Conservation of pro-longevity genes among mammals

Abstract

Genes which confer a relative longevity advantage may be regulated at the level of transcription or translation. Alternatively, pro-longevity genes may mediate their effects at the level of protein structure-functional relationships that are beneficially optimized in long-lived species. Longevity associated genes (LAGs) may be operationally defined as genes that confer beneficial effects and are relatively more conserved among long-lived species. Global and local protein sequence alignments of over 10,000 genes across at least 30 mammalian species were examined to identify LAGs. Known LAGs, including growth hormone receptor (GHR), and breast cancer 1, early onset (BRCA1), have strong associations with maximum lifespan by our analysis. Several common categories of protein function were observed among genes ranked with the strongest associations with MLS identified by all regression models. These genes included those that function in the immune system, cell cycle regulation, and DNA damage response. We provide a ranking of genes with the strongest associations with species maximum lifespan (MLS) by several phylogenetic generalized least squares regression models, including adjustment for confounding variables such as body weight and gestation length.

WITHDRAWN: Temperature-dependent IL6-STAT3-HSP90 signaling mediates viral entry

“…Interestingly, using lentiviral vector based SARS-COV-2 pseudovirus, we found that STAT3 or HSP90 inhibitors treatment blocked the entry of SARS-COV-2 pseudovirus as well, which is consistent with the ndings from other groups showing that the propagation of SARS-COV-2 in host cells is dependent on IL6-STAT3 signaling and HSP90 expression Ulhaq and Soraya, 2020). Together with these observations, our work provides further credence to the pivotal roles of IL6-STAT3-HSP90 signaling axis mediating viral entry, expanding the functional repertoires of IL6 and HSP90 as canonical biomarkers for in ammation, cancer, and aging (Fuhrmann-Stroissnigg et al, 2018;Lindborg et al, 2015;Tanaka et al, 2014;Whitesell and Lindquist, 2005). Furthermore, our data together with recent ndings from other groups suggest that IL6 and HSP90 may serve as risk factors of susceptibility to viral infection Lubkowska et al, 2021;Ulhaq and Soraya, 2020), highlighting the feasibility and rationality of developing targeted therapies towards IL6-STAT3 signaling and HSP90 for viral diseases in the future.…”

Plasma methionine metabolic profile is associated with longevity in mammals

“…However, due to species evolution, interspecies studies have to deal with the problem of non-independence of the data due to evolutionary relationships 71 . Therefore, it is important to elucidate whether a specific trait correlates with longevity differences, or alternatively, these differences arise because of the data similarity, by applying statistical phylogenetic comparative methods, such as PGLS 32 , 72 – 74 , 14 , 23 , 28 , 75 . In the present study, PGLS revealed that pyridoxamine and succinate plasma content changes associated with longevity were not due interspecies relationships.…”

Exceptional Human Longevity

“…Genes for breast cancer 1, early onset, and growth hormone (GH) receptor strongly associate with maximum life span across mammalian species. 57,58 The breast cancer 1, early onset, gene occurs with different genotype frequencies in centenarian populations compared with controls. 59 A GH receptor gene exon 3 deletion alters GH sensitivity, and the prevalence of homozygosity for the exon 3 deletion increases with age in longlived individuals.…”