Evidence-Based Longevity

Redefine How You Age.

Alpine Research delivers clinically-informed anti-ageing protocols grounded in peer-reviewed science. Our comprehensive longevity framework is designed for individuals seeking a systematic, evidence-based approach to cellular health and biological age reduction.

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Cellular Biology

73%

Average reduction in oxidative stress markers observed in NAD⁺ supplementation trials (Yoshino et al., 2021)

Epigenetics

2.5×

Increased autophagy activity associated with caloric restriction and mTOR pathway modulation (López-Otín et al., 2023)

Longevity Research

Hallmarks of ageing identified in landmark research, each addressable through targeted intervention (López-Otín et al., 2023)

The Framework

A Systematic Approach
to Biological Age Reversal

Our protocol addresses the nine hallmarks of ageing through a multi-layered intervention strategy, combining nutritional biochemistry, hormetic stress, and targeted supplementation.

Module 01

Cellular NAD⁺ Restoration

NAD⁺ levels decline approximately 50% between the ages of 40 and 60. Our protocol outlines evidence-based strategies to restore intracellular NAD⁺ through precursor supplementation, dietary intervention, and sirtuin pathway activation.

Module 02

Senescent Cell Clearance

Cellular senescence — the accumulation of non-dividing, pro-inflammatory cells — is a primary driver of tissue dysfunction. This module covers the emerging science of senolytics and dietary compounds shown to facilitate senescent cell clearance in preclinical models.

Module 03

Autophagy Optimisation

Autophagy is the body's intracellular recycling mechanism, critical for removing damaged organelles and misfolded proteins. Our protocol details fasting strategies, mTOR modulation, and nutritional cofactors that upregulate autophagic flux.

Module 04

Mitochondrial Biogenesis

Mitochondrial dysfunction underlies fatigue, cognitive decline, and metabolic disease. This module covers PGC-1α activation through exercise protocols, cold exposure, and targeted nutritional support to stimulate new mitochondrial production.

Module 05

Epigenetic Reprogramming

Epigenetic clocks — measurable markers of biological age — can be influenced through targeted intervention. This module examines the science of DNA methylation patterns, histone modification, and lifestyle factors that modulate epigenetic age.

Module 06

Inflammation & Oxidative Stress

Chronic low-grade inflammation — "inflammageing" — is a hallmark of biological ageing. Our protocol maps the key inflammatory pathways and oxidative stress mechanisms involved, alongside dietary and lifestyle interventions shown to reduce systemic inflammation.

Foundational Research

Grounded in Peer-Reviewed Science

Every recommendation within our protocol is derived from published, peer-reviewed research. We reference primary literature and systematic reviews, not opinion or anecdote.

Epigenetics

The Hallmarks of Ageing: An Expanding Universe

A landmark 2023 update to the foundational hallmarks framework identified nine core mechanisms of biological ageing, including genomic instability, telomere attrition, epigenetic alterations, and loss of proteostasis. Each represents a distinct but interconnected target for longevity intervention.

López-Otín et al. (2023). Cell, 186(2), 243–278.

NAD⁺ Biology

NAD⁺ Metabolism and Its Role in Cellular Senescence

Declining NAD⁺ concentrations with age impair sirtuin activity, mitochondrial function, and DNA repair capacity. Preclinical and early clinical studies demonstrate that restoring NAD⁺ levels via NMN and NR supplementation reverses several age-associated phenotypes in animal models.

Yoshino et al. (2021). Science, 374(6571), eabe9985.

Senolytics

Targeting Senescent Cells to Improve Healthspan

Accumulation of senescent cells drives the secretion of pro-inflammatory cytokines, chemokines, and proteases — collectively termed the senescence-associated secretory phenotype (SASP). Emerging research demonstrates that selective elimination of senescent cells extends median healthspan in murine models.

Kirkland & Tchkonia (2020). EBioMedicine, 58, 102911.

Autophagy

Autophagy and the Ageing Process: Mechanistic Insights

Autophagic flux declines with age, resulting in accumulation of damaged proteins and dysfunctional organelles. Studies in model organisms demonstrate that enhancing autophagy through caloric restriction, rapamycin, and spermidine supplementation consistently extends lifespan and improves late-life health outcomes.

Hansen et al. (2018). Cell, 161(7), 1563–1575.

The Protocol

The Alpine Longevity Protocol

A comprehensive, research-backed framework covering every major dimension of biological ageing. Designed for individuals who approach their health with the rigour of a scientist.

Six core modules covering NAD⁺ restoration, senolytic strategies, autophagy, mitochondrial health, epigenetics, and systemic inflammation

Biomarker tracking framework with reference ranges, testing cadence, and interpretation guidance

Supplementation stack with dosing rationale derived from clinical and preclinical literature

Nutritional and lifestyle protocols with mechanistic explanations grounded in longevity biology

Full reference library linking every recommendation to primary scientific literature

Research Protocol

The Alpine Longevity Protocol

A complete evidence-based framework for reducing biological age and extending healthspan. For research and educational purposes.

