Fruit fly intestine may hold secret to the fountain of youth

The positive effect of calorie restriction on lifespan in many organisms is well established, but scientists are still working to understand the mechanism. The latest finding, in fruit flies, is that artificially increasing the number of mitochondria in the cells of the intestines – which happens naturally under conditions of calorie restriction – may be partially responsible for the effect.

Fruit fly intestine may hold secret to the fountain of youth

This chain of connections between the mitochondria and longevity inspired Jones and her colleague to investigate what happens when the PGC-1 gene is forced into overdrive. To do this, they used genetic engineering techniques to boost the activity of the fruit fly equivalent of the PGC-1 gene. The flies (known as Drosophila melanogaster) have a short lifespan, allowing the scientists to study aging and longevity in ways that aren’t as feasible in longer-lived organisms such as mice or human.

The researchers found that boosting the activity of dPGC-1, the fruit fly version of the gene, resulted in greater numbers of mitochondria and more energy-production in flies – the same phenomenon seen in organisms on calorie restricted diets. When the activity of the gene was accelerated in stem and progenitor cells of the intestine, which serve to replenish intestinal tissues, these cellular changes correspond with better health and longer lifespan. The flies lived between 20 and 50 percent longer, depending on the method and extent to which the activity of the gene was altered.

The research suggests that the mechanism by which health and longevity are increased involves greater robustness in the intestinal tissue as a result of having more mitochondria.

Modulation of Longevity and Tissue Homeostasis by the Drosophila PGC-1 Homolog

[W]e show that overexpression of the Drosophila PGC-1 homolog (dPGC-1/spargel) is sufficient to increase mitochondrial activity. Moreover, tissue-specific overexpression of dPGC-1 in stem and progenitor cells within the digestive tract extends life span. Long-lived flies overexpressing dPGC-1 display a delay in the onset of aging-related changes in the intestine, leading to improved tissue homeostasis in old flies. Together, these results demonstrate that dPGC-1 can slow aging both at the level of cellular changes in an individual tissue and also at the organismal level by extending life span. Our findings point to the possibility that alterations in PGC-1 activity in high-turnover tissues, such as the intestine, may be an important determinant of longevity in mammals.

Do Bacteria Age? Biologists Discover the Answer Follows Simple Economics

Do bacterial cells get “older” after repeated divisions? What would that even mean, once an original “mother” cell has divided into two “daughters”? Well, there are certain things one might look for as indicators of aging. For example, accumulation of molecular damage and slower rates of division in succeeding generations.

Previous studies have given conflicting results. One one hand it seems that many bacterial cells in later generations do show signs of having aged. But on the other, if aging is measured over the average of the whole population, it isn’t found.

The latest study found that, just as a population genetic model predicted would be optimal, half the daughter cells in a new generation appeared to be young and rejuventated, while the other half had accumulated the signs of aging.

Do Bacteria Age? Biologists Discover the Answer Follows Simple Economics

“Aging in organisms is often caused by the accumulation of non-genetic damage, such as proteins that become oxidized over time,” said Lin Chao, a professor of biology at UC San Diego who headed the study. “So for a single celled organism that has acquired damage that cannot be repaired, which of the two alternatives is better—to split the cellular damage in equal amounts between the two daughters or to give one daughter all of the damage and the other none?”

The UC San Diego biologists’ answer—that bacteria appear to give more of the cellular damage to one daughter, the one that has “aged,” and less to the other, which the biologists term “rejuvenation”—resulted from a computer analysis Chao and colleagues Camilla Rang and Annie Peng conducted on two experimental studies.

Further reading:

Temporal Dynamics of Bacterial Aging and Rejuvenation

Erasing the Signs of Aging in Human Cells Is Now a Reality

Human induced pluripotent stem cells (iPSCs) are adult body cells that have been treated in vitro to revert to a pluripotent state very close to embryonic stem cells. They were first produced in 2007, and the process of generating them has become progressively faster and more efficient. The resulting iPSCs now also have fewer defects and are less susceptible to becoming cancerous.

Although iPSCs are not precisely the same as embryonic stem cells, they share the property of lacking all traces of cellular aging, such as shortened telomeres and altered metabolism. In other words, they have been rejuvenated, having full-length telomeres and normal mitochondrial metabolism, gene expression profiles, and levels of oxidative stress.

Like other pluripotent cells, iPSCs can in principle differentiate into any type of body cell. Progress is being made in figuring out the exact recipe needed to actually produce cells that are equivalent to any adult cell type – some types are easier to make than others.

Given adult cells, of any particular type, derived from iPSCs, the natural question is whether such cells are also free of traces of aging that existed in the original adult cells from which the iPSCs were derived. The answer is that they are rejuvenated in comparison to the cells they were originally derived from – even if those original cells came from human centenarians, and (surprisingly) even if the original cells had entered the senescent stage in which they could no longer divide.

Of course, all this work was accomplished in vitro. There’s no obvious way to apply it to the whole body of an older person, or even to a complex organ. Perhaps such cells can eventually be used as a therapy for patients with Parkinson’s disease or to grow replacement arteries or tracheas. But that kind of development is still somewhere in the future.

Erasing the Signs of Aging in Human Cells Is Now a Reality

[S]enescent cells, programmed into functional iPSC cells, re-acquired the characteristics of embryonic pluripotent stem cells.

In particular, they recovered their capacity for self-renewal and their former differentiation potential, and do not preserve any traces of previous aging. To check the “rejuvenated” characteristics of these cells, the researchers tested the reverse process. The rejuvenated iPSC cells were again differentiated to adult cells and compared to the original old cells, as well as to those obtained using human embryonic pluripotetent stem cells (hESC).

“Signs of aging were erased and the iPSCs obtained can produce functional cells, of any type, with an increased proliferation capacity and longevity,” explains Jean-Marc Lemaitre who directs the Inserm AVENIR team.

The key to this new development was finding an improved recipe for the transcription factors used to effect reprogramming. In addition to the usual four factors (OCT4, SOX2, c-MYC and KLF4), the researchers included NANOG and LIN28 to erase traces of cell senescence.

Further reading:

Ageing stem cells from centenarian rejuvenated

‘Rejuvenated’ stemcells coaxed from centenarian

Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state