We Help People Dealing With Aging By Curating Relevant Information and News About Aging and Anti-Aging.

getting-older-news-logo

Unlocking the Fountain Of Youth

By Tom Seest

Can This Anti Aging Gene Protect Your Heart?

At GettingOlderNews, we help people who want to learn more about aging and anti-aging.

An anti-aging gene found commonly among centenarians may help protect their hearts from premature aging, potentially leading to novel therapeutic approaches for extending health span and warding off age-related diseases. The results of this research may provide avenues for developing therapeutic approaches aimed at prolonging health span and mitigating age-related ailments.
Ten years after Kyoto University biologist Shinya Yamanaka won a Nobel prize for developing a cocktail of proteins that transform adult skin cells into versatile stem cells, Harvard researchers believe they have discovered ways to turn back the clock on mice.

Can This Anti Aging Gene Protect Your Heart?

Can This Anti Aging Gene Protect Your Heart?

Is Bpifb4 the Key to Longevity?

The BPIFB4 gene produces a protein found in salivary glands, mononuclear cells, germline stem cells and progenitor cells. Studies have revealed it to possess anti-aging properties as it plays an essential role in multiple biological pathways associated with cell longevity; as well as promote regeneration and reduce oxidative stress levels. It may even act as a regulator of age-related gene expression patterns; its regulation prevents accumulation of mitochondrial oxidative damage as well as activating of the ERK/MAPK signaling pathway as well as delaying degradation of protein AMPK.
BPIFB4 gene variants associated with longevity have been linked to exceptionally long lifespans for humans and protection from heart disease in rodents, while studies in human cells indicate that BPIFB4 promotes new blood vessel formation while decreasing senescent cell accumulation, helping extend healthy vascular aging processes and prolong healthy lifespan. Discovering these genes could lead to treatments which extend biological age by reversing age-related changes.
BPIFB4 is a nuclear protein with a cytoplasmic domain, found in various tissues and cells including liver, skeletal muscle and kidneys. As part of the BPI/LBP/PLUNC family it plays an essential role in host defense responses against bacteria and pathogens; human populations have identified its gene, known as C20orf186/RY2G5.
Studies have demonstrated that mutations of the BPIFB4L gene, commonly referred to as BPIFB4L, are linked with extended human longevity across three independent cohorts. Its anti-ageing properties may include increasing endothelial NO release from endothelial cells and encouraging revascularization processes.
As another aspect, BPIFB4 protein variants, fragments, polynucleotides or vectors may be provided for use in the prevention, reduction of risk, amelioration or treatment of various pathologies including arterial hypertension, atherosclerosis, diabetes mellitus, dyslipidemia renal failure metabolic syndrome stroke myocardial infarction erectile dysfunction neurodegenerative diseases cognitive disorders retinal degeneration uveoretinitis and vascular retinopathy.
Experimentally, BPIFB4 protein or fragment is administered intravenously into a subject in need. Alternatively, its mutation can be delivered subcutaneously, intraocularly, or retroocularly to reach target tissues that need it.

Is Bpifb4 the Key to Longevity?

Is Bpifb4 the Key to Longevity?

What Makes Nanog the Key to Longevity?

Nanog is a transcription factor involved in cell proliferation, differentiation and senescence. It regulates self-renewal and pluripotency of stem cells as well as being an important player in tumorigenesis and metastasis processes. Nanog’s functions include controlling cell cycle progression, chromatin remodeling DNA methylation as well as microRNA expression; its presence has also been shown to correlate to poor prognosis in many cancer types.
Nanog and Oct4 interact to regulate pluripotency in embryonic stem cells (ESCs) via EMT gene repression. Furthermore, Nanog has been demonstrated as a critical player in reprogramming human fibroblasts into induced pluripotent stem cells (iPSCs), while also helping reduce gene transcriptional noise via regulation of polycomb complexes, DNA methylation, and expression of miRNAs.
Nanog gene products can be found both in normal cells and cancer cells, where it appears enriched in putative cancer stem cells (CSCs), with increased levels of senescence markers and other factors that promote cell division, proliferation, and invasion. Knockdown of this gene in gastric cancer cells led to reduced proliferation, migration, as well as decreased expression levels for E-cadherin, caveolin-1, FOXO3a/FOXJ1 genes as well as S-phase genes30.
Nanog is emerging as an indicator of poor prognosis for lung adenocarcinoma (LAC) and pancreatic cancers (APC). A cohort study with 80 LAC patients used tissue microarray analysis to measure protein expression levels of Nanog, Oct4, Klf4, Slug and others. When factored into multivariate models, high levels were associated with worse prognosis; similarly in pancreatic cells high expression of this gene was related with an epithelial-like phenotype while low vimentin and TWIST expression; thus suggesting Nanog may serve as a novel biomarker in addition to conventional diagnosis in auxiliary diagnostic tools to predict poor prognosis.

