Is Aging As Complex As It Would Appear?

Kirkwood, Tbl; Franceschi, Claudio

doi:10.1111/j.1749-6632.1992.tb38685.x

Cited by 94 publications

(20 citation statements)

References 14 publications

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“…Evolution theory suggests that aging is caused by a life‐long accumulation of random damage in somatic cells and tissues due to an evolved limitation in the levels of key maintenance functions. This idea, termed the disposable soma theory, predicts a central role for cell maintenance and stress response mechanisms in regulating the duration of life 1–5. There is potentially a large number of such mechanisms, and individual theories have focused, in particular, on the roles of free radicals and oxidative damage, 6–8 aberrant proteins, 9,10 defective mitochondria, 11–13 and somatic mutations 14–17…”

Section: Introductionmentioning

confidence: 99%

“…This idea, termed the disposable soma theory, predicts a central role for cell maintenance and stress response mechanisms in regulating the duration of life. [1][2][3][4][5] There is potentially a large number of such mechanisms, and individual theories have focused, in particular, on the roles of free radicals and oxidative damage, [6][7][8] aberrant proteins, 9,10 defective mitochondria, [11][12][13] and somatic mutations. [14][15][16][17] Two important implications of the disposable soma theory are (1) the need to consider integrated approaches to the study of cell maintenance, and (2) the explicit prediction that the mechanisms of cell aging are intrinsically stochastic.…”

Section: Introductionmentioning

confidence: 99%

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Molecular Gerontology: Bridging the Simple and the Complex

Kirkwood

2000

Annals of the New York Academy of Sciences

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It is clear, both empirically and theoretically, that the mechanisms of aging are multiple and complex. Nevertheless, single gene mutations and simple interventions such as calorie restriction have broad effects on the senescent phenotype. The major challenge is to unite highly reductionist analysis of molecular components with integrative model systems that can “put it all together.” Two themes are developed. In the first, biochemical models are described that show how the network concept of cellular aging can be used to integrate multiple biochemical mechanisms that contribute to cellular instability. In the second theme, the role of intrinsic developmental chance is examined as a major factor contributing, in addition to genes and environment, to the divergence of the senescent phenotype. The implications of these themes for research strategies in molecular gerontology are discussed.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Molecular Gerontology: Bridging the Simple and the Complex

Kirkwood

2000

Annals of the New York Academy of Sciences

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“…This concept leads to a number of testable predictions (Kirkwood & Franceschi, 1992). First, ageing is not programmed in the sense that there exists any active mechanism to cause death.…”

Section: mentioning

confidence: 99%

Evolution, stress, and longevity

2000

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The disposable soma theory suggests that longevity is determined through the setting of longevity assurance mechanisms so as to provide an optimal compromise between investments in somatic maintenance (including stress resistance) and in reproduction. A corollary is that species with low extrinsic mortality are predicted to invest relatively more effort in maintenance, resulting in slower intrinsic ageing, than species with high extrinsic mortality. We tested this prediction in a comparative study of stress resistance in primary skin fibroblasts and confirmed that cells from long-lived species are indeed more resistant to a variant of stressors. A widely studied example of within-species variation in lifespan is the rodent calorie restriction model. Food-restricted animals show elevations in a range of stress response mechanisms, and it has been suggested that this is an outcome of natural selection for life history plasticity. We have developed a theoretical model for dynamic optimisation of the allocation of effort to maintenance and reproduction in response to fluctuations in food availability. The model supports the suggestion that the response to calorie restriction may be an evolutionary adaptation, raising interesting questions about the hierarchy of genetic control of multiple stress response systems. The model identifies ecological factors likely to support such an adaptation that may be relevant in considering the likely relevance of a similar response to calorie restriction in other species. Comparative and theoretical studies support the role of somatic maintenance and stress response systems in controlling the rate of ageing.

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“…If the innate immune system is unsuccessful in eliminating the stimulus or stressor that is antigenic, it induces and recruits cells of the adaptive immune response (Supplemental Figure 3). Thus, a principal alteration responsible for immunosenescence is the overall decline of antigen-specific immunity due to a loss of numbers of naïve and regulatory T lymphocytes [29, 89–91] and reduced generation of progenitor B cells in the bone marrow [90, 92]. T cells from aged individuals display decreased to T cell receptor (TCR) stimulation [93, 94], and altered cytokine profiles that reduce B cell helper functions [94],.…”

Section: Aging and Adaptive Immune Responsesmentioning

confidence: 99%

Age and Periodontal Health—Immunological View

Ebersole

Dawson

Huja

et al. 2018

Curr Oral Health Rep

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Purpose of the Review: Aging clearly impacts a wide array of systems, in particular the breadth of the immune system leading to immunosenescence, altered immunoactivation, and coincident inflammaging processes. The net result of these changes leads to increased susceptibility to infections, increased neoplastic occurrences, and elevated frequency of autoimmune diseases with aging. However, as the bacteria in the oral microbiome that contribute to the chronic infection of periodontitis is acquired earlier in life, the characteristics of the innate and adaptive immune systems to regulate these members of the autochthonous microbiota across the lifespan remains ill defined. Recent Findings: Clear data demonstrate that both cells and molecules of the innate and adaptive immune response are adversely impacted by aging, including in the oral cavity, yielding a reasonable tenet that the increased periodontitis noted in aging populations is reflective of the age-associated immune dysregulation. Additionally, this facet of host-microbe interactions and disease needs to accommodate the population variation in disease onset and progression, which may also reflect an accumulation of environmental stressors and/or decreased protective nutrients that could function at the gene level (ie. epigenetic) or translational level for production and secretion of immune system molecules. Summary: Finally, the majority of studies of aging and periodontitis have emphasized the increased prevalence/severity of disease with aging, all based upon chronological age. However, evolving areas of study focusing on “biological aging” to help account for population variation in disease expression, may suggest that chronic periodontitis represents a co-morbidity that contributes to “gerovulnerability” within the population.

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Is Aging As Complex As It Would Appear?

Cited by 94 publications

References 14 publications

Molecular Gerontology: Bridging the Simple and the Complex

Molecular Gerontology: Bridging the Simple and the Complex

Evolution, stress, and longevity

Age and Periodontal Health—Immunological View

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