I strongly encourage everyone interested in healthy life extension to put in at least a little time to become familiar with the underlying science and concepts - how else are you to distinguish the cranks from the forward-looking researchers and advocates, if not by educating yourself as a layman? It also pays to garner a better understanding of the way in which the scientific method - the foundation of science - works in practice; you'll be far better equipped to identify the strength of support for of a concept, as well as those trying to game the system by cherry-picking results. On this latter topic, you might want to read a couple of related posts from back in the archives:

After you have the basics down, it can't hurt to regularly stroll through the searchable archives at PubMed, or similar resource for scientific publications. It's easy enough to skip over the densely worded material that is presently beyond you (and there will always be material that is beyond you - science has grown to the point at which very technical discussions in any given field are beyond casual reading even for other scientists), and you'll usually find something interesting and new. Don't be intimidated by new words, long words and unfamiliar names; that's what Google and Wikipedia are for - make use of these resources, and benefit by them. You'll find that a good deal of scientific nomenclature is simply a matter of precision in naming, and mostly easy and helpful once you get into the swing of things. The process of learning about present research - the sort of thing you won't find in a textbook - is one of identifying common threads, and finding the links that transform what you read into a coherent whole.

Running a quick search in PubMed for "aging" today, and ordering by date, I fished out up the following items of interest from recent publications:

Decreased neurogenesis in aged rats results from loss of granule cell precursors without lengthening of the cell cycle

It is well established that neurogenesis in the dentate gyrus slows with aging, but it is unclear whether this change is due to slowing of the cell cycle, as occurs during development, or to loss of precursor cells. ... Taken together, these findings indicate that precursor cells [are] lost from throughout the dentate gyrus in old age with no concomitant change in the cell cycle time.

This first paper is interesting because it contributes to an ongoing debate I have had my eye on for some months: researchers know that stem cell activity and accompanying regenerative capabilities diminish with age. The logical explanation is that this is an evolutionary adaptation to reduce the risk of cancer due to the activity of age-damaged cells. But is there less activity due to a decline in the number of stem cells, or because the stem cells are performing less work due to environmental cues or changes in regulatory mechanisms? The strategies for restoring function - assuming you have a way to deal with the cancer risk to hand - would be different in either case, and the papers demonstrating evidence for both sides of the debate are piling up.

Molecular signaling and genetic pathways of senescence: Its role in tumorigenesis and aging

In response to progressive telomere shortening in successive cell divisions, normal somatic cells enter senescence, during which they cease to proliferate irreversibly and undergo dramatic changes in gene expression. Senescence can also be activated by various types of stressful stimuli, including aberrant oncogenic signaling, oxidative stress, and DNA damage. Because of the limited proliferative capacity imposed by senescence, as well as the ability of senescent cells to influence neighboring non-senescent cells, senescence has been proposed to play an important role in tumorigenesis and to contribute to aging.

WRN at telomeres: implications for aging and cancer

Werner Syndrome (WS) is a premature aging syndrome characterized by early onset of age-related pathologies and cancer. Since WS is due to a single gene defect, it has attracted much interest from researchers seeking to understand pathways that contribute to cancer and aging at cellular and molecular levels. The protein mutated in WS, WRN, appears to play a major role in genome stability, particularly during DNA replication and telomere metabolism. Much of the pathophysiology associated with WS, including the rapid onset of cellular senescence, early cancer onset and premature aging, can be attributed to a defect in telomere maintenance.

Telomeres - the protective ends of chromosomes that are worn away with progressive cell division - and cellular senescence play an important part in the developing picture of aging. Telomeres, and the various biochemical mechanisms for shortening and lengthening them, are the lynchpin connecting aging and cancer, part of an evolutionary balance between too little cellular regeneration and too great a risk of developing cancer. Werner syndrome is one window allowing scientists to learn more about this system as a whole - and how to manipulate it. A number of research groups are presently working on the control of telomeres with the goal of treating age-related disease or intervening in aging - it remains to be seen just where this path will go.

