Centenarian Offspring Research Articles

Centenarian Offspring: A Model for Understanding Longevity

A main objective of current medical research is to improve the life quality of elderly people as priority of the continuous increase of ageing population. This phenomenon implies several medical, economic and social problems because of dramatic increase in number of non autonomous individuals affected by various pathologies. Accordingly, the research interest is focused on understanding the biological mechanisms involved in determining the positive ageing phenotype, i.e. the centenarian phenotype. In achieving this goal the choice of an appropriate study models is fundamental. Centenarians have been used as an optimal model for successful ageing. However, this model shows several limitations, i.e. the selection of appropriate controls and the use itself of the centenarians as a suitable model for healthy ageing. Thus, the interest has been centered on centenarian offspring, healthy elderly people. They may represent a model for understanding exceptional longevity for the following reasons: they exhibit a protective genetic background, cardiovascular and immunological profile, as well as a reduced rate of cognitive decline than age-matched people without centenarian relatives. Several of these aspects are summarized in this review based on the literature and the results of our studies.

Evidence for Less Marked Potential Signs of T-Cell Immunosenescence in Centenarian Offspring Than in the General Age-Matched Population

People may reach the upper limits of the human life span at least partly because they have maintained more appropriate immune function, avoiding changes to immunity termed "immunosenescence." Exceptionally long-lived people may be enriched for genes that contribute to their longevity, some of which may bear on immune function. Centenarian offspring would be expected to inherit some of these, which might be reflected in their resistance to immunosenescence, and contribute to their potential longevity. We have tested this hypothesis by comparing centenarian offspring with age-matched controls. We report differences in the numbers and proportions of both CD4(+) and CD8(+) early- and late-differentiated T cells, as well as potentially senescent CD8(+) T cells, suggesting that the adaptive T-cell arm of the immune system is more "youthful" in centenarian offspring than controls. This might reflect a superior ability to mount effective responses against newly encountered antigens and thus contribute to better protection against infection and to greater longevity.

Personality Factors in the Long Life Family Study

To evaluate personality profiles of Long Life Family Study participants relative to population norms and offspring of centenarians from the New England Centenarian Study. METHOD Personality domains of agreeableness, conscientiousness, extraversion, neuroticism, and openness were assessed with the NEO Five-Factor Inventory in 4,937 participants from the Long Life Family Study (mean age 70 years). A linear mixed model of age and gender was implemented adjusting for other covariates. A significant age trend was found in all five personality domains. On average, the offspring generation of long-lived families scored low in neuroticism, high in extraversion, and within average values for the other three domains. Older participants tended to score higher in neuroticism and lower in the other domains compared with younger participants, but the estimated scores generally remained within average population values. No significant differences were found between long-lived family members and their spouses. Personality factors and more specifically low neuroticism and high extraversion may be important for achieving extreme old age. In addition, personality scores of family members were not significantly different from those of their spouses, suggesting that environmental factors may play a significant role in addition to genetic factors.

Metabolic syndrome in the offspring of centenarians: focus on prevalence, components, and adipokines

With aging, an increased prevalence of a clustering of metabolic abnormalities has been observed. These abnormalities include obesity, dyslipidemia, hypertension, and insulin resistance and are collectively known as metabolic syndrome (MetS), a low-grade, systemic, inflammatory condition associated with an increased risk of cardiovascular disease, diabetes, and other adverse health outcomes. A number of studies have demonstrated that centenarians' offspring have a significant survival advantage and a lower risk of developing the most important age-related diseases. They therefore represent one of the best models with which to study the familiar component of human longevity. The aim of this study was to determine if the offspring of centenarians (n = 265 subjects) showed a different prevalence of MetS in comparison to the offspring of non-long-lived parents (controls, n = 101 subjects). In addition, we assessed whether centenarians' offspring showed particular features of MetS and a distinct regulation of circulating adipokines, cytokines, and metabolic mediators. Although the prevalence of MetS was quite similar both in the offspring of centenarians and the controls, MetS-affected centenarians' offspring seemed healthier, more functionally fit, and had lower resistin levels. MetS prevalence did not change in centenarians' offspring across resistin, IGF-1, and resistin/IGF-1 ratio tertiles. On the other hand, in controls, MetS prevalence strongly increased across resistin tertiles and in the third resistin/IGF-1 ratio tertile, indicating a dramatic increase in MetS prevalence when the ratio between these two factors is unbalanced, with high levels of resistin and low levels of IGF-1.

