A fair-sized fraction of present aging research relates to epigenetic changes that occur with aging. Epigenetics is the study of gene expression, the process by which proteins are produced from genetic blueprints, and the many different ways in which gene expression changes in response to health and environmental factors. The machineries of life are controlled by dynamic alterations in circulating levels of specific proteins, and these ongoing changes in metabolism feed back into one another to produce a responsive, self-regulating system of enormous complexity.
The cellular and molecular damage of aging causes characteristic changes in gene expression, and these can be picked out from the more general set of random - or perhaps just less well-understood - changes in gene expression that occur over time. Researchers are primarily cataloging these changes, but some are also using increasingly efficient tools to restore the gene expression of specific genes to youthful levels in animal studies. To my eyes this will be the basis for therapies to treat age-related conditions that will prove to be more effective than the present state of the art. Nonetheless, it isn't the direct road to rejuvenation, as changing gene expression that is altered in response to damage doesn't deal with the underlying issue, which is the existence of that damage.
(As has been pointed out in comments on past posts, there isn't a clear line to be drawn between manipulating protein levels in a way that is less helpful versus doing so in a way that actually does address underlying damage. If you can alter levels of a protein so as to spur greater clearance of undesired misfolded protein aggregates, for example, then you are in fact creating some degree of rejuvenation. You are removing damage. But if, as is usually the case, changing gene expression to restore youthful operation of a system does nothing to repair underlying damage to that system, then it cannot be the best path forward. Consider, for example, restoring stem cell activity through changed gene expression: this most likely comes with a raised risk of cancer, as stem cell decline with aging is most likely an evolved response to increasing levels of damage in stem cells. Turn off that response and cancer rates should increase, even through great benefits to health through increased tissue maintenance can be realized).
A handful of recently published research results are illustrative of the sort of work being done at the intersection of epigenetics and aging.
[Researchers] tested the effect of daily, 30-minute baths in [dilute] bleach solution on laboratory mice with radiation dermatitis. They found that the animals bathed in the bleach solution experienced less severe skin damage and better healing and hair regrowth than animals bathed in water. They then turned their attention to old - but healthy - laboratory mice.
"Multiple research studies have linked increased NF-kB activity with aging. We found that if we blocked NF-kB activity in elderly laboratory mice by bathing them in the bleach solution, the animals' skin began to look younger. It went from old and fragile to thicker, with increased cell proliferation." The effect diminished soon after the dilute-bleach baths were stopped, indicating that regular exposure is necessary to maintain skin thickness. "We found that the bleach solution oxidizes and inhibits an activator necessary for NF-kB to enter the nucleus, essentially blocking NF-kB's effect."
The results came from the first genome-wide DNA methylation study in disease-free individuals. DNA methylation involves the addition of a methyl group to the DNA and is involved in a particular layer of epigenetic regulation and genome maintenance. In this study researchers compared DNA methylation in samples of skeletal muscle taken from healthy young (18 - 27 years of age) and older (68 - 89 years of age) males. [Researchers] looked at more than 480,000 sites throughout the genome. "We identified a suite of epigenetic markers that completely separated the younger from the older individuals - there was a change in the epigenetic fingerprint."
Scientists identified about six-thousand sites throughout the genome that were differentially methylated with age and that some of those sites are associated with genes that regulate activity at the neuromuscular junction which connects the nervous system to our muscles.
In yeast at least, the aging process appears to reduce an organism's ability to silence certain genes that need to be silenced. Now [researchers] who study the biology of aging have shown that the loss of genetic control occurs in fruit flies as well. In several newly published experiments they show that gene silencing via chromatin in fruit flies declines with age.
They also showed that administering life span extending measures to the flies, such as switching them to a lower calorie diet or increasing expression of the protein Sir2, restores the observed loss of gene silencing due to age.
The aging process causes an increase in percent body fat, but the mechanism remains unclear. In the present study we examined the impact of aging on brown adipose tissue (BAT) thermogenic activity as potential cause for the increase in adiposity. We show that aging is associated with iBAT morphological abnormalities and thermogenic dysfunction. In-vitro experiments revealed that brown adipocyte differentiation is defective in aged mice. Interscapular brown tissue in aged mice is progressively populated by adipocytes bearing white morphological characteristics. Aged mice fail to mobilize intracellular fuel reserves from brown adipocytes and exhibit deficiency in homeothermy.
Our results suggest a role for orexin-signaling in the regulation of thermogenesis during aging. Brown fat dysfunction and age-related assimilation of fat mass was accelerated in mice in which orexin-producing neurons were ablated. Conversely, orexin injections in old mice increased multilocular morphology, increased core body temperature, improved cold tolerance, and reduced adiposity. These results argue that BAT can be targeted for interventions to reverse age-associated increase in fat mass.