One of the interesting minor themes to arise from the modern study of the biochemistry of aging is that aging is accompanied by numerous subtle, detrimental changes in the processing of dietary amino acids, both essential amino acids that cannot be constructed by human cellular biology, and the others that can, but which are also obtained from the diet. Here I'll point out recent research into an age-related decline in a process that consumes the amino acid cysteine, but there have been others over the years.
One such decline discovered some years back is that a growing failure to process the essential amino acid leucine is perhaps linked to loss of muscle mass with age, a condition known as sarcopenia, possibly via a chain of issues that upsets the balance between mechanisms breaking down muscle proteins and mechanisms assembling them. This can be overcome to at least some degree by throwing more leucine at the problem: there is evidence for leucine supplementation in older adults to have some impact on outcomes. There are numerous publications on this topic from the past decade or more, but the full details of what it actually going on and why - and especially the nature of the root causes - remain to be firmly pinned down, and the evidence itself is not undisputed. That is the story at present for most of these fine details in the corner of the bigger picture.
This is especially interesting for those of us who practice some form of calorie restriction or protein restriction with the aim of methionine restriction. Low levels of the essential amino acid methionine seems to be the key trigger for much of the beneficial metabolic alteration that occurs in response to calorie restriction. Studies in mice show that life-long restriction in fact blunts sarcopenia. Yet here is another set of evidence to suggest that more of at least some constituents of protein has much the same effect. It is a reminder that outcomes in health and aging are many up of many strands.
The paper linked below presents a fairly similar situation to that of leucine and sarcopenia, but for cysteine and the production of cellular antioxidants necessary for the proper function of metabolism. Again there is some ability to overcome the issue by delivering more cysteine in the diet, perhaps a theme that might be repeated elsewhere in our biochemistry as well:
Restricted dietary intakes of protein or essential amino acids tend to slow aging and boost lifespan in rodents, presumably because they downregulate IGF-I/Akt/mTORC1 signaling that acts as a pacesetter for aging and promotes cancer induction. A recent analysis of the National Health and Nutrition Examination Survey (NHANES) III cohort has revealed that relatively low protein intakes in mid-life (under 10 % of calories) are indeed associated with decreased subsequent risk for mortality. However, in those over 65 at baseline, such low protein intakes were associated with increased risk for mortality. This finding accords well with other epidemiology correlating relatively high protein intakes with lower risk for loss of lean mass and bone density in the elderly. Increased efficiency of protein translation reflecting increased leucine intake and consequent greater mTORC1 activity may play a role in this effect; however, at present there is little solid evidence that leucine supplementation provides important long-term benefits to the elderly.
Aside from its potential pro-anabolic impact, higher dietary protein intakes may protect the elderly in another way-by providing increased amino acid substrate for synthesis of key protective factors. There is growing evidence, in both rodents and humans, that glutathione synthesis declines with increasing age, likely reflecting diminished function of Nrf2-dependent inductive mechanisms that boost expression of glutamate cysteine ligase (GCL), rate-limiting for glutathione synthesis. Intracellular glutathione blunts the negative impact of reactive oxygen species (ROS) on cell health and functions both by acting as an oxidant scavenger and by opposing the pro-inflammatory influence of hydrogen peroxide on cell signaling.
Fortunately, since GCL's K m for cysteine is close to intracellular cysteine levels, increased intakes of cysteine - achieved from whole proteins or via supplementation with N-acetylcysteine (NAC) - can achieve a compensatory increase in glutathione synthesis, such that more youthful tissue levels of this compound can be restored. Supplementation with phase 2 inducers - such as lipoic acid - can likewise increase glutathione levels by promoting increased GCL expression. In aging humans and/or rodents, NAC supplementation has exerted favorable effects on vascular health, muscle strength, bone density, cell-mediated immunity, markers of systemic inflammation, preservation of cognitive function, progression of neurodegeneration, and the clinical course of influenza - effects which could be expected to lessen mortality and stave off frailty.
Hence, greater cysteine availability may explain much of the favorable impact of higher protein intakes on mortality and frailty risk in the elderly, and joint supplementation with NAC and lipoic acid could be notably protective in the elderly, particularly in those who follow plant-based diets relatively low in protein. It is less clear whether the lower arginine intake associated with low-protein diets has an adverse impact on vascular health.
While interesting as a theme, all of this is still small potatoes in the grand scheme of things: a great deal of data boils down to small effects on long-term health. You cannot use diets and supplements to greatly alter the tiny odds of passing beyond 100 years of age in the environment of today's medical technology. This is true for much of the study of aging, with its primary focus on mapping the entirety of cellular metabolism and its changes over time, rather than on the production of far more effective treatments. A different approach to the problem is required for meaningful progress towards greater healthy longevity, a focus on repair of the known root causes of aging, on the actual treatment of aging rather than continued investigation of the fine details of how aging progresses when left untreated, or how to tinker a little more function out of a damaged biochemistry. Repair is the way forward, aiming to reverse the damage, as exemplified by the SENS rejuvenation research programs.