A novel B cell population revealed by a CD38/CD24 gating strategy: CD38−CD24− B cells in centenarian offspring and elderly people

The B cell arm of adaptive immunity undergoes significant modifications with age. Elderly people are characterized by impaired B cell responses reflected in a reduced ability to effectively respond against viruses and bacteria. Alterations of immunity with advancing age (immunosenescence) have been widely studied in centenarians who are considered a good example of successful aging. In recent years, attention has shifted to centenarian offspring (CO) as a model of people genetically advantaged for healthy aging and longevity. Here, we describe the preliminary characterization of a proposed new population of memory B cells, defined as CD19(+)CD38(-)CD24(-), which we find at higher frequencies in the elderly but less so in CO than healthy age-matched random controls. In addition, we found a decreased expression of RP105 (CD180), a toll-like receptor-associated molecule, on these cells. CD180 downregulation may potentially be a marker of immunosenescence. Moreover, we show that these CD19(+)CD38(-)CD24(-) B cells produce TNF and hypothesize that their observed expansion in the elderly might contribute to the increased inflammatory status sometimes designated "inflamm-aging."

Associations between longevity of parents and glucose regulation in their offspring: the KORA S4/F4 Study

Type 2 diabetes was less prevalent in studies of the offspring of centenarians and a separate study of nonagenarian siblings. We examined whether this reduction would also be found when less extreme criteria of parental longevity (a lifespan of at least 80years) were applied. Moreover, we looked for an association between parental longevity and incidence of dysglycaemia, which has not yet been reported for a population-based study group. Baseline and 7-year follow-up data on 55-74-year-old participants in the population-based German Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 cohort study were used for the analyses. Participants whose parents had died from traumatic causes were excluded. Diabetes was assessed by validated physician diagnosis or OGTTs. Using logistic regression models, adjusted OR and 95% CIs were calculated for the associations between parental longevity and the prevalence or incidence of dysglycaemia, which was defined as including either type 2 diabetes or prediabetes (defined in this study as comprising impaired glucose tolerance [IGT] and impaired fasting glucose [IFG]). In age- and sex-adjusted models, the prevalence of type 2 diabetes was lower in individuals with one (OR 0.63, 95% CI 0.43, 0.93) or two (OR 0.46, 95% CI 0.25, 0.85) long-lived parents. Among participants with normal glucose tolerance at baseline, the odds of incident dysglycaemia were lower in those with one (OR 0.65, 95% CI 0.40, 1.03) or two long-lived parents (OR 0.46, 95% CI 0.22, 0.96) after adjustment for age and sex. This study showed that longevity of the parents, defined by a lifespan of at least 80years, was associated with a lower prevalence and incidence of dysglycaemia in their offspring in an older German population.

Age-related differences in the expression of circulating microRNAs: miR-21 as a new circulating marker of inflammaging

