Generations of longevity

Abstract

The lifespan of some organisms can be extended by mutations that alter how DNA is packaged in their cells. A study reveals that this effect can last for generations, even in descendants that are genetically normal. For decades, ageing was considered to be the result of progressive damage culminating in catastrophic breakdown. Yet similar animals can have vastly different lifespans-a barn owl can expect to live less than 8 years, a parrot more than 30 years-suggesting that there are mutable genetic pathways that control longevity. By studying small animals with short lifespans, such as the roundworm Caenorhabditis elegans, scientists have identified key pathways that can modulate ageing 1. One of these involves the COMPASS complex (most probably an H3K4me3 regulatory complex in C. elegans), an assembly of proteins that organizes DNA by chemically modifying a DNA-packaging protein called histone H3. Mutations in any of the three COMPASS subunits lead to defects in histone regulation and, in C. elegans, to a longer life 2. On page 365 of this issue, Greer et al. 3 show that C. elegans worms have a memory of COMPASS mutations, even when they themselves carry normal, unmutated COMPASS components: great-grand-offspring and even great-great-grand-offspring live longer if their ancestors lacked COMPASS. In classical genetics, heritable changes in an organism's phenotype (its characteristics) that arise independently of DNA mutations are termed epigenetic inheritance, and have been a source of active research as scientists search for the causative mechanism. An attractive idea is that COMPASS generates an unknown molecular cue that can be inherited over multiple generations to restrict longevity. Caenorhabditis elegans is not the only organism to show transgenerational effects in health and longevity. Examples can be found in other animals, including humans, and in plants. One of the earliest reported instances stems from studies in Sweden, where historical records revealed that the nutritional and smoking habits of paternal grandparents could influence their descendants' lifespan 4. In the lab, transient exposure of rats to a high-sugar/low-protein diet leads to glucose intolerance 5 , and exposure of rats to noxious chemicals causes reduced fecundity 6 ; these effects can last for generations 7. Although such transgenerational, epigenetic effects have been documented for multiple species, the mechanism remains a mystery. Greer et al. 3 mated C. elegans worms that bore mutations in COMPASS subunits with wildtype males (Fig.

FNDC5 (irisin) gene and exceptional longevity: a functional replication study with rs16835198 and rs726344 SNPs

“…On the other hand, the role of epigenetic factors in irisinemia remains to be determined. Indeed, epigenetic modifications might also influence longevity by affecting gene expression without changing the DNA sequence (Wolffe and Matzke 1999), i.e., through DNA methylation, histone modifications, and altered expression of RNAs or small, noncoding RNAs that regulate gene expression profiles associated with longevity (Mango 2011).…”

Genetics of Human Longevity Within an Eco-Evolutionary Nature-Nurture Framework

“…The polygenic nature of longevity promoted the idea that larger cohorts are needed to identify the variants, but this approach inevitably causes an increase of the heterogeneity of the cohorts and of environmental confounding factors at the expense of the biology underpinning the trait. Lastly some authors suggested that part of the missing heritability should be searched in non-DNA factors that may be transmitted between generations 15 as important data that connect epigenetic inheritance and longevity from non-human models are emerging [16][17][18][19] . Interestingly analysis and integration of DNA methylation data and RNAseq will be useful tool 20 , but a big effort is still needed to collect data on the same pool of samples 21 .…”

The Biology of Immortality

“…A report on C. elegans found that roundworms with a particular mutation in the H3K4me3 complex that increases their lifespans produced progeny that were similarly long-lived despite not having that mutation [112,113]. How this trait is actually passed on is unclear but may involve epigenetic changes.…”

“…How this trait is actually passed on is unclear but may involve epigenetic changes. Some human studies also suggest transgenerational inheritance-for example, the observation that nutritional and smoking habits in paternal grandparents could influence a person's own lifespan [113].…”