Six comprehensive research modules
Biomarker tracking framework
Full supplementation reference guide
Nutritional intervention protocols
Exercise and hormesis framework
Complete scientific reference library
Lifetime access and future updates

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Research Journal

Latest from the Lab

Evidence-based articles on longevity science, ageing biology, and cellular health.

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NAD⁺ Biology

The Science of NAD⁺ Decline and Why It Matters After 40

Intracellular NAD⁺ concentrations fall by roughly half between the ages of 40 and 60. Here is what the research says about why this happens and what can be done about it.

8 min read · March 2026

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Senolytics

Senescent Cells: The Ageing Driver You Have Never Heard Of

Cellular senescence is one of the most actionable hallmarks of biological ageing. Understanding the SASP and its systemic effects is essential to any serious longevity protocol.

10 min read · February 2026

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Mitochondria

Mitochondrial Decline: Why Your Energy Drops With Age and How to Reverse It

Mitochondrial dysfunction is a central feature of ageing. Emerging research demonstrates that targeted interventions can restore mitochondrial number, efficiency, and function.

9 min read · January 2026

The Science of NAD⁺ Decline and Why It Matters After 40

Nicotinamide adenine dinucleotide (NAD⁺) is a coenzyme found in every living cell. It plays a central role in energy metabolism, DNA repair, gene expression, and the regulation of cellular stress responses. Despite its fundamental importance, NAD⁺ concentrations decline dramatically with age — falling by approximately 50% between the fourth and sixth decades of life.

Why Does NAD⁺ Decline?

Several mechanisms contribute to age-related NAD⁺ depletion. First, the enzyme CD38 — a key NAD⁺ consumer — becomes increasingly active with age and chronic inflammation. CD38-driven NAD⁺ consumption is exacerbated by the accumulation of senescent cells, which secrete pro-inflammatory cytokines that further upregulate CD38 activity. Second, the biosynthetic pathways that regenerate NAD⁺ from dietary precursors become less efficient with age, reducing the cell's capacity to replenish its NAD⁺ pool.

Downstream Consequences of NAD⁺ Decline

Falling NAD⁺ levels compromise the activity of sirtuins — a family of NAD⁺-dependent deacylases that regulate mitochondrial biogenesis, genomic stability, and inflammation. SIRT1 and SIRT3, in particular, require adequate NAD⁺ to function, and their declining activity contributes to reduced autophagy, impaired mitochondrial function, and accelerated epigenetic ageing. PARP enzymes — which coordinate DNA damage repair — are also NAD⁺-dependent, meaning lower NAD⁺ availability directly reduces the cell's capacity to respond to genotoxic stress.

Restoring NAD⁺: What the Evidence Shows

The two most studied NAD⁺ precursors are nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR). Both are converted to NAD⁺ via the salvage pathway and have demonstrated the ability to raise intracellular NAD⁺ concentrations in human clinical trials. A 2021 study by Yoshino et al. published in Science demonstrated that NMN supplementation improved skeletal muscle insulin sensitivity and increased NAD⁺ metabolome levels in postmenopausal women with prediabetes. While human data remain early-stage, the mechanistic rationale for NAD⁺ precursor supplementation is well-supported by both cell and animal research.

References: Yoshino et al. (2021). Science, 374(6571). · Cantó et al. (2012). Cell Metabolism, 15(6), 838–847. · Camacho-Pereira et al. (2016). Cell Metabolism, 23(6), 1127–1139.

Senescent Cells: The Ageing Driver You Have Never Heard Of

Cellular senescence is a state of stable cell cycle arrest — a mechanism by which damaged or dysfunctional cells are prevented from dividing. While initially conceived as a tumour suppression mechanism, it is now understood that the accumulation of senescent cells over time is a primary contributor to tissue dysfunction, chronic inflammation, and age-related disease.

The Senescence-Associated Secretory Phenotype

Senescent cells do not simply arrest — they become metabolically hyperactive, secreting a complex mixture of pro-inflammatory cytokines, chemokines, growth factors, and proteases collectively termed the senescence-associated secretory phenotype (SASP). The SASP disrupts the local tissue microenvironment, impairs the function of neighbouring healthy cells, and contributes to systemic chronic inflammation. Over time, this inflammatory milieu accelerates the senescence of additional cells, creating a self-reinforcing cycle that drives biological ageing.

How Senescent Cells Accumulate

Senescence is triggered by a range of stressors including telomere shortening, DNA damage, oxidative stress, and oncogene activation. In youth, the immune system efficiently identifies and clears senescent cells through a process of immune surveillance. With age, this clearance mechanism becomes less effective, allowing senescent cells to accumulate in tissues including adipose tissue, the liver, the lung, and the cardiovascular system.