Circulating microRNAs (miRs) have been investigated as diagnostic/prognostic biomarkers in human diseases. However, little is known about their expression throughout the aging process.Eleven healthy individuals aged 20, 80 and 100years underwent miR plasma profiling. The validation cohort consisted of 111 healthy adults (CTR) aged 20–105years and included 30 centenarians. In addition, 34 patients with cardiovascular disease (CVD) and 15 healthy centenarian offspring (CO) were enrolled.An exploratory factorial analysis grouped the miRs into three main factors: factor 1 primarily higher in 20-year-old subjects, but these differences did not reach statistical significance, factor 2 primarily higher in octogenarians and factor 3 primarily higher in centenarians. MiR-21, the most highly expressed miR of factors 2 and 3, was further validated, confirming the differences in the age groups. MiR-21 expression was higher in the CVD patients and lower in the CO compared to the age-matched CTR. MiR-21 was correlated with C-reactive protein and fibrinogen levels. TGF-β signaling was the predicted common pathway targeted by miRs of factors 2 and 3. TGF-βR2 mRNA, a validated miR-21 target, showed the highest expression in the leukocytes from a subset of the octogenarians.Our findings suggest that miR-21 may be a new biomarker of inflammation.

Impact of the genetic background on immune system

The aim of this study was to compare some immune parameters between healthy centenarian offspring (CO), healthy age‐matched old (O) and young (Y) controls to evaluate whether any difference exists in the naïve/memory compartments that might explain the familiar increased lifespan expectancy of centenarian offspring (CO). In fact it is now supposed that longevity is based on genetic background and it has been demonstrated that centenarian siblings have an increased probability to reach long life as well.MethodsPeripheral blood mononuclear cells (PBMC) were collected from CO, O and Y donors. Lymphocyte subsets were evaluated by cytofluorimetric analysis. We have studied the naïve/memory compartment in T and B cells evaluating the expression of CD45R0, CD27, CD28 (on CD4 and CD8 T cells) and IgD and CD27 (on CD19 B cells).ResultsOur results show that O show the most differentiated phenotype, Y display the less differentiated phenotype and CO show an intermediate profile between the other two control groups.ConclusionThese data support the hypothesis of a “familiar youth” of the immune system that can be a big advantage both to fight the main age‐related diseases, and to properly respond to vaccinations. So, T and B cell subset changes could represent an hallmark of successful or unsuccessful ageing and could be used as a biomarker of human life span.This work was supported by the Italian Ministry of Education, University and Research grant (Does parental longevity impact on the health ageing of their offspring? An immunological and genetic study) to C. Caruso.

B Cells Compartment in Centenarian Offspring and Old People

Immunosenescence is considered a major contributory factor to the increased frequency of morbidity and mortality among elderly. On the other hand centenarians are considered the best example of successful ageing. To gain insight into mechanisms of immunosenescence and its clinical relevance, a possible model is represented by centenarians and/or their offspring. Nowadays centenarians are not more a curiosity, but in Europe are 1/8000 inhabitants and it has been demonstrated that the centenarian offspring, who are typically in their 70s and 80s, have a survival advantage when compared with age-matched controls whose parents died at an average life expectancy. Then again, studies on immunosenescence focus mainly on T cell impairment, although B cells are also affected. So, in the present preliminary report, we have studied B cell compartment in two classes of individuals, old people and centenarian offspring. B cell compartment was analysed using IgD and CD27 antibodies which characterize naïve B cells (IgD(+) CD27(-)), memory unswitched B cells (IgD(+)CD27(+)), memory switched B cells(IgD(-)CD27(+)) and double negative B cells (DN) (IgD(-)CD27(-)), i.e. exhausted memory cells. As expected, in both cohorts we observed a decreased B cell count. However, in centenarian offspring, naïve B cells are more abundant whereas exhausted memory cells (DN B cells, IgD(-)CD27(-)) do not show the increase that we have previously demonstrated in healthy elderly donors. These data are similar to that found in previously experiments on young subjects. So, our preliminary results show that centenarian offspring do not have the typical trend of memory/naive B cell subsets observed in elderly people and this is in agreement with the higher levels of IgM in the serum of centenarian offspring in comparison with data obtained in age-matched controls. This reservoir of naive B cell might be one of the causes that make centenarian offspring able to keep fighting off new infections, hence prolonging their life. So, B cell subset changes could represent a hallmark of successful or unsuccessful ageing and could be used as a biomarker of human life span, potentially useful for the evaluation of anti-ageing treatment.

