Genes and life-style factors in BELFAST nonagenarians: Nature, Nurture and Narrative

Abstract

Understanding how to ‘Age Longer and Age Well’ is a priority for people personally, for populations globally and for government policy. Nonagenarians are the oldest members of our societies and survivors of their generation. Approximately 10 % of nonagenarians reach 90 years and beyond in good condition and seem to have a combination of both age-span and health-span. But what are the factors which help people reach their ninetieth birthday and beyond in good condition? Are they genetics, as in ‘nature’, or do they depend on ‘nurture’ and are related to environment, or are both factors inextricably intertwined within the concept of behavioural genetics? Nonagenarians have rich life experiences that can teach us much about ageing well; they are reservoirs of genetic, life-style and behavioural information which can help dissect out how to live not only longer but better. Personal family history and narrative are powerful tools that help to determine familial traits, beliefs and social behaviours and when used in parallel with new biotechnology methods inform and elaborate causality. Here we present themes and insights from personal narrative enquiry from nonagenarian participants from the Belfast Elderly Longitudinal Free-living Ageing STudy (BELFAST) about factors they consider important for good quality ageing and relate these insights to the emerging genetics and life-style evidence associated with healthy longevity.

Living long and ageing well: is epigenomics the missing link between nature and nurture?

“…Subjects willing to enrol, were community-living, mobile, and mentally competent (Mini Mental Score Examination [26/30), (Folstein et al 1975) and gave written consent. Briefly, subjects gave blood samples for DNA and other laboratory variables, responded to nutrition, life style and medical history questionnaires, blood pressure and anthropometric measurements (Rea et al 2009) and provided self-directed narrative life-stories (Ganzevoort and Bouwer 2007) together with structured questions (Rea and Rea 2011;Rea et al 2015). Ethical permission for the Belfast Elderly Longitudinal Free-Living Ageing STudy (BELFAST) studies was given by Research Ethics Committee Northern Ireland (ORECNI), 08/NIR03/42 and by The Queens University Belfast.…”

Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines

“…Aging is heterogeneous among people and highly variable between different organs and tissues. Our genes, our lifestyles, and our response to stress are infinitely individual and variable, so that the immunobiography of each life tells a different story of how each will respond to the internal and external environmental stressors ( 1 – 3 , 384 ). But evidence is accumulating that the aging process may be malleable.…”

“…The inflammatory response must be tightly regulated to ensure effective immune protection. It is a dynamic network that is continuously remodeling throughout each person’s life as a result of the interaction between our genes, lifestyles, and environments ( 1 – 3 ). Infections and tissue damage from the external environment and our personal internal response to stress can act as triggers to initiate the inflammatory defense response.…”

Genetic interplay between human longevity and metabolic pathways — a large‐scale eQTL study

“…On the genetic level, nonagenarians and centenarians have been hypothesized to harbor specific alleles with protective effects, so‐called longevity variants, that may buffer or counteract the numerous disease variants they carry (Bergman et al ., ; Beekman et al ., ; Sebastiani et al ., ). However, so far, variation in only three loci, the APOE gene (Schächter et al ., ; Rea et al ., ), the FOXO3A gene in the insulin‐IGF1 pathway (Willcox et al ., ; Flachsbart et al ., ; Soerensen et al ., ), and a region of unknown function on chromosome 5q33.3 (Deelen et al ., ), has been reported to influence survival beyond 90 years of age in various populations. Many more genes are assumed to play a role in human longevity, but they have remained undetected as yet despite large‐scale genome‐wide efforts (Deelen et al ., , ; Nebel et al ., ; Beekman et al ., ).…”