The evolution of aging: a new approach to an old problem of biology

Bowles, Josephine

doi:10.1016/s0306-9877(98)90079-2

Cited by 70 publications

(34 citation statements)

References 142 publications

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“…Bowles, 1998;Gerhold et al, 2005). In this respect, common molecular machinery that results in ageing may occur throughout eukaryotes and the reduction in cAMP accumulation in the sectors suggests a new area for research on fungal ageing.…”

Section: Discussionmentioning

confidence: 99%

Colony sectorization of Metarhizium anisopliae is a sign of ageing

2005

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Spontaneous phenotypic degeneration resulting in sterile sectors is frequently observed when culturing filamentous fungi on artificial medium. Sterile sectors from two different strains of the insect pathogenic fungus Metarhizium anisopliae were investigated and found to contain reduced levels of cAMP and destruxins (insecticidal peptides). Microarray analysis using slides printed with 1730 clones showed that compared to wild-type, sterile sectors down-regulated 759 genes and upregulated 27 genes during growth in Sabouraud glucose broth or on insect cuticle. The differentially expressed genes are largely involved in cell metabolism (18?8 %), cell structure and function (13?6 %) and protein metabolism (8?8 %). Strong oxidative stress was demonstrated in sectorial cultures using the nitro blue tetrazolium assay and these cultures show other syndromes associated with ageing, including mitochondrial DNA alterations. However, genes involved in deoxidation and self-protection (e.g. heat-shock proteins, HSPs) were also upregulated. Further evidence of physiological adaptation by the degenerative sectorial cultures included cell-structure reorganization and the employment of additional signalling pathways. In spite of their very similar appearance, microarray analysis identified 181 genes differentially expressed between the two sectors, and the addition of exogenous cAMP only restored conidiation in one of them. Most of the differentially expressed genes were involved in catabolic or anabolic pathways, but the latter included genes for sporulation. Compared to the mammalian ageing process, sectorization in M. anisopliae showed many similarities, including similar patterns of cAMP production, oxidative stress responses and the involvement of HSPs. Thus, a common molecular machinery for ageing may exist throughout the eukaryotes. INTRODUCTIONThe ascomycete Metarhizium anisopliae is a widespread, soil-borne pathogen of insects, ticks and mites (Roberts & St Leger, 2004). Strains of this fungus are being developed for the control of pest species (Butt et al., 2001). Like many other fungi (Morrow et al., 1989;Kale & Bennett, 1992;Li et al., 1994), it frequently shows culture degeneration (sterile sectorization): a loss or reduction in sporulation and virulence with a fluffy-mycelium type growth. Fungal culture degeneration is usually irreversible and inheritable, and can result in great commercial losses (Li et al., 1994;Horgen et al., 1996;Ryan et al., 2003).Apart from the reports of secondary metabolite decline in degenerative fungal cultures (Wing et al., 1995; Guzman-dePena & Ruiz-Herrera, 1997;Ryan et al., 2002; Kale et al., 2003), little information is available to explain fungal culture instability at the molecular level. However, genomic DNA methylation was reported in a sector of Fusarium oxysporum after successive subculturing (Kim, 1997). In another case, fungal morphological instability was linked to dsRNA virus infection (Dawe & Nuss, 2001).In this study, the spontaneous sterile sectors from two genetically di...

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Section: Discussionmentioning

confidence: 99%

Colony sectorization of Metarhizium anisopliae is a sign of ageing

2005

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“…Human aging involves a series of chronological processes including shortening of telomeres of the chromosomes, mitochondrial aging, accumulation of mutations, and expression of genes of aging, among others (Bowles 1998).…”

Section: Introductionmentioning

confidence: 99%

Adrenopause or decline of serum adrenal androgens with age in women living at sea level or at high altitude