Personality Traits of Centenarians' Offspring

To determine whether the offspring of centenarians have personality characteristics that are distinct from the general population. Case-control. Nationwide U.S. sample. Unrelated offspring of centenarians (n=246, mean age 75) were compared with published norms. Using the NEO-Five-Factor Inventory (NEO-FFI) questionnaire, measures of the personality traits neuroticism, extraversion, openness, agreeableness, and conscientiousness were obtained. T-scores and percentiles were calculated according to sex and used to interpret the results. Male and female offspring of centenarians scored in the low range of published norms for neuroticism and in the high range for extraversion. The women also scored comparatively high in agreeableness. Otherwise, both sexes scored within normal range for conscientiousness and openness, and the men scored within normal range for agreeableness. Specific personality traits may be important to the relative successful aging demonstrated by the offspring of centenarians. Similarities across four of the five domains between male and female offspring is noteworthy and may relate to their successful aging. Measures of personality are an important phenotype to include in studies that assess genetic and environmental influences of longevity and successful aging.

B cells compartement in centenarian offspring and old people

Immunosenescence is considered a major contributory factor to the increased frequency of morbidity and mortality among elderly. Immunosenescence studies focus mainly on T cells, although B cells are affected too. In our studies we analyzed B cells in two classes of individuals: old people (O), (age range 70‐85 years) and centenarian offspring (CA). Our data showed difference in number of B cells from O and CA. B cells were analyzed according to the expression of sIgD and CD27. B cells were classified as follows: IgD+CD27−(naïve),IgD+CD27+(unswitched‐memory),IgD−CD27+ (switched ‐memory) and IgD−CD27−(double negative, DN). As expected, in both cohorts we observed a marked decreased of B cell count although within the B cell population, CA do not behave as O subjects. Indeed, in CA , naïve B cells are more abundant whereas DN B cells don't show the typical increase that we have previously demonstrated in healthy elderly donors. So, B cells of the CA seem to be more similar to that of young respect to the old one. B cell subsets changes could represent a hallmark of immunosenescence and could be used as a biomarker of human life span, potentially useful for the evaluation of anti‐ageing treatment.This work was supported by grants from the Italian Ministry of Education, University and Research (MIUR, ex 40%)

Centenarian Offspring: Start Healthier and Stay Healthier

To assess the relative incidence of age-related diseases in a group of centenarian offspring who have thus far been considered to be predisposed to "healthy" aging. Longitudinal study. Nationwide sample. Four hundred forty centenarian offspring and 192 referent cohort subjects who met inclusion criteria of having initial and follow-up health questionnaire data available. Median age of both cohorts was 72 at the initial health questionnaire. Initial health questionnaires were collected from 1997 to 2006. Follow-up questionnaires were collected from 2004 to 2007. The mean period of follow-up was 3.5+/-1.7 years for the centenarian offspring and 3.9+/-2.2 years for the referent cohort. During the follow-up period, centenarian offspring had a 78% lower risk of myocardial infarction (P<.04), 83% lower risk of stroke (P<.004), and 86% lower risk of developing diabetes mellitus (P<.005) than the referent cohort. There were no significant differences in new onset of other age-related diseases. Additionally, centenarian offspring were 81% less likely to die (P<.01) than the referent cohort during the follow-up. These findings suggest that centenarian offspring retain some important cardiovascular advantages over time over similarly aged referent cohort subjects. These findings reinforce the notion that there may be physiological reasons that longevity runs in families and that centenarian offspring are more likely to age in better cardiovascular health and with a lower mortality than their peers.

