Gerard J. Ligthart

Necessity of the assessment of health status in human immunogerontological studies: Evaluation of the senieur protocol

Disease is frequent in ageing, and the many conflicting results in studies of the ageing process can be due to the presence of factors such as underlying disease or the use of medication. For immunogerontology, a solution to this problem was initiated in 1984 by a working party of EURAGE, the European Communitys Concerted Action Programme on Ageing and Diseases. A protocol defining strict admission criteria to studies of ageing, the SENIEUR protocol, was elaborated. This protocol intends to limit the influence of disease and/or medication and to standardize admission criteria to immunogerontological studies. In subjects fulfilling the SENIEUR criteria, we found less immunological defects with ageing than generally stated. This could mean that many studies performed in not-optimally healthy subjects describe defects that are not a consequence of the ageing process, but could be a result of underlying disease or of the influence of medication. For lymphocyte subsets, certain changes are only found in the comparison of SENIEUR groups of young and aged, while other changes are only found when non-healthy groups are compared. The occurrence of monoclonal gammopathies and autoantibodies was increased in ageing, but was also influenced by health status. Experience of other groups, and the objections against the protocol are discussed.

Health care for older persons, a country profile : The Netherlands

HEALTH CARE SYSTEM In the Netherlands, there are four medical specialties clinical geriatrics, nursing home medicine, social geriatrics, and geriatric psychiatry that focus primarily on geriatric care. Nevertheless, and despite a high rate of institutionalization (8% of older people are in residential or nursing homes), the general practitioner continues to act as the gatekeeper for additional intensive medical care services in most geriatric situations. The objective of this paper is to describe how medical care for older people functions in the Netherlands.

Annually repeated influenza vaccination improves humoral responses to several influenza virus strains in healthy elderly

The benefit of annually repeated influenza vaccination on antibody formation is still under debate. In this study the effect of annually repeated influenza vaccination on haemagglutination inhibiting (HI) antibody formation in the elderly is investigated. Between 1990 and 1993 healthy young and elderly, both selected by the SENIEUR protocol, were vaccinated consecutively with commercially available influenza vaccines. The elderly had a lower HI antibody response after one vaccination as compared to the young against the A/Taiwan/1/86 (HINI), B/Yamagata/16/88 and B/Panama/45/90 strains. Annually repeated vaccination did not result in a decrease of the HI antibody titres against the A and B vaccine strains in both age groups. Moreover, the elderly had a significantly higher HI titre against the B strains after the second vaccination as compared to the first, resulting in comparable HI titres for young and elderly. Thus, annually repeated vaccination has a beneficial effect on the antibody titre against influenza virus and can contribute to a better antibody-response in the elderly.

Improvement of the immunoglobulin subclass response to influenza vaccine in elderly nursing-home residents by the use of high-dose vaccines

To investigate the effects of age and antigen dose (10, 20, 60 micrograms) on the immunoglobulin (sub) class distribution following influenza vaccination, antibody responses in 79 elderly nursing home residents were compared with the responses in 100 young subjects. At a 10 micrograms dose the IgM, IgG3 and IgA1 responses were comparable in both age groups, whereas the IgG, IgG1 and haemagglutination inhibition (HI) responses were twofold lower in the elderly. A 20 micrograms dose increased the IgG, IgG1 and HI levels in the elderly to the levels in the young and the IgA1 to significantly higher levels. A 60 micrograms dose increased antibody levels in the young, but did not further increase the response in the elderly. The 20 micrograms dose might represent a higher level of protection in the elderly.

Longevity and Heredity in Humans

Several arguments support the idea of a link between longevity and heredity, both in experimental animals and in the human species. In mice, genes in the major histocompatibility complex (MHC) are associated with a significant effect on life span. Results of analogous studies in man are confusing and contradictory. We have therefore investigated the question of an association of the human leucocyte antigen (HLA) and longevity in a large and ethnically homogeneous population. Our study population consisted of all 964 available inhabitants aged 85 years and over in the Dutch community of Leiden (pop. 104,000). Our control group comprised 2444 young inhabitants, aged 20-35 years, with an identical ethnic and demographic background. In addition, control groups of different age-brackets from the same region were used. Two antigens differed in frequency: HLA-B40 was lower and HLA-DR5 was higher in the group of 85 years and over, as compared to the control group, aged 20-35 years. Both differences were more evident in females. No major disease associations with HLA-B40 or HLA-DR5 have been reported. It is unlikely that these results are a chance observation: the overall similarity of the HLA pattern of the old and young age groups is a confirmation of their identical ethnic and demographic background and the changes as observed in the different age-groups were gradual. The biological meaning of these results is still unclear.

Altered antibody response to influenza H1N1 vaccine in healthy elderly people as determined by HI, ELISA, and neutralization assay.

To determine the influence of ageing per se as well as of priming histories on the antibody response to influenza vaccination, haemagglutination inhibition (HI), ELISA IgG, IgA, IgM and neutralizing antibody titres were studied in 43 healthy young subjects (mean age 23 years) and 55 healthy elderly people (mean age 79 years). The HI and ELISA IgG responses to the A/Guizhou/54/89 strain (H3N2) for which both the young and the elderly had similar priming histories were equal. By contrast, the HI and IgG responses to A/Taiwan/1/86 (H1N1), where the priming histories were different, were lower in the elderly (P < 0.05). Influenza‐specific IgA responses in the elderly tended to be higher for all vaccine strains. Influenza‐specific postvaccination IgM titres were similar or tended to be higher in the elderly. A subgroup of elderly subjects (18%) who did not express HI activity to the A/Taiwan/1/86 (H1N1) vaccine strain, reacted in the HI assay with the closely related A/Singapore/6/86 (H1N1) strain. These elderly people, however, produced IgG antibodies which neutralized A/Taiwan/1/86 virus in vitro. It is concluded that the elderly are capable of mounting antibody responses similar to those observed in the young. Moreover, the observed age‐related differences in antibody responses to H1N1 strains are probably not due to ageing of the immune system itself, but are determined by differences in priming histories. J. Med. Virol. 55:82–87, 1998.

Nocturnal Activity and Immobility across Aging (50–98 Years) in Healthy Persons

Objective: To measure the influence of age on measures of nocturnal activity and immobility in 100 healthy subjects aged 50 to 98 years.

The Association Between Human Leucocyte Antigens (HLA) and Mortality in Community Residents Aged 85 and Older

OBJECTIVE: The association between Human Leucocyte Antigens (HLA) and aging was investigated. It is possible that HLA antigens are associated with longevity, either indirectly through disease associations or directly through involvement in the aging mechanism.

Correlation between the antibody response to influenza vaccine and helper T cell subsets in healthy ageing

To investigate the effects of the altered composition of the helper T cell compartment in ageing on the humoral response to influenza vaccine, we investigated correlations between helper T cell subsets and anti-influenza antibody responses in 23 JUNIEUR healthy young and 41 SENIEUR healthy elderly subjects. Naive helper T cell numbers (CD4+ CD45RA+) were negatively correlated with antibody production to two of the four strains investigated in JUNIEURS only. By contrast, memory helper T cell numbers (CD4+CD45ROhi) were positively correlated with in vivo IgG antibody titres to three of the four vaccine strains. Age-related differences in the composition of the helper T cell compartment, however, did not explain the lower IgG antibody response that was observed to two of the four vaccine strains examined.