There are now many lineages of genetically engineered mice that exhibit longer healthy, median, and maximum life spans, though none have yet come close to the 60-70% record set by growth hormone loss of function mutants. It is no longer newsworthy for a new variety of long-lived mouse to be discovered, and indeed many now pass by without comment. Extending life in mice by 10-30% through a single genetic alteration is a commonplace occurrence. Many of these interventions work through an overlapping set of related mechanisms that can be manipulated at many points, such as increased cellular housekeeping, and many are related to the calorie restriction response, the increase in health and life span that occurs due to a lower calorie intake.
Slowing aging by altering the operation of metabolism is ultimately not the real path to extending human life spans. Firstly where we can make direct comparisons between results in short-lived animals and results in humans, the effects on human life span are minimal even when the short term health benefits are similar. Calorie restriction certainly doesn't extend life by 40% in humans as it can in mice. Growth hormone loss of function mutations in humans such as Laron syndrome do not produce people who live vastly longer than the rest of us. Secondly a way slow aging will not help old people: what good is it to slow down the rate of damage accumulation for someone already so damaged as to be close to death? We want damage repair, means of rejuvenation, not mere slowing of the decline. Thirdly it is proving to be enormously expensive to make any real progress on this front: billions of dollars over two decades has produced only knowledge, and no practical treatment that comes anywhere near the proven benefits provided by regular moderate exercise or calorie restriction.
Slowing aging is a great way to investigate the vast unknown areas of cellular metabolism if the end goal is only knowledge, producing the catalog of human metabolism down to the tiniest detail, and not a matter of extending human life span. If we want longer lives, then the research community should be focused on rejuvenation through damage repair, which is a completely different research strategy in comparison to slowing aging. The aim is not to alter the operation of metabolism at all, but instead to periodically sweep away the damage that occurs as a side-effect of its normal operation.
This is not to say that research into slow-aging mutants is uninteresting. On the contrary, it is exciting stuff if you like to follow progress in the life sciences. A great deal is being learned and scarcely a day goes by without something newsworthy turning up. For example there is this open access paper, in which a calorie-restriction-like method of extending life is shown to improve wound healing in old age. Note that this lineage of long-lived mice (exhibiting a 20% increase in life span or thereabouts) was not created for that purpose, and has existed for more than 20 years. The canonical review paper on their longevity is from 1999. It is entirely possible that there are as yet a range of mouse lineages in labs that exhibit modest life extension and yet no-one has noticed because life span studies haven't been carried out:
Although there is no clear consensus on whether aging affects the quality of skin wound healing (SWH), the rate of SWH is often used as one of the biomarkers for biological age and could be indicative of a longevity phenotype. However, a clear-cut answer as to whether the longevity phenotype is associated with accelerated SWH remains obscure. Even in case of calorie restriction (CR), one of the most successful longevity-promoting interventions in mammals, the few studies conducted thus far did not bring about decisive results.
To address this issue, we investigated SWH in the long-lived transgenic αMUPA mice, a unique genetic model of extended lifespan. The αMUPA mice carry a transgene speciﬁcally expressed in the ocular lens. Being initially generated in 1987 to investigate eye pathologies, these transgenic mice were unexpectedly found to display a longevity phenotype. Compared to their wild type (WT) counterparts, the αMUPA mice spontaneously eat less when fed ad libitum, and live longer. The αMUPA mice also maintain an overall young look and physical activity at advanced ages and show a significantly reduced rate of spontaneous and induced tumorigenesis. Thus, the αMUPA mice share many common features with CR, yet are not hindered by several major drawbacks of CR such as hunger-induced stress and a need for individual housing (social stress). In view of using αMUPA mice as a CR-mimicking model to study the impact of CR on SWH, it is important to stress that the αMUPA mice strongly express the transgene in the ocular lens and ectopically in the brain but not in the skin, thus excluding the gene-specific effects on SWH.
We found that αMUPA mice showed a much slower age-related decline in the rate of WH than their wild-type counterparts. After full closure of the wound, gene expression in the skin of old αMUPA mice returned close to basal levels. In contrast, old wild-type mice still exhibited significant upregulation of genes associated with growth-promoting pathways, apoptosis and cell-cell/cell-extra cellular matrix interaction, indicating an ongoing tissue remodeling or an inability to properly shut down the repair process. It appears that the CR-like longevity phenotype is associated with more balanced and efficient WH mechanisms in old age, which could ensure a long-term survival advantage.