Abstract ED04-02: The role of genes in protecting against age-related disease in cancer

Abstract ED04-02 Despite evidence for a substantial genetic component, the inherited biological factors that promote extended life span (longevity) in humans remain unknown. We have comprehensively characterized over 450 Ashkenazi Jewish families with exceptional longevity (survival in good health to at least age 95) and have identified several biological markers that may be causative in their longevity. These subjects and their offspring have 2-3 fold increases in rates of polymorphism in 3 genes all validated by other in other studies. Two genes are regulating lipoprotein--cholesterol ester transfer protein (CETP) and apolipoprotein C-3 (APOC-3)--and decrease in plasma levels CETP and APOC-3. Another gene is Adiponectin (ADIPOQ) regulating insulin action and inflammation. We have also demonstrated that these genotypes and phenotypes are associated with less hypertension (HTN), cardiovascular disease (CVD) and metabolic syndrome (MS), and improved cognitive function. However, these genes have not been shown yet to protect against cancer. Modulation of GH/IGF-1 axis is conferring longevity in mamalians and low IGF-1 levels is associated with decreased rates of cancers in humans. We demonstrated a gender-specific increase in serum IGFI associated with a smaller stature in female offspring of centenarians. Sequence analysis of the IGF1 and IGF1 receptor (IGF1R) genes of female centenarians showed overrepresentation of heterozygous mutations in the IGF1R gene among centenarians relative to controls that are associated with high serum IGFI levels and reduced activity of the IGFIR as measured in transformed lymphocytes. Thus, genetic alterations in the human IGF1R that result in altered IGF signaling pathway confer an increase in susceptibility to human longevity, suggesting a role of this pathway in modulation of human lifespan, possibly by protecting against cancer. Citation Information: Cancer Prev Res 2008;1(7 Suppl):ED04-02.

Functionally significant insulin-like growth factor I receptor mutations in centenarians.

Rather than being a passive, haphazard process of wear and tear, lifespan can be modulated actively by components of the insulin/insulin-like growth factor I (IGFI) pathway in laboratory animals. Complete or partial loss-of-function mutations in genes encoding components of the insulin/IGFI pathway result in extension of life span in yeasts, worms, flies, and mice. This remarkable conservation throughout evolution suggests that altered signaling in this pathway may also influence human lifespan. On the other hand, evolutionary tradeoffs predict that the laboratory findings may not be relevant to human populations, because of the high fitness cost during early life. Here, we studied the biochemical, phenotypic, and genetic variations in a cohort of Ashkenazi Jewish centenarians, their offspring, and offspring-matched controls and demonstrated a gender-specific increase in serum IGFI associated with a smaller stature in female offspring of centenarians. Sequence analysis of the IGF1 and IGF1 receptor (IGF1R) genes of female centenarians showed overrepresentation of heterozygous mutations in the IGF1R gene among centenarians relative to controls that are associated with high serum IGFI levels and reduced activity of the IGFIR as measured in transformed lymphocytes. Thus, genetic alterations in the human IGF1R that result in altered IGF signaling pathway confer an increase in susceptibility to human longevity, suggesting a role of this pathway in modulation of human lifespan.

Cardiovascular risk factors in centenarians

Several studies have shown that centenarians have better cardiovascular risk profiles compared to younger old people. Some reports have revealed that cardiovascular diseases (i.e. hypertension, diabetes, angina and/or myocardial infarction) are less common in centenarians respect to 70 and 80 years old persons. In order to explain this evidence, there is a growing number of hypothesis that consider a combination of genetic factors and lifestyle aspects to elucidate the exceptional longevity of centenarians, able to overcome the most frequent mortality cause, which is a cardiovascular event. It has been suggested that a role on this better cardiovascular risk profile may be played by the increasing use of pharmacologic treatments in the elderly population (specially for hypertension and dyslipidemia), but the contribution of drug treatments to promote extreme longevity is not confirmed. Furthermore, centenarians in general have needed fewer drugs at younger ages due to a healthy lifestyle. The importance of the genetic contribution is demonstrated by the inheritance of low-risk cardiovascular profiles in centenarian offspring and lower prevalence of cardiovascular diseases in this population as compared with their spouses or with age-matched subjects without centenarian parents. Another advantage in centenarians’ offspring seems to be a delay in the onset for cardiovascular diseases, respect to age- and sex-matched controls. Cardiovascular risk factors mirror the factors that contribute to longevity. Hence, it is not surprising that these risk factors are less prevalent in centenarians when compared to younger old individuals.

