Developmental aspects of a life course approach to healthy ageing.

We examine the mechanistic basis and wider implications of adopting a developmental perspective on human ageing. Previous models of ageing have concentrated on its genetic basis, or the detrimental effects of accumulated damage, but also have raised issues about whether ageing can be viewed as adaptive itself, or is a consequence of other adaptive processes, for example if maintenance and repair processes in the period up to reproduction are traded off against later decline in function. A life course model places ageing in the context of the attainment of peak capacity for a body system, starting in early development when plasticity permits changes in structure and function induced by a range of environmental stimuli, followed by a period of decline, the rate of which depends on the peak attained as well as the later life conditions. Such path dependency in the rate of ageing may offer new insights into its modification. Focusing on musculoskeletal and cardiovascular function, we discuss this model and the possible underlying mechanisms, including endothelial function, oxidative stress, stem cells and nutritional factors such as vitamin D status. Epigenetic changes induced during developmental plasticity, and immune function may provide a common mechanistic process underlying a life course model of ageing. The life course trajectory differs in high and low resource settings. New insights into the developmental components of the life course model of ageing may lead to the design of biomarkers of later chronic disease risk and to new interventions to promote healthy ageing, with important implications for public health.

Healthy Aging Biomarkers: The INSPIRE's Contribution.

The find solutions for optimizing healthy aging and increase health span is one of the main challenges for our society. A novel healthcare model based on integration and a shift on research and care towards the maintenance of optimal functional levels are now seen as priorities by the WHO. To address this issue, an integrative global strategy mixing longitudinal and experimental cohorts with an innovative transverse understanding of physiological functioning is missing. While the current approach to the biology of aging is mainly focused on parenchymal cells, we propose that age-related loss of function is largely determined by three elements which constitute the general ground supporting the different specific parenchyma: i.e. the stroma, the immune system and metabolism. Such strategy that is implemented in INSPIRE projects can strongly help to find a composite biomarker capable of predicting changes in capacity across the life course with thresholds signalling frailty and care dependence.

COVID-19 and Intrinsic Capacity.

The SARS-CoV-2 infection is particularly associated with negative outcomes (i.e., serious disease, death) in frail older people, independently of where they live. Furthermore, the period of pandemic (with its lockdowns, social distancing, fragmentation of care…) has significantly changed the environment in which older people live. It is likely that, when the pandemic will be over, an acceleration of the aging process will be observed for many persons, independently of whether they have been infected or not by the SARS-CoV-2. The World report on ageing and health, published by the World Health Organization, proposes the concept of intrinsic capacity (i.e., the composite of all the physical and mental capacities of the individual) as central for healthy ageing. The routine assessment of biological age through constructs such as intrinsic capacity might have allowed a better understanding of the functional trajectories and vulnerabilities of the individual, even during a catastrophic event as the one we are currently living. In the present article, we describe how COVID-19 has affected the persons' intrinsic capacity, and how the wide adoption of the intrinsic capacity model may support the modernization of our systems and bring them closer to the individual.

Ross River virus infection on the North Coast of New South Wales.

A retrospective follow-up survey was undertaken of residents of the North Coast of New South Wales infected with Ross River virus in 1992. The aims of the study were to describe the epidemiology and acute symptomatology of Ross River virus infection, its natural history during the first 12 months of infection, and its effects on those infected. Questionnaires were distributed to both cases and their medical practitioners. Of 129 people infected, aged between six and 85 years, 81 (63 per cent) were male and 48 (37 per cent) were female. The peak age-specific incidence was in the age group 50 to 59 years. The most common symptoms were arthralgia (95 per cent) and tiredness (91 per cent). Over 60 per cent took time off work. At 12 months follow-up, over 50 per cent reported persistent arthralgia, 35 per cent reported persistent tiredness and 15 per cent were still unable to carry out their normal activities. The median duration of symptoms was in the range 7 to 12 months, and of incapacity was in the range five weeks to three months. There were some differences from previous reports of Ross River virus outbreaks, in the incidence of major symptoms and the duration of illness and incapacity. These are likely to be at least partly due to inconsistent measurement methods. In this study, there were systematic differences between medical practitioners' and patients' estimates of periods of incapacity. Previous estimates of the direct economic costs and indirect human costs of infection based on data obtained from medical practitioners, although alarming, are almost certainly underestimates.

Hepatitis C virus infection: impacts on behaviour and lifestyle.

