Interventions to Slow Aging in Humans: Are We Ready?

Abstract

The workshop entitled ‘Interventions to Slow Aging in Humans: Are We Ready?’ was held in Erice, Italy, on October 8–13, 2013, to bring together leading experts in the biology and genetics of aging and obtain a consensus related to the discovery and development of safe interventions to slow aging and increase healthy lifespan in humans. There was consensus that there is sufficient evidence that aging interventions will delay and prevent disease onset for many chronic conditions of adult and old age. Essential pathways have been identified, and behavioral, dietary, and pharmacologic approaches have emerged. Although many gene targets and drugs were discussed and there was not complete consensus about all interventions, the participants selected a subset of the most promising strategies that could be tested in humans for their effects on healthspan. These were: (i) dietary interventions mimicking chronic dietary restriction (periodic fasting mimicking diets, protein restriction, etc.); (ii) drugs that inhibit the growth hormone/IGF-I axis; (iii) drugs that inhibit the mTOR–S6K pathway; or (iv) drugs that activate AMPK or specific sirtuins. These choices were based in part on consistent evidence for the pro-longevity effects and ability of these interventions to prevent or delay multiple age-related diseases and improve healthspan in simple model organisms and rodents and their potential to be safe and effective in extending human healthspan. The authors of this manuscript were speakers and discussants invited to the workshop. The following summary highlights the major points addressed and the conclusions of the meeting.

A salicylic acid derivative extends the lifespan of Caenorhabditis elegans by activating autophagy and the mitochondrial unfolded protein response

“…This may in part explain why they held promise as treatments to improve insulin resistance and type 2 diabetes. AMPK has also been suggested to control the aging process in general (Salminen & Kaarniranta, 2012), and targeting AMPK has been discussed as a potential strategy to slow down aging in humans (Longo et al, 2015). Interestingly, ASA has recently been revealed as a lifespan‐extending treatment in both mice and nematodes (Ayyadevara et al, 2013; Strong et al, 2008; Wan, Zheng, Wu, & Luo, 2013).…”

Role of dietary amino acid balance in diet restriction‐mediated lifespan extension, renoprotection, and muscle weakness in aged mice

“…Whether there is some specificity to the effects of restriction of different essential amino acids is still under debate (Longo et al., 2015). Therefore, the amino acid profiles of homogenates of kidney samples obtained from the four groups of aged mice were evaluated, to identify an amino acid that might be responsible for the adverse effects of EEA supplementation in the diet‐restricted aged mice.…”

Metformin alleviates human cellular aging by upregulating the endoplasmic reticulum glutathione peroxidase 7

“…Over the past decades, scientific studies on aging have demonstrated that genetic modulation can extend lifespan in diverse model organisms and have established that aging can be targeted by dietary and pharmacologic interventions (Longo et al., 2015). Metformin, the most widely used antidiabetic drug in the world, has been reported to favorably influence metabolic and cellular processes closely associated with the development of aging and even to delay aging in animal models (Novelle et al., 2016).…”