Inflammatory networks in ageing, age-related diseases and longevity

Inflammation is considered a response set by the tissues in response to injury elicited by trauma or infection. It is a complex network of molecular and cellular interactions that facilitates a return to physiological homeostasis and tissue repair. The individual response against infection and trauma is also determined by gene variability. Ageing is accompanied by chronic low-grade inflammation state clearly showed by 2–4-fold increase in serum levels of inflammatory mediators. A wide range of factors has been claimed to contribute to this state; however, the most important role seems to be played by the chronic antigenic stress, which affects immune system thorough out life with a progressive activation of macrophages and related cells. This pro-inflammatory status, interacting with the genetic background, potentially triggers the onset of age-related inflammatory diseases as atherosclerosis. Thus, the analysis of polymorphisms of the genes that are key nodes of the natural immunity response might clarify the patho-physiology of age-related inflammatory diseases as atherosclerosis. On the other hand, centenarians are characterized by marked delay or escape from age-associated diseases that, on average, cause mortality at earlier ages. In addition, centenarian offspring have increased likelihood of surviving to 100 years and show a reduced prevalence of age-associated diseases, as cardiovascular disease (CVD) and less prevalence of cardiovascular risk factors. So, genes involved in CVD may play an opposite role in human longevity. Thus, the model of centenarians can be used to understand the role of these genes in successful and unsuccessful ageing. Accordingly, we report the results of several studies in which the frequencies of pro-inflammatory alleles were significantly higher in patients affected by infarction and lower in centenarians whereas age-related controls displayed intermediate values. These findings point to a strong relationship between the genetics of inflammation, successful ageing and the control of cardiovascular disease at least in men, in which these studies were performed. These data are also briefly discussed in the light of antagonistic pleiotropy theory and in order to pursuit a pharmacogenomics approach.

Serum heat shock protein 70 level as a biomarker of exceptional longevity

Heat shock proteins are highly conserved proteins that, when produced intracellularly, protect stress exposed cells. In contrast, extracellular heat shock protein 70 (Hsp70) has been shown to have both protective and deleterious effects. In this study, we assessed heat shock protein 70 for its potential role in human longevity. Because of the importance of HSP to disease processes, cellular protection, and inflammation, we hypothesized that: (1) Hsp70 levels in centenarians and centenarian offspring are different from controls and (2) alleles in genes associated with Hsp70 explain these differences. In this cross-sectional study, we assessed serum Hsp70 levels from participants enrolled in either the New England Centenarian Study (NECS) or the Longevity Genes Project (LGP): 87 centenarians (from LGP), 93 centenarian offspring (from NECS), and 126 controls (43 from NECS, 83 from LGP). We also examined genotypic and allelic frequencies of polymorphisms in HSP70-A1A and HSP70-A1B in 347 centenarians (266 from the NECS, 81 from the LGP), 260 NECS centenarian offspring, and 238 controls (NECS: 53 spousal controls and 106 septuagenarian offspring controls; LGP: 79 spousal controls). The adjusted mean serum Hsp70 levels (ng/mL) for the NECS centenarian offspring, LGP centenarians, LGP spousal controls, and NECS controls were 1.05, 1.13, 3.07, 6.93, respectively, suggesting that a low serum Hsp70 level is associated with longevity; however, no genetic associations were found with two SNPs within two hsp70 genes.

