Long-range correlations and fractal dynamics in C. elegans: changes with aging and stress

Reduced motor control is one of the most frequent features associated with aging and disease. Nonlinear and fractal analyses have proved to be useful in investigating human physiological alterations with age and disease. Similar findings have not been established for any of the model organisms typically studied by biologists, though. If the physiology of a simpler model organism displays the same characteristics, this fact would open a new research window on the control mechanisms that organisms use to regulate physiological processes during aging and stress. Here, we use a recently introduced animal tracking technology to simultaneously follow tens of Caenorhabdits elegans for several hours and use tools from fractal physiology to quantitatively evaluate the effects of aging and temperature stress on nematode motility. Similarly to human physiological signals, scaling analysis reveals long-range correlations in numerous motility variables, fractal properties in behavioral shifts, and fluctuation dynamics over a wide range of timescales. These properties change as a result of a superposition of age and stress-related adaptive mechanisms that regulate motility.Comment: Accepted for publication in Physical Review

Age structure landscapes emerge from the equilibrium between aging and rejuvenation in bacterial populations.

The physiological asymmetry between daughters of a mother bacterium is produced by the inheritance of either old poles, carrying non-genetic damage, or newly synthesized poles. However, as bacteria display long-term growth stability leading to physiological immortality, there is controversy on whether asymmetry corresponds to aging. Here we show that deterministic age structure landscapes emerge from physiologically immortal bacterial lineages. Through single-cell microscopy and microfluidic techniques, we demonstrate that aging and rejuvenating bacterial lineages reach two distinct states of growth equilibria. These equilibria display stabilizing properties, which we quantified according to the compensatory trajectories of continuous lineages throughout generations. Finally, we show that the physiological asymmetry between aging and rejuvenating lineages produces complex age structure landscapes, resulting in a deterministic phenotypic heterogeneity that is neither an artifact of starvation nor a product of extrinsic damage. These findings indicate that physiological immortality and cellular aging can both be manifested in single celled organisms

Cell aging preserves cellular immortality in the presence of lethal levels of damage.

Cellular aging, a progressive functional decline driven by damage accumulation, often culminates in the mortality of a cell lineage. Certain lineages, however, are able to sustain long-lasting immortality, as prominently exemplified by stem cells. Here, we show that Escherichia coli cell lineages exhibit comparable patterns of mortality and immortality. Through single-cell microscopy and microfluidic techniques, we find that these patterns are explained by the dynamics of damage accumulation and asymmetric partitioning between daughter cells. At low damage accumulation rates, both aging and rejuvenating lineages retain immortality by reaching their respective states of physiological equilibrium. We show that both asymmetry and equilibrium are present in repair mutants lacking certain repair chaperones, suggesting that intact repair capacity is not essential for immortal proliferation. We show that this growth equilibrium, however, is displaced by extrinsic damage in a dosage-dependent response. Moreover, we demonstrate that aging lineages become mortal when damage accumulation rates surpass a threshold, whereas rejuvenating lineages within the same population remain immortal. Thus, the processes of damage accumulation and partitioning through asymmetric cell division are essential in the determination of proliferative mortality and immortality in bacterial populations. This study provides further evidence for the characterization of cellular aging as a general process, affecting prokaryotes and eukaryotes alike and according to similar evolutionary constraints

Declines in swimming performance with age: a longitudinal study of Masters swimming champions.

