Are centenarians genetically predisposed to lower disease risk?

Abstract

Our study purpose was to compare a disease-related polygenic profile that combined a total of 62 genetic variants among (i) people reaching exceptional longevity, i.e., centenarians (n=54, 100-108 years, 48 women) and (ii) ethnically matched healthy controls (n=87, 19-43 years, 47 women). We computed a 'global' genotype score (GS) for 62 genetic variants (mutations/polymorphisms) related to cardiometabolic diseases, cancer or exceptional longevity, and also specific GS for main disease categories (cardiometabolic risk and cancer risk, including 36 and 24 genetic variations, respectively) and for exceptional longevity (7 genetic variants). The 'global' GS was similar among groups (centenarians: 31.0±0.6; controls 32.0±0.5, P=0.263). We observed that the GS for hypertension, cancer (global risk), and other types of cancer was lower in the centenarians group compared with the control group (all P<0.05), yet the difference became non significant after adjusting for sex. We observed significant between-group AGE (2012) 810-13.839), whereas the likelihood of having the GSTMI low-risk (functional) allele was similar in both groups (OR 1.295; 95% CI, 0.868 -1.931). In conclusion, we found preliminary evidence that Spanish centenarians have a lower genetic predisposition for cancer risk. The wild-type (i.e., functional) genotype of GSTT1, which is associated with lower cancer risk, might be associated with exceptional longevity, yet further studies with larger sample sizes must confirm these findings.

Aging: a portrait from gene expression profile in blood cells

“…An important finding of this study is the up-regulation of a group of transcripts encoding for proteins with protective roles against oxidative stress, in support of the free-radical theory of aging [ 26 ] and the notion that successfully managing oxidative stress can help extend lifespan [ 27 ]. In particular, the expression level of GSTM1 has a protective effect, and was associated with reduced mortality in participants of ilSIRENTE study [ 28 ], whereas GSTT1 was associated with lower cancer risk, longevity and aging in human granulosa cells [ 29 ]. Conversely reduced expression of GSTM1 is associated with prostate cancer and leukemia [ 30 ] and its copy number profile is correlated with prognosis [ 31 ].…”

Cancer—Incidence, prevalence and mortality in the oldest-old. A comprehensive review

“…One proposed point of view is that the oldest-old lack the genes that predispose them to chronic diseases (Bonafè et al, 2002;Miyaishi et al, 2000). Literary evidence shows the oldest-old have unique protective genetic variations, which induce a genetic predisposition to prolonged aging, demonstrated by centenarian offspring who survive longer with less health complications (Ruiz et al, 2012;Terry et al, 2004). Polymorphisms of tumor protective genes like tumor protein p53 and the lack of deleterious genes like breast cancer 1 (BRCA1) and transforming protein p21 (HRAS1) in this population may make them cancer resistant (Jeon et al, 2016;Bonafè et al, 2002).…”

The mitochondrial‐derived peptide MOTS‐c: a player in exceptional longevity?

“…Among long‐lived individuals, those who reach exceptional longevity (EL, i.e ., centenarians (≥100 years) and supercentenarians (SCs, ≥110 years)) are arguably the paradigm of successful aging (Andersen et al ., 2012). Several genetic factors might contribute to EL, as suggested by the differences found in the frequency distribution of several genetic variants among centenarians compared with their ethnic‐matched referents of younger ages (Alexe et al ., 2007; Ruiz et al ., 2012; Garatachea et al ., 2014). Factors related to inflammation (Basile et al ., 2012), metabolism (Emanuele et al ., 2014) or nutrition (Pareja‐Galeano et al ., 2015), among others, can also influence the likelihood of reaching EL.…”