Tag Archives: senescence

Not all species deteriorate with age, challenging study shows

For most creatures, mortality increases sharply with age – and we typically consider this to be natural. However, other animals, such as the hermit crab, the red abalone and the hydra, a microscopic freshwater animal experience very different trends enjoying almost constant levels of fertility and mortality. For the desert tortoise, the mortality even decreases as it gets older.

The desert tortoise. Source: BARBARA CARROLL/GETTY

A study published in Nature compared demographic patterns across 46 species, showing that it’s not always necessary for ageing to lead to senescence deterioration of mortality and fertility, with age. Owen Jones, a biologist at the University of Southern Denmark in Odense, who led the study explains:

“By taking a grand view and doing a survey across species, we found plenty of violations of this underpinning theory,” says Jones.

Comparing the fertility and mortality among 46 species is no easy task. They used published life-history data sets for 11 mammals, 12 other vertebrates, 10 invertebrates, 12 vascular plants and a green algae. The first interesting results started popping up pretty quickly: they found no correlation between the length of life and the degree of senescence.

web-t_0006 copyWhen they organized the species along a senescence continuum, mammals were clustered at one end of the spectrum, among the organisms that have an abrupt shift in mortality, and plants gathered at the other end, while birds and invertebrates were scattered throughout. Strictly biologically speaking, this appears to be very weird.

“The [evolutionary] theories we have are applicable in lots of situations — but they can’t explain some cases,” says Jones. “It’s not about throwing out old theories; it’s about modifying theories to work on all species.”

Ah, but is such an approach truly valid? Some scientists have spoken against the relevance of this kind of study.

“This approach is like making a fruit salad and imagining it can tell you something about evolution of the orange,” says Steven Austad, an evolutionary biologist at the University of Texas Health Science Center in San Antonio. “This comparison of demographic trajectories across the tree of life is completely divorced from biology and ignores the impact of the environment,” he adds.

Laurence Mueller, an evolutionary biologist at the University of California at Irvine also agrees that this approach is flawed:

“Organisms in the field die from a lot of causes — for example, predation or disease — other than ageing,” he says. “Unfortunately, the unknown source of mortality in field-data sets confounds the age-related patterns of senescence, which is what we’re all interested in,” he adds.

Still, study co-author Hal Caswell, a mathematical ecologist at Woods Hole Oceanographic Institution in Massachusetts, stands by his methods, explaining that the attempt of distinguishing whether or not senescence and mortality are related is a mistake:

“An increase in mortality with age represents a decline in the ability to deal with hazards of death, regardless of their source, and is defined as senescence,” he says.

Either way, this certainly shows that we still have a long way to go before we understand the full implications and mechanisms around senescence, and how they differ throughout species.

Hydra

Longevity gene that makes the Hydra immortal identified

HydraThe Hydra is a tiny animal that can be found in just about any freshwater pond, just a few millimeters long, that has attracted the attention of scientists for years now due to its extraordinary regenerative abilities. The Hydra is consider to be biological immortal – it does not die from old age – although a scientific consensus has yet to be reached. Scientists studying the polyp Hydra claim they now know how the creature escapes senescence after they found a key gene. This gene is also believed to be linked with aging in humans.

The animal’s potential immortality is made possible by its reproductive system. The Hydra is an asexual being and doesn’t mate, instead it reproduces by producing buds in the body wall, which grow to be miniature adults and simply break away when they are mature. Popular scientific consensus has found that animals that reproduce later on and less frequently tend to live longer. The Hydra, however, begins to reproduce almost immediately.

The forever young Hydra

Biology Professor Daniel Martínez at first was extremely skeptical of the claim that Hydras were biological immortal. He set out to disprove this assumptions and cultured tens of specimens, which he kept in isolation waiting for them to die. It’s already been four years and no specimen has yet succumbed from natural causes. For an animal of this size, nature dictates that it should have died long before.

Returning to the Hydra’s reproductive system. For this vegetative-only reproduction to work,  each polyp contains stem cells capable of continuous proliferation. “Hydra is a bag of stem cells,” Martinez says. “It is an adult that is produced by embryonic cells, so it is really a perennial embryo. The genes that regulate development are constantly on, so they are constantly rejuvenating the body.”

The gene that makes it all happen

As humans age, as well as many other complex biological lifeforms, stem cells lose the ability to proliferate and thus to form new cells. This causes tissue decline, which is why muscles get weakened with old age for instance. Influencing the processes that go with aging has been a goal for scientists science the advent of modern science. The Hydra might potentially have the ability to open new doors, especially after the latest research from scientists at the University Medical Center Schleswig-Holstein (UKSH) who recently found the gene that causes Hydra to be immortal – the FoxO gene.

Now, the gene itself isn’t something new. It’s been known by scientists for years and is present in all animals, and humans as well. However, until now it was not known why human stem cells become fewer and inactive with increasing age, which biochemical mechanisms are involved and if FoxO played a role in aging.

The German researchers genetically modified a batch of polyps such that they obtained Hydras with: no FoxO gene, deactivated FoxO gene and enhanced FoxO gene. Their  findings show that the animals with no FoxO gene have significantly fewer stem cells. Interestingly, the immune system in animals with inactive FoxO also changes drastically.

“Drastic changes of the immune system similar to those observed in Hydra are also known from elderly humans,” explains Philip Rosenstiel of the Institute of Clinical Molecular Biology at UKSH, whose research group contributed to the study.

