During exponential growth some cells of E. coli undergo senescence mediated by asymmetric segregation of damaged components, particularly protein aggregates. We showed previously that functional cell ...division asymmetry in E. coli was responsive to the nutritional environment. Short term exposure as well as long term selection in low calorie environments led to greater cell division symmetry and decreased frequency of senescent cells as compared to high calorie environments. We show here that long term selection in low nutrient environment decreased protein aggregation as revealed by fluorescence microscopy and proportion of insoluble proteins. Across selection lines protein aggregation was correlated significantly positively with the RNA content, presumably indicating metabolic rate. This suggests that the effects of caloric restriction on cell division symmetry and aging in E. coli may work via altered protein handling mechanisms. The demonstrable effects of long term selection on protein aggregation suggest that protein aggregation is an evolvable phenomenon rather than being a passive inevitable process. The aggregated proteins progressively disappeared on facing starvation indicating degradation and recycling demonstrating that protein aggregation is a reversible process in E. coli.
In host–parasite co-evolution, parasites are assumed to have an advantage owing to their shorter generation time. Evolution of pathogens within the lifetime of a host individual is implicated as a ...strong selective force in the evolution of sex and aging in the host. However, this assumption or its testable predictions have not been examined empirically. We classified infectious bacteria and viruses into those that can have continued long-term existence on the host body (group 1) versus those that have only a short-term interaction during an active infection (group 2). We surveyed the literature for age-specific incidence data about infections from both the groups. The age trends of the two groups show contrasting patterns. The incidence of infections by all group 1 pathogens showed a 2.28- to 28-fold increase in older ages. In group 2, 6 out of the 9 pathogens showed a significant declining trend in incidence with age. In both groups, there was greater mortality or morbidity among the infected in the old-age classes. These patterns are better explained by pathogen evolution than by age-related decline in immunity.
Aging has been demonstrated in unicellular organisms and is presumably due to asymmetric distribution of damaged proteins and other components during cell division. Whether the asymmetry-induced ...aging is inevitable or an adaptive and adaptable response is debated. Although asymmetric division leads to aging and death of some cells, it increases the effective growth rate of the population as shown by theoretical and empirical studies. Mathematical models predict on the other hand, that if the cells divide symmetrically, cellular aging may be delayed or absent, growth rate will be reduced but growth yield will increase at optimum repair rates. Therefore in nutritionally dilute (oligotrophic) environments, where growth yield may be more critical for survival, symmetric division may get selected. These predictions have not been empirically tested so far. We report here that Escherichia coli grown in oligotrophic environments had greater morphological and functional symmetry in cell division. Both phenotypic plasticity and genetic selection appeared to shape cell division time asymmetry but plasticity was lost on prolonged selection. Lineages selected on high nutrient concentration showed greater frequency of presumably old or dead cells. Further, there was a negative correlation between cell division time asymmetry and growth yield but there was no significant correlation between asymmetry and growth rate. The results suggest that cellular aging driven by asymmetric division may not be hardwired but shows substantial plasticity as well as evolvability in response to the nutritional environment.
Phylogenetic diversity of culturable actinobacteria isolated from the intertidal regions of west coast of Maharashtra, India was studied using 16S rRNA gene sequencing. Total of 140 actinobacterial ...isolates were obtained, which belonged to 14 genera, 10 families and 65 putative species with
Streptomyces
being the most dominant (63%) genus followed by
Nocardiopsis
and
Micromonospora
. Isolates were screened for production of extracellular protease inhibitors (PI) against three pure proteases viz. chymotrypsin, trypsin, subtilisin and a crude extracellular protease from
Pseudomonas aeruginosa
. Eighty percent of the isolates showed PI activity against at least one of the four proteases, majority of these belonged to genus
Streptomyces
. Actinobacterial diversity from two sites Ade (17° 52′ N, 73° 04′ E) and Harnai (17° 48′ N, 73° 05′ E) with varying anthropological pressure showed that more putative species diversity was obtained from site with lower human intervention i.e. Ade (Shannon’s H 3.45) than from Harnai (Shannon’s H 2.83), a site with more human intervention. However, in Ade, percentage of isolates not showing PI activity against any of the proteases was close to 21% and that in Harnai was close to 9%. In other words, percentage of PI producers was lower at a site with lesser human intervention.
