ APOE/ APOC1 gene locus showed significant association with longevity ( P-value = 9.6 × 10−8). By combined modeling of linkage and association, we showed that association of longevity with APOEε4 and APOEε2 alleles explain the linkage at 19q13.11-q13.32 with P-value = 0.02 and P-value = 1.0 × 10−5, respectively. In the largest linkage scan thus far performed for human familial longevity, we confirm that the APOE locus is a longevity gene and that additional longevity loci may be identified at 14q11.2, 17q12-q22, and 19p13.3-p13.11. As the latter linkage results are not explained by common variants, we suggest that rare variants play an important role in human familial longevity. [ABSTRACT FROM AUTHOR]

Discusses a study which tested the hypothesis that cardiovascular mortality in old age is the late consequence of an evolutionary programming for proinflammatory responses. Physiological implications of tumor necrosis factor-α and interleukin-10; Genetic aspects of cardiovascular death; Overview of the antagonistic pleiotropy theory.

The article presents an obituary for British geneticist Robin Holliday.

The article presents information on the science of ageing. For more than 70,000 days of the last two centuries, life expectancy within Great Britain increased by an amount of 5 hours, adding up to a total of 40 years, a doubling in the average life-span over just eight generations. Improvements in sanitation, nutrition, housing and education all worked together to reduce the heavy burden of infectious disease that struck down the predecessors at startling rates, particularly at young ages. This continued with the introduction of vaccines and antibiotics. In spite of a widely held belief that some kind of biological clock programmes the ageing process, it is necessary to know that this is highly unlikely. For most natural populations, mortality due to accidents, predation, starvation, disease and cold is such that death occurs well before old age. This means that whatever functional value is assigned to a clock for ageing, for example as a means to control population growth, there is scant evidence that such value is actually realised. Factors that increase exposure to damage accelerate ageing. Factors that boost repair functions slow it down.

The author asserts that addressing the case of missing data on health conditions for the 85-plus segment of Great Britain's population will help in giving them effective health care. The Newcastle 85+ Cohort Study assessed the health spectrum of the oldest old, identified factors contributing to health maintenance and independence and advocated understanding of aging's biological nature. The study showed prevalent chronic diseases and few limitations in daily activities of the oldest old.

A conference paper on the modeling of lipid metabolism to improve healthy aging is presented. It discusses the important role of lipid metabolism in human longevity and healthy aging. It also discusses a mathematical modeling to infer nutrition-based interventions, which may help to prevent the dysregulation of lipid metabolism that leads to cardiovascular disease.

This study examined respiratory muscle strength using the POWERbreathe® inspiratory muscle trainer (i.e., ‘S-Index’) before and after repeated-sprint cycling for comparison with maximal inspiratory pressure (MIP) values obtained during a Mueller maneuver. The S-Index was measured during six trials across two sessions using the POWERbreathe® and MIP was measured during three trials in a single session using a custom-made manometer in seven recreationally active adults. Global respiratory muscle strength was measured using both devices before and after the performance of sixteen, 6-s sprints on a cycle ergometer. Intraclass correlation coefficients for the POWERbreathe® S-index indicated excellent (p < 0.05) trial-to-trial (r = 0.87) and day-to-day (r = 0.90) reliability yet there was no significant correlation (r = -0.35, p = 0.43) between the S-Index measured using the POWERbreathe® and MIP measured during a Mueller maneuver. Repeated-sprint cycling had no effect on respiratory muscle strength as measured by the POWERbreathe® (p > 0.99) and during the Mueller maneuver (p > 0.99). The POWERbreathe® S-Index is a moderately reliable, but not equivalent, measure of MIP determined during a Mueller maneuver. Furthermore, repeated-sprint cycling does not induce globalized respiratory muscle fatigue in recreationally-active adults. [ABSTRACT FROM AUTHOR]