The Case for Senolytic Intervention

Senolytics are compounds that selectively induce apoptosis in senescent cells while leaving healthy cells unaffected. In murine models, periodic senolytic treatment using dasatinib and quercetin has been shown to extend median lifespan, improve physical function, and reduce markers of systemic inflammation. Fisetin — a natural flavonoid found in strawberries — has also demonstrated senolytic activity in preclinical models and is currently under clinical investigation. While human data for senolytics remains in its early stages, the preclinical evidence is compelling and the mechanistic rationale is well established.

References: Kirkland & Tchkonia (2020). EBioMedicine, 58, 102911. · Xu et al. (2018). Nature Medicine, 24, 1246–1256. · Yousefzadeh et al. (2018). EBioMedicine, 36, 18–28.

Mitochondrial Decline: Why Your Energy Drops With Age and How to Reverse It

Mitochondria are the primary site of cellular energy production, generating adenosine triphosphate (ATP) through oxidative phosphorylation. Beyond energy metabolism, mitochondria regulate calcium homeostasis, reactive oxygen species (ROS) production, and apoptotic signalling. Their functional integrity is critical to virtually every physiological process — and their progressive decline with age is a central feature of biological ageing.

The Hallmarks of Mitochondrial Ageing

Three core features characterise mitochondrial dysfunction in ageing. First, mitochondrial biogenesis — the process of generating new mitochondria — declines with age, partly due to reduced PGC-1α activity, the master regulator of mitochondrial biosynthesis. Second, mitophagy — the selective autophagy of damaged mitochondria — becomes less efficient, allowing dysfunctional mitochondria to accumulate and generate excessive ROS. Third, mitochondrial membrane potential decreases, reducing the efficiency of the electron transport chain and ATP synthesis.

Upstream Drivers of Mitochondrial Decline

Declining NAD⁺ levels — as discussed separately — directly impair mitochondrial function by reducing SIRT3 activity, a mitochondria-localised deacylase that regulates multiple components of the electron transport chain and antioxidant defence. Accumulated mitochondrial DNA mutations, driven by decades of ROS exposure, also degrade mitochondrial respiratory capacity over time. Chronic inflammation further suppresses PGC-1α expression, creating a bidirectional relationship between mitochondrial dysfunction and systemic inflammageing.

Evidence-Based Strategies for Mitochondrial Restoration

High-intensity interval training (HIIT) and resistance exercise are the most potent stimuli for mitochondrial biogenesis, activating PGC-1α through AMPK and p38 MAPK signalling. Cold exposure activates brown adipose tissue and induces mitochondrial uncoupling, a hormetic stressor that promotes mitochondrial efficiency. At a nutritional level, urolithin A — a gut microbiome metabolite of ellagitannins — has demonstrated the ability to restore mitophagy and improve mitochondrial function in human clinical trials. Coenzyme Q10 and PQQ are also frequently studied in the context of mitochondrial support, with evidence supporting a role in electron transport chain efficiency and mitochondrial biogenesis respectively.

References: López-Otín et al. (2023). Cell, 186(2), 243–278. · Ryu et al. (2016). Nature Medicine, 22, 879–888. · Andreux et al. (2019). Nature Metabolism, 1, 595–603.

Redefine How You Age.

A Systematic Approachto Biological Age Reversal

Cellular NAD⁺ Restoration

Senescent Cell Clearance

Autophagy Optimisation

Mitochondrial Biogenesis

Epigenetic Reprogramming

Inflammation & Oxidative Stress

Grounded in Peer-Reviewed Science

The Hallmarks of Ageing: An Expanding Universe

NAD⁺ Metabolism and Its Role in Cellular Senescence

Targeting Senescent Cells to Improve Healthspan

Autophagy and the Ageing Process: Mechanistic Insights

The Alpine Longevity Protocol

The Alpine Longevity Protocol

Latest from the Lab

The Science of NAD⁺ Decline and Why It Matters After 40

Senescent Cells: The Ageing Driver You Have Never Heard Of

Mitochondrial Decline: Why Your Energy Drops With Age and How to Reverse It

The Science of NAD⁺ Decline and Why It Matters After 40

Why Does NAD⁺ Decline?

Downstream Consequences of NAD⁺ Decline

Restoring NAD⁺: What the Evidence Shows

Senescent Cells: The Ageing Driver You Have Never Heard Of

The Senescence-Associated Secretory Phenotype

How Senescent Cells Accumulate

The Case for Senolytic Intervention

Mitochondrial Decline: Why Your Energy Drops With Age and How to Reverse It

The Hallmarks of Mitochondrial Ageing

Upstream Drivers of Mitochondrial Decline

Evidence-Based Strategies for Mitochondrial Restoration

Begin Your Longevity Journey

A Systematic Approach
to Biological Age Reversal