Lower All‐Cause, Cardiovascular, and Cancer Mortality in Centenarians' Offspring

To assess the cause of death for centenarians' offspring and controls. Cross-sectional study. Community-based, nationwide sample. Family pedigree information was collected on 295 offspring of centenarians (from 106 families with a parent already enrolled in the nationwide New England Centenarian Study) and on 276 controls (from 82 control families) from 1997 to 2000. Controls were individuals whose parents were born in the same year as the centenarians but at least one of whom died at the average life expectancy. Age at death and cause of death. Centenarians' offspring had a 62% lower risk of all-cause mortality (P<.001), a 71% lower risk of cancer-specific mortality (P=.002), and an 85% lower risk of coronary heart disease-specific mortality (P<.001). Significant differences were not found for other causes of death. However of those who died centenarian offsprings dead at a significantly younger age than controls. These findings suggest that centenarians' offspring have lower all-cause mortality rates and cause-specific mortality rates for cancer and coronary heart disease. These results suggest that mechanisms for survival to exceptional old age may go beyond the avoidance or delay of cardiovascular disease and also include the avoidance or delay of cancer. Moreover survival advantage of centenarian offsprings may not be due to factors related to childhood mortality. Ultimately, survival to exceptional old age may involve lower susceptibility to a broad range of age-related diseases, perhaps secondary to inhibition of basic mechanisms of aging.

Cardiovascular disease delay in centenarian offspring: role of heat shock proteins.

Cardiovascular disease is a major cause of morbidity and mortality of older Americans. We have demonstrated recently that centenarian offspring, when compared with age-matched controls, avoid and/or delay cardiovascular disease and cardiovascular risk factors. Given recent evidence suggesting that higher circulating levels of HSP70 predict the future development of cardiovascular disease in established hypertensives and a recent study demonstrating a decrease in HSP60 and HSP70 with advancing age, we hypothesized that HSP70 levels would be lower in centenarian offspring compared with controls. The circulating serum concentration of HSP70 in 20 centenarian offspring and 9 spousal controls was analyzed using a modified HSP70 ELISA method. Centenarian offspring showed approximately 10-fold lower levels of circulating serum HSP70 compared with spousal controls (P <.001). The exact biological significance of the extremely low levels of circulating serum HSP70 observed in centenarian offspring thus far is not clear. However, circulating HSP has been shown to correlate in diseases or disorders in which there is destruction or damage to target tissues or organs, including cardiovascular diseases and numerous autoimmune disorders. We hypothesize that low levels of circulating serum HSP70 may be an indicator of a healthy state and point to longevity of the host; therefore, our results suggest that levels of circulating serum HSP70 may be a marker for longevity.

Cardiovascular disease delay in centenarian offspring.

Previously, the authors have shown that an important component of the ability to survive to exceptionally old age is family health history. This study assessed the age at onset of age-related diseases in centenarian offspring. The health histories of 177 offspring of centenarians enrolled in the nationwide New England Centenarian Study, and 166 controls were assessed from 1997 to 2000. Controls were the offspring of parents born in the same years as the centenarians but at least one of whom died at average life expectancy. Ages at onset of heart disease, hypertension, diabetes, cancer, osteoporosis, cataracts, glaucoma, macular degeneration, depression, thyroid disease, and stroke were compared in the two groups. The median ages of onset for coronary heart disease (p <.001), hypertension (p <.001), diabetes (p =.002), and stroke (p =.017) were significantly delayed in the centenarian offspring by 5.0, 2.0, 8.5, and 8.5 years, respectively, compared with the age-matched controls. Adjusted hazard ratios were 0.388 (p =.0004), 0.39 (p <.0001), 0.302 (p =.008), and 0.328 (p =.06). No differences were found in the ages of onset for the other diseases investigated. The offspring of centenarians show a marked delay in the age of onset for cardiovascular disease, diabetes, hypertension, and stroke but not for other age-related diseases such as cancer, osteoporosis, and thyroid disease. These results suggest that the children of centenarians may be following in their parents' footsteps, markedly delaying the onset of lethal diseases that commonly affect older persons.