10 August 2023 in Nature Aging
Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.
19 July 2015 in Philosophical Transactions of the Royal Society B: Biological Sciences
Multicellularity is characterized by cooperation among cells for the development, maintenance and reproduction of the multicellular organism. Cancer can be viewed as cheating within this cooperative multicellular system. Complex multicellularity, and the cooperation underlying it, has evolved independently multiple times. We review the existing literature on cancer and cancer-like phenomena across life, not only focusing on complex multicellularity but also reviewing cancer-like phenomena across the tree of life more broadly. We find that cancer is characterized by a breakdown of the central features of cooperation that characterize multicellularity, including cheating in proliferation inhibition, cell death, division of labour, resource allocation and extracellular environment maintenance (which we term the five foundations of multicellularity). Cheating on division of labour, exhibited by a lack of differentiation and disorganized cell masses, has been observed in all forms of multicellularity. This suggests that deregulation of differentiation is a fundamental and universal aspect of carcinogenesis that may be underappreciated in cancer biology. Understanding cancer as a breakdown of multicellular cooperation provides novel insights into cancer hallmarks and suggests a set of assays and biomarkers that can be applied across species and characterize the fundamental requirements for generating a cancer.
1 April 2016 in Trends in Ecology & Evolution
Meiotic drivers are genetic variants that selfishly manipulate the production of gametes to increase their own rate of transmission, often to the detriment of the rest of the genome and the individual that carries them. This genomic conflict potentially occurs whenever a diploid organism produces a haploid stage, and can have profound evolutionary impacts on gametogenesis, fertility, individual behaviour, mating system, population survival, and reproductive isolation. Multiple research teams are developing artificial drive systems for pest control, utilising the transmission advantage of drive to alter or exterminate target species. Here, we review current knowledge of how natural drive systems function, how drivers spread through natural populations, and the factors that limit their invasion.
19 November 2002 in Aging Cell
Summary: The evolutionary theory of aging predicts that life span should decrease in response to the amount of mortality caused by extrinsic sources. Using this prediction, we selected six life history and ecological factors to use in a comparative analysis of longevity among 64 bat species. On average, the maximum recorded life span of a bat is 3.5 times greater than a non‐flying placental mammal of similar size. Records of individuals surviving more than 30 years in the wild now exist for five species. Univariate and multivariate analyses of species data, as well as of phylogenetically independent contrasts obtained using a supertree of Chiroptera, reveal that bat life span significantly increases with hibernation, body mass and occasional cave use, but decreases with reproductive rate and is not influenced by diet, colony size or the source of the record. These results are largely consistent with extrinsic mortality risk acting as a determinant of bat longevity. Nevertheless, the strong association between life span and both reproductive rate and hibernation also suggests that bat longevity is strongly influenced by seasonal allocation of non‐renewable resources to reproduction. We speculate that hibernation may provide a natural example of caloric restriction, which is known to increase longevity in other mammals.
22 February 2013 in Proceedings Of The Royal Society B-Biological Sciences
Common vampire bats often regurgitate food to roost-mates that fail to feed. The original explanation for this costly helping behaviour invoked both direct and indirect fitness benefits. Several authors have since suggested that food sharing is maintained solely by indirect fitness because non-kin food sharing could have resulted from kin recognition errors, indiscriminate altruism within groups, or harassment. To test these alternatives, we examined predictors of food-sharing decisions under controlled conditions of mixed relatedness and equal familiarity. Over a 2 year period, we individually fasted 20 vampire bats (Desmodus rotundus) and induced food sharing on 48 days. Surprisingly, donors initiated food sharing more often than recipients, which is inconsistent with harassment. Food received was the best predictor of food given across dyads, and 8.5 times more important than relatedness. Sixty-four per cent of sharing dyads were unrelated, approaching the 67 per cent expected if nepotism was absent. Consistent with social bonding, the food-sharing network was consistent and correlated with mutual allogrooming. Together with past work, these findings support the hypothesis that food sharing in vampire bats provides mutual direct fitness benefits, and is not explained solely by kin selection or harassment.