What Makes Nanog the Key to Longevity?

What Makes Nanog the Key to Longevity?

Can Sirt6 Really Keep Your Heart Young?

SIRT6 is an multifaceted enzyme, deacetylating proteins and stimulating mono-ADP-ribosylation for cell health and genomic stability. Additionally, it binds and stabilizes telomeric chromatin to protect against DNA damage and premature cell senescence; further maintaining heterochromatin at LINE-1 retroelements to suppress transcription while preventing retrotransposition; however it becomes significantly decreased with age, contributing to genome instability and cell senescence; it has even been found down-regulated with age, contributing towards genome instability and cell senescence – thus prompting researchers to investigate if activating SIRT6 activity could reduce or delay its effects by activating its activity.
SIRT6 acts on numerous protein substrates that play key roles in numerous pathways, including hepatic glucose homeostasis, DNA repair and cell cycle regulation. Furthermore, its function is further complicated by its ability to catalyze long-chain acyl group deacylation independent of acetylation or lysine methylation; yet no definitive explanation has been offered regarding this activity.
Utilizing liver RNA from 4h-fasted WT and SIRT6-tg mice, we found that glucose-6-phosphate (G6P) abundance decreased with age in WT mice but was restored back to young-like levels in SIRT6-tg mice (Fig. 3a). This finding could be explained by restoration of GNG levels; SIRT6 thus may block any declines in glucose production associated with age (Supplementary Fig 5b). PCA analysis on significant metabolites revealed significant age-related differences between transgenic and wild-type mice, with genotype accounting for most variance (Supplementary Fig 5a).
We further demonstrated that centenarians possess a variant of SIRT6 (SIRT6K33R/Q) that confers enhanced mADPr activity and enhances interaction with Lamin A/C (LMNA), suggesting they possess improved genome maintenance by way of enhanced methylation of LMNA, mutations of which cause many genetic syndromes, including Hutchinson-Gilford progeria syndrome (HGPS) which causes early-onset premature aging disorder.
SIRT6 plays an essential role in controlling apoptosis and inflammation responses as well as its chromatin-modifying activities, so understanding its role is of crucial importance in human physiology. Our findings show how important SIRT6 may be for cell longevity as a biomarker of aging.

Can Sirt6 Really Keep Your Heart Young?

Can Sirt6 Really Keep Your Heart Young?

Can the Sirt1 gene really slow down heart aging?

SIRT1 is an important protein which removes acetyl groups from proteins, as acetylation can inhibit their function and lead to chronic health issues. Furthermore, this gene works in concert with NAD+ and requires it for its proper functioning; SIRT1’s deficiency has been linked with atherosclerosis and cardiovascular disease among other chronic ailments.
Studies conducted in vivo have demonstrated that SIRT1 expression declines within human atherosclerotic lesions, leading to reduced endothelial function and inflammation as well as an increase in oxidative stress and foam cells formation. Repression of SIRT1 has also been linked to metabolic disorders like diabetes and obesity.
SIRT1 is an established longevity factor, regulating key molecular pathways across bacteria, archaea and eukaryotes. Its chromatin-modifying activity contributes to global transcriptional changes associated with energy metabolism changes as we age as well as stress resistance. SIRT1 plays an integral part in metabolic and homeostatic processes such as gluconeogenesis, fatty acid oxidation, oxidative phosphorylation, the urea cycle and endothelium homeostasis.
Recently, it has been found that nuclear and mitochondrial sirtuins interact to influence various aspects of cell physiology. For example, nuclear SIRT1 and SIRT6 work synergistically to recognize DNA breaks and enhance DDR repair; additionally they play an essential role in reprogramming metabolic and bioenergy processes during inflammation – perhaps this interaction explains why caloric restriction lengthens lifespan?
Research exploring the role of sirtuins in human longevity is expanding quickly. SIRT1 and SIRT6 in particular have been implicated in controlling senescence, cancer and CVD; both genes lie at the core of an intricate molecular circuitry which regulates metabolism, senescence and heterochromatin stability.

Can the Sirt1 gene really slow down heart aging?

Can the Sirt1 gene really slow down heart aging?

Be sure to read our other related stories at GettingOlderNews to learn more about aging and anti-aging.