A cross-sectional study was conducted of persons notified with hepatitis C virus (HCV) infection on the NSW North Coast during 1993 and 1994. The personal impact of infection was investigated using a self-administered questionnaire. Many cases were currently well, however nearly half reported fatigue and other adverse physical/mental/social outcomes were noted. Tobacco use by subjects was high. People with HCV infection require continued support via appropriate screening, referral and treatment services; access to information; and countering community discrimination, stereotyping and concern about HCV.

The vaccination status of aboriginal children in the North Coast Health Region of New South Wales.

OBJECTIVE: To determine the vaccination status of Aboriginal children resident in the North Coast Health Region of NSW. DESIGN: Cross-sectional descriptive study. SETTING AND PARTICIPANTS: The vaccination status of Aboriginal children aged 4 months to 11 years and resident in selected villages/isolated communities, small and large towns in the North Coast Health Region of NSW was determined by review of vaccination records. Data were obtained from general practitioners, the Aboriginal Health Service, Community Health Centres and Local Government Councils. MAIN OUTCOME MEASURES: Vaccination status according to the childhood immunisation schedule recommended by the National Health and Medical Research Council, defined as fully or partially documented, with a generous lag time. RESULTS: The study population comprised 1179 children--55% of the estimated Aboriginal population under 12 years of age in the North Coast Health Region. Data collection on Sabin vaccine was incomplete and was not included in the analysis. Of 1094 children whose records were analysed, 9% had fully documented and 27% fully or partially documented evidence of up-to-date vaccinations. For measles vaccination, 28% of children aged 18 months or more had fully documented and 35% fully or partially documented evidence of vaccination. There was no fully documented evidence of any vaccinations for 52% of children. CONCLUSION: The vaccination status of Aboriginal children in the North Coast Health Region is poor. The 1989-1990 National Health Survey showed overall vaccination rates for NSW and Australia to be more than twice those found for this population.

Self-reported morbidity of Barmah Forest virus infection on the north coast of New South Wales.

OBJECTIVE: To describe the clinical features and disability associated with Barmah Forest virus (BFV) infection. DESIGN: Retrospective postal survey. SETTING: North Coast Public Health Unit, Lismore, New South Wales, January to October 1995. SUBJECTS: All 84 subjects notified by mandatory laboratory reporting as positive for BFV IgM by enzyme-linked immunosorbent assay. OUTCOME MEASURES: Demographic information, self-reported symptoms, disability and treatment. RESULTS: Response rate was 77%. Peak incidence was in the 30-50 years age group, with almost identical numbers of men and women affected. The most common symptoms were lethargy (89%), joint pain (82%) and rash (68%). These were also generally the first symptoms to appear. Thirty of 54 respondents (56%) reported time off work and 27 of 53 (51%) reported illness lasting more than six months. Those who had a rash were significantly more likely to have recovered by the time of the survey than those who had no rash (odds ratio, 10.3; 95% confidence interval, 1.8-76.6). No treatment led to more than slight relief of symptoms. CONCLUSION: Symptoms of BFV infection appear similar to those of the better-known Ross River virus infection, and clinicians should consider both in patients with symptoms of arboviral disease. The wide distribution and long duration of illness make BFV a potentially significant cause of morbidity in Australia. A possible association between the presence of a rash and improved prognosis needs further investigation.

Hepatitis C transmission on the north coast of New South Wales: explaining the unexplained.

OBJECTIVE: To determine the routes of hepatitis C virus (HCV) transmission in an Australian community. DESIGN: Questionnaire-based, cross-sectional survey of notified HCV cases. SUBJECTS AND SETTING: All cases notified to the New South Wales North Coast Public Health Unit between 1 January 1993 and 30 September 1994. OUTCOME MEASURES: Frequency of potential transmission exposures (parenteral and sexual); most likely primary exposure; HCV infection rates in sexual partners and offspring. RESULTS: 467 subjects responded (47% of resident cases). Of these, all but one reported actual or potential blood exposures (injecting drug user [IDU], 85%; IDU with sharing of injection equipment, 76%; pre-1990 blood transfusions, 6%; other blood exposures, 8%). Most subjects reported multiple exposures and none reported sexual contact as the only potential exposure. Of 233 sexual partners tested for HCV, 83 were positive; 54 of these were questioned and all had other parenteral exposures. Only three children out of 91 children tested were positive for HCV (two expressing maternal antibodies). CONCLUSIONS: In contrast with previous studies, possible HCV transmission modes were identified for almost all respondents. Most respondents in this community were IDUs. Non-parenteral transmission appeared minimal. Novel approaches to preventing HCV transmission in IDUs are needed.