The researchers go on to note that there’s a link between FoxO and aging in humans.

“Our research group demonstrated for the first time that there is a direct link between the FoxO gene and aging,” says Thomas Bosch from the Zoological Institute of Kiel University, who led the Hydra study. Bosch continues: “FoxO has been found to be particularly active in centenarians — people older than one hundred years — which is why we believe that FoxO plays a key role in aging — not only in Hydra but also in humans.”

Fighting aging in humans

That’s to say that FoxO has been proven to be linked with aging in humans, since testing such a hypothesis would require genetic modification of actual people. Remember, that the Hydra is an extremely primitive organism – immortal as it may be. Imagine that if you  take a hundred hydra, make a cell suspension, dissociate all the tissue, put it in a centrifuge, make it into a bowl, you’ll soon see how from those cells, somehow they bind together and you’ll get a couple of new hydras!

It’s been tested with mice, however, and apparently though they didn’t make them immortal, the enhanced gene therapy did in fact prolonged their lives considerably.

Here’s the take away: FoxO gene plays a decisive role in the maintenance of stem cells, according to these findings. I may be overstating this, so someone please correct me if so, but it also means that the FoxO gene determines life span in all animals, from simple being to the top of the food chain humans. So what’s the key to longevity? The maintenance of stem cells and the maintenance of a functioning immune system. If you you’ve got these two in cue, you’ve got nothing to worry about – except freak accidents!

I recommend you also read one of my earlier pieces which also discusses another immortal animal – that’s right, you’re own backyard flatworm. This little puppy can regenerate its cells indefinitely thanks to the telomerase enzyme, which keeps DNA telomeres from shrinking and thus also keeps cell regeneration indefinite.

The findings of the German scientists were documented in the journal Proceedings of the National Academy of Sciences(PNAS).

Intracellular controlled release of molecules within senescent cells was achieved using mesoporous silica nanoparticles (MSNs) capped with a galacto-oligosaccharide (GOS) to contain the cargo molecules (magenta spheres; see scheme). The GOS is a substrate of the senescent biomarker, senescence-associated β-galactosidase (SA-β-gal), and releases the cargo upon entry into SA-β-gal expressing cells.

Intelligent nanoparticles drop anti-aging cargo

A group of researchers have successfully tested a novel nanodevice treatment, in which intelligent nanoparticles selectively open and release drugs which target aging cells. The approach could render results when treating patients suffering from diseases involving tissue or cellular degeneration such as cancer, Alzheimer’s, Parkinson’s, accelerated aging disorders (progeria). It could also boosts results in the cosmetic industry, where anti-aging products are always welcomed.

Intracellular controlled release of molecules within senescent cells was achieved using mesoporous silica nanoparticles (MSNs) capped with a galacto-oligosaccharide (GOS) to contain the cargo molecules (magenta spheres; see scheme). The GOS is a substrate of the senescent biomarker, senescence-associated β-galactosidase (SA-β-gal), and releases the cargo upon entry into SA-β-gal expressing cells.

Intracellular controlled release of molecules within senescent cells was achieved using mesoporous silica nanoparticles (MSNs) capped with a galacto-oligosaccharide (GOS) to contain the cargo molecules (magenta spheres; see scheme). The GOS is a substrate of the senescent biomarker, senescence-associated β-galactosidase (SA-β-gal), and releases the cargo upon entry into SA-β-gal expressing cells.

Senescence is a physiological process of the body to eliminate aged cells or ones with alterations that may compromise their viability. In young, healthy bodies the senescence mechanisms prevents the accumulation of aged cells (senescent) in organs and tissues, which disrupts their proper functions, and sometimes lead to the apparition of tumors. As we continue to age, though, senescent accumulation is inevitable and age related diseases surface. The elimination of these cells would slow down the appearance of diseases associated with aging.

“The nanodevice that we have developed consists of mesoporous nanoparticles with a galactooligosaccharide outer surface that prevents the release of the load and that only selectively opens in degenerative phase cells or senescent cells. The proof of concept demonstrates for the first time that selected chemicals can be released in these cells and not in others,” says Ramón Martínez Máñez, researcher at the IDN Centre — Universitat Politècnica de València and CIBER-BBN member.

The scientists tested the new nanodevice in cell cultures derived of patients with accelerated aging syndrome dyskeratosis congenita. These cell cultures are characterized by a high concentration of senescent cells, due to high levels of beta-galactosidase activity – an enzyme which is associated with senescence. The researchers designed nanoparticles that open when the enzyme is detected release their contents in order to eliminate senescent cells, prevent deterioration or even reactivate for their rejuvenation.

“There are a number of diseases associated with premature aging of tissues, many of which affect very young patients and for whom there is no therapeutic alternative, as in the case of DC or aplastic anemia. Other diseases affect adults, as idiopathic pulmonary fibrosis or liver cirrhosis. These nanoparticles represent a unique opportunity to selectively deliver therapeutic compounds to affected tissues and rescue their viability and functionality” explains Rosario Perona, researcher at the Instituto de Investigaciones Biomédicas (CSIC/UAM) and CIBERER member.

The next step of this research is to test the devise with therapeutic agents and validate it in animal models.

“As far as we know this is the first time that a nanotherapy for senescent cells has been described. Although there is still far to go from these results to the possible elimination of senescent cells or rejuvenation therapies, we believe that our research may open new paths for developing therapies for the treatment of age-related diseases,” says Ramón Martínez Máñez.

Findings were published in the journal Angewandte Chemie International.