PARENTAL LONGEVITY AND THE MULTIPLE PROTECTIVE FACTOR MODEL OF HUMAN AGEING
David Melzer
University of Exeter Medical School (UK) and University of Connecticut Center on Aging (USA)
Offspring of longer lived parents tend to have much better health status, including dramatically lower incidence of cancers, cardiovascular disease and dementia. In our analyses in the Health and Retirement study, with each decade mothers or fathers survived after age 65, all-cause mortality in offspring declined by 19% and 14% per decade respectively: i.e. the health advantage of longer lived parents increased linearly and was not confined to the exceptionally long-lived.
In our analysis of 186,151 non-adopted UK Biobank participants with deceased parents, we found that increasing parental longevity was associated with participant education, higher income, more physical activity, plus lower rates of smoking and obesity. Offspring of longer-lived parents had lower incidence of multiple circulatory conditions including atrial fibrillation and heart failure. For cancer associations were modest except for lung cancer. In our GWAS analysis of 75,000 UKB participants we found three genome significant variants, including a novel DNA repair variant associated with extreme (top 1%) parental survival. We also showed that offspring of longer-lived parents had fewer common genetic risk alleles (lower genetic risk scores) for coronary artery disease, systolic blood pressure, body mass index, cholesterol levels, plus autoimmune conditions and Alzheimer's. Associations were similar for extreme survival, but with an additional association with HDL cholesterol raising variants.
These findings suggest a 'multiple risk and protective factor' model of human aging, influenced by many different pathways. For several pathways, preventive strategies already exist.
David Melzer
University of Exeter Medical School (UK) and University of Connecticut Center on Aging (USA)
Offspring of longer lived parents tend to have much better health status, including dramatically lower incidence of cancers, cardiovascular disease and dementia. In our analyses in the Health and Retirement study, with each decade mothers or fathers survived after age 65, all-cause mortality in offspring declined by 19% and 14% per decade respectively: i.e. the health advantage of longer lived parents increased linearly and was not confined to the exceptionally long-lived.
In our analysis of 186,151 non-adopted UK Biobank participants with deceased parents, we found that increasing parental longevity was associated with participant education, higher income, more physical activity, plus lower rates of smoking and obesity. Offspring of longer-lived parents had lower incidence of multiple circulatory conditions including atrial fibrillation and heart failure. For cancer associations were modest except for lung cancer. In our GWAS analysis of 75,000 UKB participants we found three genome significant variants, including a novel DNA repair variant associated with extreme (top 1%) parental survival. We also showed that offspring of longer-lived parents had fewer common genetic risk alleles (lower genetic risk scores) for coronary artery disease, systolic blood pressure, body mass index, cholesterol levels, plus autoimmune conditions and Alzheimer's. Associations were similar for extreme survival, but with an additional association with HDL cholesterol raising variants.
These findings suggest a 'multiple risk and protective factor' model of human aging, influenced by many different pathways. For several pathways, preventive strategies already exist.