IntroductionBecause of its many participants and thorough records, competitive Masters swimming offers a rich data source for determining the rate of physical decline associated with aging in physically fit individuals. The decline in performance among national champion swimmers, both men and women and in short and long swims, is linear, at about 0.6% per year up to age 70-75, after which it accelerates in quadratic fashion. These conclusions are based primarily on cross-sectional studies, and little is known about individual performance declines with aging. Herein we present performance profiles of 19 male and 26 female national and international champion Masters swimmers, ages 25 to 96 years, participating in competitions for an average of 23 years.Methods and resultsSwimmers' longitudinal data were compared with the fastest times of world record holders across ages 35-100 years by two regression methods. Neither method proved to accurately model this data set: compared with the rates of decline estimated from the world record data, which represent the best recorded times at given ages, there was bias toward shallower rates of performance decline in the longitudinal data, likely owing to a practice effect in some swimmers as they began their Masters programs. In swimmers' later years, once maximum performance had been achieved, individual profiles followed the decline represented in the world records, and a few swimmers became the world record holders. In some instances, the individual profiles indicated performance better than the world record data; these swimmers achieved their times after the world record data were collected in 2005-2006.ConclusionDeclining physiological functional capacity occurs with advancing age, and this is reflected in the performance decrements of aging Masters swimmers. Individual swimmers show different performance trajectories with aging, declines being mitigated by practice, which improves both physiological capacity and swimming technique, particularly in the early years of participation. The longitudinal data of this study indicate that individuals can participate in high-intensity swimming over several decades, competitively improving over those decades until, in some instances, they become world record holders for their age groups

A comparison of melatonin and α-lipoic acid in the induction of antioxidant defences in L6 rat skeletal muscle cells.

Aging is characterized by a progressive deterioration in physiological functions and metabolic processes. The loss of cells during aging in vital tissues and organs is related to several factors including oxidative stress and inflammation. Skeletal muscle degeneration is common in elderly people; in fact, this tissue is particularly vulnerable to oxidative stress since it requires large amounts of oxygen, and thus, oxidative damage is abundant and accumulates with increasing age. Melatonin (N-acetyl-5-methoxytryptamine) is a highly efficient scavenger of reactive oxygen species and it also exhibits beneficial anti-inflammatory and anti-aging effects. This study investigated the susceptibility of rat L6 skeletal muscle cells to an induced oxidative stress following their exposure to hydrogen peroxide (50 μM) and evaluating the potential protective effects of pre-treatment with melatonin (10 nM) compared to the known beneficial effect of alpha-lipoic acid (300 μM). Hydrogen peroxide-induced obvious oxidative stress; it increased the expression of tumour necrosis factor-alpha and in turn promoted nuclear factor kappa-B and overrode the endogenous defence mechanisms. Conversely, pre-treatment of the hydrogen peroxide-exposed cells to melatonin or alpha-lipoic acid increased endogenous antioxidant enzymes, including superoxide dismutase-2 and heme oxygenase-1; moreover, they ameliorated significantly oxidative stress damage and partially reduced alterations in the muscle cells, which are typical of aging. In conclusion, melatonin was equally effective as alpha-lipoic acid; it exhibited marked antioxidant and anti-aging effects at the level of skeletal muscle in vitro even when it was given in a much lower dose than alpha-lipoic acid

Optimal Aging and Death: Understanding the Preston Curve

The present study examines whether the Preston curve reflects a causal impact of income on longevity or, for example, factors correlated with both income and life expectancy. In order to understand the Preston curve better, we develop a model of optimal intertemporal consumption in which the representative consumer is subject to physiological aging. In modeling aging we draw on recent research in the fields of biology and medicine. The speed of the aging process, and thus the time of death, are endogenously determined by optimal health investments. We calibrate the model to US data and proceed to show that the model accounts for nearly 80% of the cross-country differences in life expectancy that the Preston curve captures.aging; longevity; health investments; savings; Preston curve

Opportunities for organoids as new models of aging.

The biology of aging is challenging to study, particularly in humans. As a result, model organisms are used to approximate the physiological context of aging in humans. However, the best model organisms remain expensive and time-consuming to use. More importantly, they may not reflect directly on the process of aging in people. Human cell culture provides an alternative, but many functional signs of aging occur at the level of tissues rather than cells and are therefore not readily apparent in traditional cell culture models. Organoids have the potential to effectively balance between the strengths and weaknesses of traditional models of aging. They have sufficient complexity to capture relevant signs of aging at the molecular, cellular, and tissue levels, while presenting an experimentally tractable alternative to animal studies. Organoid systems have been developed to model many human tissues and diseases. Here we provide a perspective on the potential for organoids to serve as models for aging and describe how current organoid techniques could be applied to aging research