“The pathways that control cell processes and development work differently in older cells and are downregulated, meaning regeneration is impacted the older we get.
“If we can understand these pathways, however, we could potentially identify new therapies and interventions to mitigate the problem.”
an excerpt:
At the end of the regeneration, however, extracellular matrix-related processes were the most enriched in young cells (Figure [6(c)], whereas skeletal muscle processes (i.e., muscle adaptation, contraction, hypertrophy, and relaxation) remained overrepresented in aged cells (Figure [6(d)]. A closer analysis of GO enrichment demonstrates the downregulation of these biological processes in aged (Figure [6(f)]but not in young cells (Figure [6(e)], which could explain the impaired muscle cell regeneration in aged muscle shown in the morphological analysis.
My guess is that there is a lot of junk accumulated in the extracellular matrix in old organisms and we’d probably do better to make the highest priority keeping junk from accumulating rather than putting more junk in.
Old rats (20 months of age) were separated into two groups: a control group and a group (IBU) in which low grade inflammation had been reduced with a non-steroidal anti inflammatory drug (ibuprofen). After 5 months of treatment, inflammatory markers and cytokine levels were significantly improved in treated old rats when compared with the controls: -22.3% fibrinogen, -54.2% alpha2-macroglobulin, +12.6% albumin, -59.6% IL(6) and -45.9% IL(1beta) levels. As expected, food intake had no effect on muscle protein synthesis or muscle proteolysis in controls whereas it significantly increased muscle protein synthesis by 24.8% and significantly decreased proteolysis in IBU rats. The restoration of muscle protein anabolism at the postprandial state by controlling the development of low grade inflammation in old rats significantly decreased muscle mass loss between 20 and 25 months of age.
So… if it works in humans maybe a simple Advil treatment reduces sarcopenia and inflammaging.
Another reference is this study from the Buck Institute back in 2014 that has both Matt Kaeberlein and Brian Kennedy as coauthors:
The common non-steroidal anti-inflammatory drug ibuprofen has been associated with a reduced risk of some age-related pathologies. However, a general pro-longevity role for ibuprofen and its mechanistic basis remains unclear. Here we show that ibuprofen increased the lifespan of Saccharomyces cerevisiae , Caenorhabditis elegans and Drosophila melanogaster , indicative of conserved eukaryotic longevity effects. Studies in yeast indicate that ibuprofen destabilizes the Tat2p permease and inhibits tryptophan uptake. Loss of Tat2p increased replicative lifespan (RLS), but ibuprofen did not increase RLS when Tat2p was stabilized or in an already long-lived strain background impaired for aromatic amino acid uptake. Concomitant with lifespan extension, ibuprofen moderately reduced cell size at birth, leading to a delay in the G1 phase of the cell cycle. Similar changes in cell cycle progression were evident in a large dataset of replicatively long-lived yeast deletion strains. These results point to fundamental cell cycle signatures linked with longevity, implicate aromatic amino acid import in aging and identify a largely safe drug that extends lifespan across different kingdoms of life.
Results: We identified 49,349 cases and 196,850 controls. Compared with no NSAID use, the adjusted odds ratios for AD among NSAID users decreased from 0.98 for ≤1 year of use (95% CI 0.95–1.00) to 0.76 for >5 years of use (0.68–0.85). For users of ibuprofen, it decreased from 1.03 (1.00–1.06) to 0.56 (0.42–0.75). Effects of other NSAID classes and individual NSAIDs were inconsistent. There was no difference between a group of Aβ1-42-suppressing NSAIDs and others.
Wow! That 0.56 odds ratio for > 5 years for ibuprofen users is small.