The maintenance gap: a new theoretical perspective on the evolution of aging

One of the prevailing theories of aging, the disposable soma theory, views aging as the result of the accumulation of damage through imperfect maintenance. Aging, then, is explained from an evolutionary perspective by asserting that this lack of maintenance exists because the required resources are better invested in reproduction. However, the amount of maintenance necessary to prevent aging, ‘maintenance requirement’ has so far been largely neglected and has certainly not been considered from an evolutionary perspective. To our knowledge we are the first to do so, and arrive at the conclusion that all maintenance requirement needs an evolutionary explanation. Increases in maintenance requirement can only be selected for if these are linked with either higher fecundity or better capabilities to cope with environmental challenges to the integrity of the organism. Several observations are suggestive of the latter kind of trade-off, the existence of which leads to the inevitable conclusion that the level of maintenance requirement is in principle unbound. Even the allocation of all available resources to maintenance could be unable to stop aging in some organisms. This has major implications for our understanding of the aging process on both the evolutionary and the mechanistic level. It means that the expected effect of measures to reallocate resources to maintenance from reproduction may be small in some species. We need to have an idea of how much maintenance is necessary in the first place. Our explorations of how natural selection is expected to act on the maintenance requirement provides the first step in understanding this

Supplementary Figures S1 and S2 from Size, longevity and cancer: age structure

There is significant recent interest in Peto's paradox and the related problem of the evolution of large, long-lived organisms in terms of cancer robustness. Peto's paradox refers to the expectation that large, long-lived organisms have a higher lifetime cancer risk, which is not the case: a paradox. This paradox, however, is circular: large, long-lived organisms are large and long-lived <i>because</i> they are cancer robust. Lifetime risk, meanwhile, depends on the age distributions of both cancer and competing risks: if cancer strikes before competing risks, then lifetime risk is high; if not, not. Because no set of competing risks is generally prevalent, it is instructive to temporarily dispose of competing risks and investigate the pure age dynamics of cancer under the multistage model of carcinogenesis. In addition to augmenting earlier results, I show that in terms of cancer-free lifespan large organisms reap greater benefits from an increase in cellular cancer robustness than smaller organisms. Reversely, a higher cellular cancer robustness renders cancer-free lifespan more resilient to an increase in size. This interaction may be an important driver of the evolution of large, cancer robust organisms

Interaction mortality: senescence may have evolved because it increases lifespan.

Given an extrinsic challenge, an organism may die or not depending on how the threat interacts with the organism's physiological state. To date, such interaction mortality has been only a minor factor in theoretical modeling of senescence. We describe a model of interaction mortality that does not involve specific functions, making only modest assumptions. Our model distinguishes explicitly between the physiological state of an organism and potential extrinsic, age-independent threats. The resulting mortality may change with age, depending on whether the organism's state changes with age. We find that depending on the physiological constraints, any outcome, be it 'no senescence' or 'high rate of senescence', can be found in any environment; that the highest optimal rate of senescence emerges for an intermediate physiological constraint, i.e. intermediate strength of trade-off; and that the optimal rate of senescence as a function of the environment is driven by the way the environment changes the effect of the organism's state on mortality. We conclude that knowledge about the environment, physiology and their interaction is necessary before reasonable predictions about the evolution of senescence can be made

Intrinsic and extrinsic mortality reunited

Geriatrics in primary carePublic Health and primary car

Intrinsic and extrinsic mortality reunited

Intrinsic and extrinsic mortality are often separated in order to understand and measure aging. Intrinsicmortality is assumed to be a result of aging and to increase over age,whereas extrinsic mortality is assumed to be a result of environmental hazards and be constant over age. However, allegedly intrinsic and extrinsic mortality have an exponentially increasing age pattern in common. Theories of aging assert that a combination of intrinsic and extrinsic stressors underlies the increasing risk of death. Epidemiological and biological data support that the control of intrinsic as well as extrinsic stressors can alleviate the aging process. We argue that aging and death can be better explained by the interaction of intrinsic and extrinsic stressors than by classifying mortality itself as being either intrinsic or extrinsic. Recognition of the tight interaction between intrinsic and extrinsic stressors in the causation of aging leads to the recognition that aging is not inevitable, but malleable through the environmentWetensch. publicati

The optimal rate of senescence as a function of <i>s</i> for a variety of functions.

<p>The rate of senescence ‘RoS’ calculated as <i>k</i>^*<i>s</i> is given as a function of <i>s</i> for a fixed value of <i>E</i> given three specific trade-off functions. These graphs demonstrate that a variety of patterns may exist, that may have discontinuities and/or points at which the function is not differentiable. Yet these graphs all have in common that the optimal rate of senescence is zero for <i>s</i> = 0, then increases, and then returns to zero for large values of <i>s</i> (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109638#pone.0109638.s001" target="_blank">Appendix S1</a>).</p

The optimal rate of senescence as a function of <i>E</i> for a variety of functions.

<p>The rate of senescence ‘RoS’ calculated as <i>k</i>^*<i>s</i> is given as a function of <i>E</i> for a fixed value of <i>s</i> given three specific trade-off functions. All these functions have in common that a harsher environment allows for a more favorable perturbation of mortality. This, however, may not be the case in general; these simulations are not a general result (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109638#pone.0109638.s001" target="_blank">Appendix S1</a>). Notice how discontinuities can be introduced by changing the function specifics.</p

Elevated CRP levels are associated with increased carotid atherosclerosis independent of visceral obesity

Visceral obesity (VO) is associated with an increased risk of cardiovascular disease. Elevated C-reactive protein (CRP) levels are associated with VO and cardiovascular disease. After exploring the relation between CRP and VO, we aimed to evaluate the VO independent relation between CRP and carotid atherosclerosis. The prevalence of inflammation was evaluated in 439 male subjects with VO without type 2 diabetes and manifest cardiovascular disease. Waist circumference significantly correlated with CRP (r: 0.20, p 118 cm had low CRP levels. From the 439 subjects, 40 subjects were prospectively selected for MRI assessment of carotid atherosclerosis and visceral and subcutaneous adipose tissue distribution in a case-control setting matching for age and waist circumference. Twenty male subjects with age >50 years with CRP levels >2.5mg/L (CRP+) were compared to 20 controls with CRP levels <1.8 mg/L (CRP-). Maximum vessel wall thickness in CRP+ was significantly higher both in the common carotid artery (15%, p <0.01) and the bulb region (18%, p <0.01). The distribution of fat in visceral and subcutaneous deposits was not significantly different between CRP+ and CRP-. Elevated CRP levels are associated with significantly increased maximum vessel wall thickness independent of VO and of MRI measured adipose tissue distribution, both in the common carotid artery and the carotid bul