Microglia derived from aging mice exhibit an altered inflammatory profile

Microglia play a critical role in neurodegenerative diseases and in the brain aging process. Yet, little is known about the functional dynamics of microglia during aging. ... Aging microglia were characterized by the presence of lipofuscin granules, decreased processes complexity, altered granularity, and increased mRNA expression of both pro-inflammatory (TNFalpha, IL-1beta, IL-6) and anti-inflammatory (IL-10, TGFbeta1) cytokines. ... The low but sustained production of pro-inflammatory cytokines by aging microglia may have a profound impact in the brain aging process.

Two items here: the first is the presence of lipofuscin, one of the many "junk" chemicals that build up in the body with aging; lipofuscin is demonstrated to damage a number of important processes in the day to day operation of cells. Lipofuscin is a target for some research groups, including the LysoSENS bioremediation research funded by Methuselah Foundation donors. If you could remove this buildup of junk from cells, a number of processes would improve - this would in fact be the repair of some facets of aging in the treated tissues.

The second item is inflammation: we know that chronic inflammation over years and decades is a cause of accumulating damage in the body. This is why too much fat is a bad thing - it pumps out the cytokines too. You might find some of the information online on "inflammaging" interesting; the puzzle of the aging immune response is that it does too little and too much at the same time. It runs rampant with damaging inflammatory signaling, and yet accomplishes little of its job.

These last two papers relate to another topic of interest that I have been watching in recent months: the effect of antioxidants in cellular mitochondria on healthy life span. Antioxidants applied liberally to our biochemistry (such as those taken as supplements) appear to have little or no benefit. More advanced methologies of localizing antioxidants to the mitochondria have been shown to increase life span in mice by 20-30% or so - but this is a good deal more of an engineering proposition than a matter of ingesting the right chemicals.

Age-related changes in mitochondrial function and antioxidative enzyme activity in fischer 344 rats

The disintegration of mitochondrial membrane integrity was determined higher in the liver of old rats than that of young rats. This was well correlated with the decrease of total superoxide dismutase (SOD), Cu/Zn-SOD, Mn-SOD and glutathione peroxidase activities in most of the organs, except for the increase of catalase activity in heart of old rats. Similarly, the protein expressions of these enzymes were down regulated in the liver and kidney of old rats. Taken together, we suggest that the mitochondrial malfunction in old rats is associated with the decrease of antioxidative enzyme efficiency.

Hippocampal long-term potentiation, memory, and longevity in mice that overexpress mitochondrial superoxide dismutase

Mitochondrial superoxide dismutase (SOD-2 or Mn-SOD) is a key antioxidant enzyme that scavenges superoxide. Thus, SOD-2 may not only prevent aging-related oxidative stress, but may also regulate redox signaling in young animals. We used transgenic mice overexpressing SOD-2 to study the role of mitochondrial superoxide in aging, synaptic plasticity, and memory-associated behavior. We found that overexpression of SOD-2 had no obvious effect on synaptic plasticity and memory formation in young mice, and could not rescue the age-related impairments in either synaptic plasticity or memory in old mice. However, SOD-2 overexpression did decrease mitochondrial superoxide in hippocampal neurons, and extended the lifespan of the mice. These findings increase our knowledge of the role of mitochondrial superoxide in physiological and pathological processes in the brain.

Why the benefit from more antioxidants in the mitochondria? Well, mitochondria are damaged by free radicals such as superoxide, and this leads to a range of age-related damage and resulting degeneration throughout the body via an interesting process of many steps. But the normal operations of mitochondria (energy generation for the cell) are the source of the vast majority of these damaging free radicals - in other words, if you want to reduce the damage to mitochondria by soaking up those free radicals, you'd better put the antioxidants right at the source. Anywhere else just won't do the job.

I hope that this provides something of an illustration of the way in which you can look into aging research yourself, and learn something of what the research community is presently working on. Knowledge is power.

Technorati tags: aging, medical research, science