Association of Polymorphisms in Connective Tissue Growth Factor and Epidermal Growth Factor Receptor Genes With Human Longevity

Abstract

Growth pathways play key roles in longevity. The present study tested single-nucleotide polymorphisms (SNPs) in the connective tissue growth factor gene (CTGF) and the epidermal growth factor receptor gene (EGFR) for association with longevity. Comparison of allele and genotype frequencies of 12 CTGF SNPs and 41 EGFR SNPs between 440 American men of Japanese ancestry aged ≥95 years and 374 men of average life span revealed association with longevity at the p < .05 level for 2 SNPs in CTGF and 7 in EGFR. Two in CTGF and two in EGFR remained significant after Bonferroni correction. The SNPs of both CTGF and EGFR were in a haplotype block in each respective gene. Haplotype analysis confirmed the suggestive association found by χ2 analysis. We noted an excess of heterozygotes among the longevity cases, consistent with heterozygote advantage in living to extreme old age. No associations of the most significant SNPs were observed in whites or Koreans. In conclusion, the present findings indicate that genetic variation in CTGF and EGFR may contribute to the attainment of extreme old age in Japanese. More research is needed to confirm that genetic variation in CTGF and EGFR contributes to the attainment of extreme old age across human populations.

Lifespan extension conferred by mitogen-activated protein kinase kinase kinase 5 (MAP3K5) longevity-associated gene variation is confined to at-risk men with a cardiometabolic disease

“…This finding adds to our recent findings of a similar explanation for the longevity association conferred by particular SNPs in FOXO3 [ 17 ] and PIK3R5 [ 18 ]. The effect does not, however, explain the longevity association we have found for most other genes in our cohort of elderly men [ 7 , 19 ] (unpublished).…”

Royal Jelly and Its Components Promote Healthy Aging and Longevity: From Animal Models to Humans

“…In humans, women live longer than men, yet they have higher genetic risk for some age-related diseases (e.g., Alzheimer’s disease) than men, which indicates the possibility for gender-specific treatment targets [128]. Other types of genetic variation are also important; for instance, RJ affects the EGFR pathway, which has been shown to be associated with prolonged lifespan in Japanese—but not in whites or Koreans—which highlights a role of ethnic difference in genotype and epigenotype [101]. Other factors, such as other genetic variation factors, diet, and activity level (which affects healthspan and longevity) should be considered in future clinical trials.…”

“…The role of lowered insulin signaling/insulin-like growth factor-1 pathway ( IIS ) in longevity is well documented [101,102]. Findings from studies of C. elegans show that IIS does not only contribute to prolonged of lifespan, but it also promotes healthspan by resisting different types of stress [102].…”

“…In humans, a recent study tested single-nucleotide polymorphisms ( SNPs ) in EGFR for association with longevity. Comparison of genotype frequencies of 41 EGFR SNPs between 440 American males of Japanese ancestry aged ≥95 years and 374 men of average lifespan (whites and Koreans) revealed a significant association with longevity for seven SNPs in EGFR —evidence that genetic variation in EGFR contributes to lifespan extension in Japanese people [101].…”

Age-related but not longevity-related genes are found by weighted gene co-expression network analysis in the peripheral blood cells of humans

“…Thus, researchers have strived to identify genetic differences between long-lived and average-lived individuals. Numerous candidate longevity genes, such as CTGF, EGFR,FOXO3A,APOE,SIRT1,were discovered (Deelen et al, 2013;Li et al, 2016a;Donlon et al, 2017). However, only several of them can be replicated (Broer et al, 2015;Dato et al, 2017), and different outcomes were observed in different studies (Li et al, 2016b;Lin et al, 2016a), indicating that candidate genes may not be highly specific to longevity.…”