Gonzales¹,

Góñez²,

Villena³

2002

Journal of Endocrinology

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The present study aimed to determine adrenopause or reduction of serum adrenal androgens with age at high altitude and at sea level. It was a cross-sectional study performed in 210 women resident at high altitude (4340 m) and 123 women living in Lima (150 m), aged 20-70 years. Fasting early morning blood samples were obtained. Serum dehydroepiandrosterone (DHEA), DHEA sulphate (DHEAS), androstenedione, testosterone and estradiol were measured by radioimmunoassay. Serum testosterone concentrations were greater in women living at high altitude than in those resident at sea level. Serum concentrations of DHEA, DHEAS and androstenedione were lower in women living at high altitude than in those living at sea level. The DHEAS/DHEA ratio was significantly greater, and the androstenedione/testosterone ratio was lower in samples from women living at high altitude. Among women older than 50 years of age, a greater decline in serum concentrations of DHEA was observed in those living at high altitude than in those living at sea level. Among women 60-70 years of age, serum concentrations of DHEA at high altitude were 46·9% of those in women of the same age living at sea level. Decay of DHEAS at sea level and at high altitude occurred from the age of 40 years. The decline was faster at high altitude than at sea level, and in women aged 60-70 years serum values of DHEAS at high altitude were 56% of those at sea level. In the same age group, serum concentrations of androstenedione among those native to high altitudes were 27·34% of the value at sea level. At sea level, serum testosterone concentrations did not change with age from 20 to 70 years. In women aged 20-39 years and 50-59 years, serum testosterone concentrations were greater at high altitude than at sea level (P<0·05). In those aged 60-70 years, the concentrations were similar in those living at sea level and at high altitude. At sea level and at high altitude, the serum testosterone/estradiol ratio increased with age (P<0·0034 and P<0·0001 respectively). This ratio increased at an earlier age among those living at high altitude (40-49 years) than among those living at sea level (50-59 years). Multivariate analysis showed that altitude (P<0·0001) and greater chronological age (P<0·001) were associated with lower serum DHEAS concentrations. DHEAS was related to chronological age (P<0·0001). Low serum androstenedione concentrations were related to living at high altitude at birth and greater chronological age (P<0·0001). In conclusion, adrenopause is attained earlier and is of greater magnitude at high altitude than at sea level.

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“…Others who have advocated this position explicitly include Skulachev [21], Bredesen [22], Goldsmith [23], Longo [24], Clark [25], Travis [26], Martins [27], Libertini [28] and Bowles [29]. Kenyon and Barja have indicated to me privately that sections of their submitted articles concerning programmed aging have been deleted by peer reviewers as a condition of publication.…”

Section: Reasons To Believe In An Aging Clockmentioning

confidence: 99%

“…And yet there is evidence that senescing cells are characterized by progressive demethylation, so that chromosomes in younger cells tend to be more methylated than older cells [84,85]. The possibility that demethylation may be an aging clock was first proposed by Bowles [29], based on the fact that 'aging is accompanied by DNA demethylation [86][87][88]. In fact, the animal genome loses practically all 5-methylcytosines during the life, the rate of the loss being inversely proportional to maximal lifespan of the species [88].…”

Section: Epigenetic Clock Hypothesismentioning

confidence: 99%

How Does the Body Know How Old It Is? Introducing the Epigenetic Clock Hypothesis

Mitteldorf

2014

Interdisciplinary Topics in Gerontology and Geriatrics

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Animals and plants have biological clocks that help to regulate circadian cycles, seasonal rhythms, growth, development and sexual maturity. If aging is not a stochastic process of attrition but is centrally orchestrated, it is reasonable to suspect that the timing of senescence is also influenced by one or more biological clocks. Evolutionary reasoning first articulated by G. Williams suggests that multiple, redundant clocks might influence organismal aging. Some aging clocks that have been proposed include the suprachiasmatic nucleus, the hypothalamus, involution of the thymus, and cellular senescence. Cellular senescence, mediated by telomere attrition, is in a class by itself, having recently been validated as a primary regulator of aging. Gene expression is known to change in characteristic ways with age, and in particular DNA methylation changes in age-related ways. Herein, I propose a new candidate for an aging clock, based on epigenetics and the state of chromosome methylation, particularly in stem cells. If validated, this mechanism would present a challenging but not impossible target for medical intervention.

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The evolution of aging: a new approach to an old problem of biology

Cited by 70 publications

References 142 publications

Colony sectorization of Metarhizium anisopliae is a sign of ageing

Colony sectorization of Metarhizium anisopliae is a sign of ageing

Adrenopause or decline of serum adrenal androgens with age in women living at sea level or at high altitude

How Does the Body Know How Old It Is? Introducing the Epigenetic Clock Hypothesis

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