Proteomic Analysis of Blood Samples Points to the Importance of Inflammation in Aging
Chronic inflammation is a feature of aging, the constant inappropriate overactivation of the immune system. Many of the mechanisms that contribute to this unfortunate state are catalogued and understood to at least some degree, such as growing numbers of senescent cells, excess visceral fat tissue, numerous forms of molecular damage and debris that are interpreted as cues for immune activation, and so forth. While short-term inflammation is necessary to maintain tissue, respond to pathogens, and heal injuries, when unresolved that same signaling and changed cell behavior is very disruptive of tissue maintenance and function. Greater inflammation leads to worse outcomes over time, a more rapid onset and progression of all of the common age-related conditions. Suppression of chronic inflammation, preferably by cleaning up the damage that causes the immune system to respond in this way, is an important goal in the treatment of aging as a medical condition.
The biological bases of longevity are not well understood, and there are limited biomarkers for the prediction of long life. We used a high-throughput, discovery-based proteomics approach to identify serum peptides and proteins that were associated with the attainment of longevity in a longitudinal study of community-dwelling men age ≥65 years. Baseline serum in 1196 men were analyzed using liquid chromatography - ion mobility - mass spectrometry, and lifespan was determined during ~12 years of follow-up. Men who achieved longevity (≥90% expected survival) were compared to those who died earlier.
Rigorous statistical methods that controlled for false positivity were utilized to identify 25 proteins that were associated with longevity. All these proteins were in lower abundance in long-lived men and included a variety involved in inflammation or complement activation. Lower levels of longevity-associated proteins were also associated with better health status, but as time to death shortened, levels of these proteins increased. Pathway analyses implicated a number of compounds as important upstream regulators of the proteins and implicated shared networks that underlie the observed associations with longevity.
Overall, these results suggest that complex pathways, prominently including inflammation, are linked to the likelihood of attaining longevity. This work may serve to identify novel biomarkers for longevity and to understand the biology underlying lifespan.
Inflammation reduction might be one of the main reasons rapamycin can extend healthy live.
Does anybody know if there are human studies or self-experimentation combining rapamycin and senolytics ?
Why combine rapamycin and senolytics ?
Just tinker with your SIRT2.
An Acetylation Switch of the NLRP3 Inflammasome Regulates Aging-Associated Chronic Inflammation and Insulin Resistance
https://www.sciencedirect.com/science/article/abs/pii/S1550413120300097?via%3Dihub
It is well documented that the rate of aging can be slowed, but it remains unclear to which extent aging-associated conditions can be reversed. How the interface of immunity and metabolism impinges upon the diabetes pandemic is largely unknown. Here, we show that NLRP3, a pattern recognition receptor, is modified by acetylation in macrophages and is deacetylated by SIRT2, an NAD+-dependent deacetylase and a metabolic sensor. We have developed a cell-based system that models aging-associated inflammation, a defined co-culture system that simulates the effects of inflammatory milieu on insulin resistance in metabolic tissues during aging, and aging mouse models; and demonstrate that SIRT2 and NLRP3 deacetylation prevent, and can be targeted to reverse, aging-associated inflammation and insulin resistance. These results establish the dysregulation of the acetylation switch of the NLRP3 inflammasome as an origin of aging-associated chronic inflammation and highlight the reversibility of aging-associated chronic inflammation and insulin resistance.