Polymorphisms associated with type 2 diabetes in familial longevity: The Leiden Longevity Study

Abstract

Human longevity is in part genetically determined, and the insulin/IGF-1 signal transduction (IIS) pathway has consistently been implicated. In humans, type 2 diabetes is a frequent disease that results from loss of glucose homeostasis and for which new candidate polymorphisms now rapidly emerge from genome wide association studies.In the Leiden Longevity Study (n=2415), the offspring of long lived siblings (“offspring”) who are genetically enriched for longevity were shown to have a more beneficial metabolic profile compared to their environmentally matched partners (“controls”), including better glucose tolerance. We tested whether the “offspring” carry a lower burden of diabetes risk alleles. Fifteen polymorphisms derived from genome wide association (GWA) scans in type 2 diabetes were tested for association with parameters of glucose metabolism in offspring and controls, and burden of risk alleles was compared between offspring and controls.Among all participants, a higher number of type 2 diabetes risk alleles associated with a higher prevalence of diabetes (P=0.011) and higher serum concentration of glucose (P<0.016) but not insulin (P=0.450). None of the polymorphisms differed in frequency between the offspring and controls (all P>0.05), nor did the mean total number of risk alleles (P=0.977). The association between polymorphisms and glucose levels did not differ between controls and offspring (Pinteraction=0.523).The better glucose tolerance of the “offspring” is not explained by a lower burden of type 2 diabetes risk alleles, suggesting that specific mechanisms determining longevity exist.

An Intensive Mind and Body Therapeutic Program Leads to Alteration in Gene Expression Critical to Aging Process in Peripheral Blood Stem Cells

“…Furthermore, another critical gene under CMYC pathway such as TMEFF2 [42] (transmembrane protein with EGF-like and two follistatin-like domains 2) was down in the meditated cohort. Genetic variation of TMEFF2 has been shown to affect human longevity [43]. Fourth, in our study P38 MAPK, a key regulator of pro-inflammatory cytokine biosynthesis which induces low-grade chronic inflammation associated with aging was found to be affected by MBT program.…”

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

“…However, adjustment for parental diabetes with onset at any age might lead to an even greater bias because the diagnosis of diabetes is more likely in long-lived than short-lived individuals, and thus parental diabetes with an onset at any age mainly reflects length of life rather than genetic factors. To explain the association between family longevity and prevalence of type 2 diabetes, the frequency of 15 risk alleles known to be related to type 2 diabetes was compared between the offspring of nonagenarian siblings and the offspring's partners in the Leiden Longevity Study [13]. Although the offspring had a better glucose metabolism than their partners, there were no differences in the frequencies of any risk allele, and the mean numbers of risk alleles were virtually identical in both groups.…”

Human Longevity is Influenced by Many Genetic Variants: Evidence from 75,000 UK Biobank Participants

“…There is consistent epidemiological evidence for a relationship between longevity and lower rates of type-2 diabetes [11], yet previous evidence from the Leiden study (n=2415) and the Pilling et al 2016 Biobank longevity genetics Life Long Family Study (n=1562 in generation 1; n=3102 generation 2) suggested that offspring of long-lived participants do not have lower burden of type-2 diabetes risk alleles compared to their partners [10,25]. We also did not observe an association between the type 2 diabetes GRS and longevity in the UK Biobank participants, although small effects cannot be excluded.…”