All articles tagged with #somatic mutations
A lineage-tracing study shows that aging human brains replace resident microglia with circulating immune cells, revealing a surprising brain–body immune link; somatic mutations are used to map the microglial lineage across life.
Pando is a single clone of quaking aspens in Utah: about 47,000 trunks over 106 acres connected by one shared root system, weighing around 6,000 tonnes, making it possibly the heaviest living thing on Earth, with an age estimate of 16,000–80,000 years based on somatic mutations; the clonal organism keeps sprouting new stems as old ones die, but deer browsing and other factors threaten regeneration, prompting management efforts and raising questions about somatic mutation and longevity in long-lived organisms.
A Skolkovo Institute study in NPJ Aging uses a mathematical model to estimate a hard human lifespan limit if only DNA mutations remain as aging causes; average life is projected at about 146–194 years, with some potentially over 550. The cap would come from irreversible damage to the heart and brain, while other organs renew. The model is simplified and doesn’t account for organ interactions, but it offers a starting point toward a broader aging theory; experts note ageing could also be driven by cellular programming rather than wear and tear.
A new study uses accumulated somatic mutations to trace human microglial origins, revealing that marrow-derived cells infiltrate aging brains, resemble microglia, and can become a large fraction of the microglial pool; cohort data also show a protective association between clonal hematopoiesis and Alzheimer's disease, suggesting aging brains recruit marrow-derived myeloid cells into the microglial population.
A new NPJ Aging study uses a mathematical model to show that somatic mutations cap human lifespan around 146–194 years; without somatic mutations, the model would allow a median of about 1,759 years and a maximum near 29,921 years, but once mutations are included, immortality remains unlikely. The findings highlight neurons and heart cells as critical bottlenecks and suggest that realistic gains come from addressing these mutations or other aging hallmarks, while healthy lifestyle choices can still add healthy years.
A Skolkovo Institute study estimates that if somatic mutations were the only aging factor, the median human lifespan would cap at about 146–194 years, with liver and skin able to renew for millennia while heart and brain limits would keep the maximum around 208 years, indicating mutations contribute to aging but other mechanisms also constrain mortality.
A Russian-led modelling study estimates that if all reversible aging processes were reversed except for DNA damage in cells (somatic mutations), the median human lifespan could reach 146–194 years—a roughly twofold increase over today—while the ultimate cap would still hover around 200 years; the result hinges on how organs interact and on assumptions about aging hallmarks, making it a theoretical rather than experimental finding.
A July 2026 npj Aging paper proposes that removing the effects of somatic mutations could allow humans to live as long as 156 years, challenging the long-standing ~122-year limit. The model accounts for DNA damage but acknowledges other aging processes (mitochondrial dysfunction, epigenetic drift, telomere shortening, proteostasis loss). Experts say protecting DNA in non-regenerating organs like the brain and heart is crucial, while lifestyle measures—not smoking, healthy weight, good sleep, vaccines, and preventive care—can still meaningfully extend healthy years; there is no magic pill yet.
A computational study from the Skolkovo Institute suggests that, even if other aging processes were eliminated, random somatic DNA mutations could impose a hard ceiling on human lifespan around 146–194 years. The researchers built a mathematical model to quantify how mutation accumulation affects major organs, noting that tissues capable of continual cell replacement (like skin and liver) fare better than long‑lived cells in the heart and brain, which drive the limits. The work doesn’t predict future lifespans but provides a framework to measure the contribution of different aging processes and prioritize research toward a mechanistic theory of aging.
A July 2026 npj Aging paper from Russia suggests humans could live as long as 156 years if the effects of somatic mutations were removed, though other aging processes and non-regenerating brain and heart tissues still limit healthy years; meanwhile, lifestyle factors like not smoking, maintaining a healthy weight, vaccines, and cancer screenings can add about a decade to life expectancy, with the current oldest person at 116 illustrating present limits.
Analysis of ~736,000 UK Biobank and All of Us genomes shows that age-related mtDNA mutations in blood mainly arise from replication-errors that create low-level, cryptic heteroplasmy, which becomes detectable as people age due to clonal hematopoiesis (CH) expanding certain blood cell clones. The mutations are heavy-strand biased (C>T and A>G), occur at low heteroplasmy, and appear neutral with little evidence of positive selection. GWAS highlight CH-linked loci near TERT, TCL1A and SMC4, and rare-variant analyses implicate CH driver genes; Mendelian randomization indicates CH increases mtSNV burden, not vice versa. CH carriers have more age-accumulating mtSNVs and higher risk of hematologic cancers, suggesting mtSNV burden is a marker of somatic mosaicism. The study proposes a two-step model: random replication errors generate cryptic mtDNA variation, which becomes detectable when CH-driven clonal expansion reveals these variants with age.
Ultra-accurate sequencing shows somatic mutations in immune cells, especially B cells, can disable immune brakes and drive thyroid autoimmune diseases (Hashimoto’s and Graves’). This polyclonal evolution suggests a new mechanism beyond inheritance and hints at precision therapies that target mutant cell clones rather than broad immune suppression.
Using whole-exome sequencing and NanoSeq, researchers detected numerous B-cell clones with loss-of-function mutations in HVEM (TNFRSF14) and PD-L1 (CD274) in inflamed autoimmune thyroid tissue. In highly inflamed samples there are tens to hundreds of independent mutant clones, often with multiple hits and occasional biallelic loss, localizing to self-reactive B cells and supporting a model in which somatic immune-regulatory mutations contribute to thyroid autoimmunity.
A study investigates the impact of mitochondrial ancestry and tissue type on the somatic evolution of the mitochondrial genome through age using a panel of mouse strains with identical nuclear genomes but differing mitochondrial haplotypes. Duplex sequencing was used to profile mitochondrial genomes at an unprecedented level of depth and accuracy, revealing mutational hotspots and signatures of selection shaping the mitochondrial genome through age. The study identified haplotype- and tissue-specific mutational hotspots, replication errors, and deletions as dominant sources of mitochondrial somatic mutations, shedding light on the dynamics of mitochondrial evolution and its implications for ageing and age-related phenotypes.