Several unresolved issues, paradoxes, and information voids characterize the field of evolution of aging. The recent discovery of aging-like phenomenon inEscherichia coli, marked by asymmetric ...segregation of damaged components, particularly protein aggregates, has created a number of new possibilities that remain underexplored. Bacterial systems can potentially throw light on issues such as: whether evolution of aging and evolution of death are different phenomena; whether aging is inevitable for life or is an evolved strategy; whether there could be selection for aging or aging is a pleiotropic effect of some other selection; what are the possible mechanisms of antagonistic pleiotropy, if any; and whether there are mechanisms of aging that are conserved throughout the hierarchy of life. Bacterial aging itself is underexplored and least understood as of now, but even scratching the surface appears to reveal things that may compel us to revise some of the classical concepts about evolution of aging. This warrants more focused and innovative inquiry into aging-like processes in bacteria.
Obesity and related disorders are thought to have their roots in metabolic “thriftiness” that evolved to combat periodic starvation. The association of low birth weight with obesity in later life ...caused a shift in the concept from thrifty gene to thrifty phenotype or anticipatory fetal programming. The assumption of thriftiness is implicit in obesity research. We examine here, with the help of a mathematical model, the conditions for evolution of thrifty genes or fetal programming for thriftiness. The model suggests that a thrifty gene cannot exist in a stable polymorphic state in a population. The conditions for evolution of thrifty fetal programming are restricted if the correlation between intrauterine and lifetime conditions is poor. Such a correlation is not observed in natural courses of famine. If there is fetal programming for thriftiness, it could have evolved in anticipation of social factors affecting nutrition that can result in a positive correlation.
Out of the multiple interpretations of cancers, two predominant ones have been (i) somatic evolution of cheater cells that escape replication regulation and (ii) cancers as non-healing wounds. Both ...the interpretations have substantial support as well as glaring anomalies but the two along with other possible interpretations have not been put together to make a coherent synthesis. We argue here that mechanisms and pathways to escape the normal regulation of cell proliferation do not need to evolve _de novo_. Mechanisms to override the normal regulation have already evolved for wound healing and tissue regeneration. Almost all of the hallmarks of cancer are also seen in the wound healing process. This suggests that cancer develops not by any _de novo_ gain of function but by exaptation of pre-evolved wound healing functions. Somatic evolution that makes the wound healing triggers constitutive is not mutation limited but selection limited and the selective forces are dependent on the tissue microenvironment. Some mechanisms for such selection have been suggested. Many more need to be investigated. A series of mechanisms have evolved to minimize the risk of cancers which may fail in an altered lifestyle context. We support our synthesis with multiple lines of evidence and also make differential testable predictions. This evolutionary perspective challenges multiple prevalent ideas, suggests novel lines of research and also has translatable implications for cancer prevention.
Cancers have been interpreted either as somatic evolution of cheater cells that escape replication regulation or alternatively as non-healing wounds. Both the interpretations have substantial support ...as well as glaring anomalies but the two have not been put together to make a coherent synthesis. We argue here that mechanisms and pathways to escape the normal regulation of cell proliferation do not need to evolve de novo. Mechanisms to override the normal regulation have already evolved for wound healing and tissue regeneration. Almost all of the hallmarks of cancer are also seen in the wound healing process. This suggests that cancer develops not by any de novo gain of function but by exaptation of pre-evolved wound healing functions. Somatic evolution that makes the wound healing triggers constitutive is not mutation limited but selection limited and the selective forces are dependent on the tissue microenvironment. Some mechanisms for such selection have been suggested. Many more need to be investigated. A series of mechanisms have evolved to minimize the risk of cancers which may fail in an altered lifestyle context. We support our synthesis with multiple lines of evidence and also make differential testable predictions. This evolutionary perspective challenges multiple prevalent ideas, suggests novel lines of research and also has translatable implications for cancer prevention.
Abstract
A very fundamental paradox of insulin resistance is that in a wide variety of animal models impairment of insulin signaling increases life span. But in humans it increases the risk of a ...range of fatal disorders. The Klotho protein appears to resolve this paradox. Overexpression of the Klotho gene increases longevity in mammals by inducing insulin resistance. But the Klotho protein is simultaneously anti-inflammatory, antioxidant and pro-angiogenesis. A number of other studies have indicated that systemic inflammation, angiogenesis dysfunction and oxidative stress are the main causes of pathological complications of diabetes. The Klotho protein has demonstrated that insulin resistance can be decoupled from these pathogenic mechanisms and if decoupled it might contribute to longevity in humans as well. However, insulin resistance has always been treated as the therapeutic target for type 2 diabetes. Our hypothesis suggests that therapy for type 2 diabetes should deviate from insulin resistance and focus on normalizing angiogenic, inflammatory and oxidative mechanisms.
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